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Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase
Open accessAbstract
Aims/hypothesis Brain-derived neurotrophic factor (BDNF) is produced in skeletal muscle, but its functional significance is unknown. We aimed to determine the signalling processes and metabolic actions of BDNF.Methods We first examined whether exercise induced BDNF expression in humans. Next, C2C12 skeletal muscle cells were electrically stimulated to mimic contraction. L6 myotubes and isolated rat extensor digitorum longus muscles were treated with BDNF and phosphorylation of the proteins AMP-activated protein kinase (AMPK) (Thr(172)) and acetyl coenzyme A carboxylase beta (ACCbeta) (Ser(79)) were analysed, as was fatty acid oxidation (FAO). Finally, we electroporated a Bdnf vector into the tibialis cranialis muscle of mice.Results BDNF mRNA and protein expression were increased in human skeletal muscle after exercise, but muscle-derived BDNF appeared not to be released into the circulation. Bdnf mRNA and protein expression was increased in muscle cells that were electrically stimulated. BDNF increased phosphorylation of AMPK and ACCbeta and enhanced FAO both in vitro and ex vivo. The effect of BDNF on FAO was AMPK-dependent, since the increase in FAO was abrogated in cells infected with an AMPK dominant negative adenovirus or treated with Compound C, an inhibitor of AMPK. Electroporation of a Bdnf expression vector into the tibialis cranialis muscle resulted in increased BDNF protein production and tropomyosin-related kinase B (TrkB(Tyr706/707)) and extracellular signal-regulated protein kinase (p44/42 Thr(202)/Tyr(204)) phosphorylation in these muscles. In addition, phosphorylation of ACCbeta was markedly elevated in the Bdnf electroporated muscles.Conclusions/interpretation These data identify BDNF as a contraction-inducible protein in skeletal muscle that is capable of enhancing lipid oxidation in skeletal muscle via activation of AMPK.
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TL;DR
BDNF is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via AMPK activation in vitro and ex vivo, but muscle-derived BDNF is not released into the circulation and likely acts locally. Human exercise increased muscle BDNF protein about 50% at 24 h recovery, while serum BDNF rose immediately after exercise and tracked platelet counts.
Key findings
- In eight healthy men, 120 min of bicycle exercise at 60% V̇O₂max increased skeletal muscle BDNF protein about 50% at 24 h recovery (p<0.05); BDNF mRNA showed marked inter-individual variation, with an AUC difference between exercise and resting groups (p<0.05).
- Serum BDNF increased immediately after exercise and returned to pre-exercise levels by 60 min; platelet counts followed a closely matching pattern, suggesting the early circulating BDNF increase may at least partly reflect release from activated platelets rather than muscle.
- Electrically stimulated C2C12 myotubes increased Bdnf mRNA and pro- and mature BDNF protein, with no detectable BDNF release into media.
- BDNF increased phosphorylation of AMPK (Thr172) and ACCβ (Ser79) and enhanced palmitate oxidation in L6 myotubes and rat extensor digitorum longus muscle ex vivo; the FAO increase was AMPK-dependent, as it was abrogated by Compound C or an AMPK dominant negative adenovirus. BDNF did not increase glucose uptake (fold change from vehicle: vehicle=1±0.04; insulin 100 nmol/l=2.32±0.072; BDNF 10 ng/ml=0.94±0.071; insulin+BDNF=1.99±0.185).
Methods
- Human in vivo: 8 healthy, physically active but untrained men (mean±SD age 25±4 years, weight 82±8 kg, height 181±1 cm, BMI 25±2 kg/m²) performed 120 min bicycle exercise at 60% V̇O₂max; vastus lateralis biopsies and serum were collected before, immediately after, and at 3, 5, 8, 24, 48, and 72 h recovery.
- Cell culture: differentiated C2C12 myotubes were electrically stimulated for 120 min (18 V; 1 Hz; 24 ms); L6 myotubes were treated with recombinant human BDNF at 1, 10, and 100 ng/ml for 10 and 30 min, with palmitate oxidation and glucose uptake measured, and AMPK inhibition via 40 µmol/l Compound C or dominant negative AMPK adenovirus.
- Ex vivo and in vivo: rat extensor digitorum longus strips were treated with BDNF for palmitate oxidation and AMPK/ACCβ phosphorylation; 8- to 10-week-old C57BL6/C mice underwent intramuscular electroporation of a Bdnf vector into tibialis cranialis with doxycycline induction, with n=3 mice per group. Statistics included two-way ANOVA for repeated measures, unpaired t test for AUCs, and paired t tests for cell culture experiments from three independent experiments.
Limitations
- Stated: the contraction-induced increase in BDNF both in vivo and in vitro was relatively modest, whereas electroporation increased BDNF several fold, so whether BDNF plays an important role in vivo is unclear.
- Stated: whether the ACCβ phosphorylation effect after BDNF overproduction is due to paracrine/autocrine signaling or a direct intracellular signaling event requires further clarification.
- Stated: BDNF plays no role in mediating contraction-induced increases in fat oxidation, because fat oxidation increases at the onset of contraction while muscle BDNF increases well into recovery. Evident: the human exercise cohort was small (n=8), and the paper reports no direct measurement of autocrine/paracrine BDNF action within muscle.
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37 Own result · 16 Own interpretation · 15 Not checked yet · 1 Own method
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In the paper
“We also showed that contraction did not increase LDH release from cells into the media (Fig. 3b).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
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“There were no differences in BDNF mRNA levels in the exercise cohort compared with the resting cohort (Fig. 1a).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
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In the paper
“Irrespective of whether cells were treated with PBS (Fig. 4d) or infected with a control virus (AdGO) (Fig. 4e) treatment of cells with BDNF enhanced fat oxidation.”
- Also stated in: § Abstract · plain
“BDNF increased phosphorylation of AMPK and ACCβ and enhanced FAO both in vitro and ex vivo.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > BDNF increases fat oxidation in an AMPK-dependent manner in L6 myotubes
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In the paper
“BDNF increased phosphorylation of AMPK and ACCβ and enhanced FAO both in vitro and ex vivo.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Abstract
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In the paper
“We were unable to detect any differences in BDNF release in the media of control compared with contraction-treated cells (data not shown).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
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In the paper
“In addition, the plasma levels of P-selectin, a marker of platelet activation, were also increased immediately following exercise (data not shown).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
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In the paper
“The effect of BDNF on FAO was AMPK-dependent, since the increase in FAO was abrogated in cells infected with an AMPK dominant negative adenovirus or treated with Compound C, an inhibitor of AMPK.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Abstract
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- Rests on an assumption: AMPK phosphorylation of ACCβ inhibits ACC, lowers malonyl-CoA, relieves CPT1 inhibition, and increases fatty acid oxidation.
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In the paper
“The time-dependent effects were transient as no differences were seen in phospho-AMPK or phospho-ACCβ at 30 min (data not shown), with the effects present at only 10 min (Fig. 4a-c).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > BDNF increases fat oxidation in an AMPK-dependent manner in L6 myotubes
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In the paper
“To confirm that this increase in BDNF expression was indeed increased within muscle fibres, we performed IHC experiments and showed that the increased BDNF production 24 h after exercise was indeed intramyocellular (Fig. 1d).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
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- Rests on an assumption: The BDNF antibody used recognizes both pro- and mature forms of BDNF.
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In the paper
“In addition, muscle contraction increased Bdnf mRNA levels compared with non-contracted cells (Fig. 3d).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
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“We showed that at the two higher doses, BDNF markedly phosphorylated ACCβ, while a similar effect was seen for phospho-AMPK at the higher dose.”
- Also stated in: § BDNF increases fat oxidation in an AMPK-dependent manner in L6 myotubes · plain
“The lack of effect of phospho-AMPK at 10 ng/ml was unexpected since phospho-ACCβ was increased.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > BDNF increases fat oxidation in an AMPK-dependent manner in L6 myotubes
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“we first showed that PCr, but not ATP, stores were decreased by contraction (Fig. 3a).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
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“Moreover, such a treatment increased both the pro-and mature BDNF protein levels immediately after the contraction protocol (Fig. 3e, f).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: The BDNF antibody used recognizes both pro- and mature forms of BDNF.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We showed that at the two higher doses, BDNF markedly phosphorylated ACCβ, while a similar effect was seen for phospho-AMPK at the higher dose.”
- Also stated in: § BDNF increases fat oxidation in an AMPK-dependent manner in L6 myotubes · plain
“with the effects present at only 10 min (Fig. 4a-c).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > BDNF increases fat oxidation in an AMPK-dependent manner in L6 myotubes
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- Also stated in: § BDNF increases fat oxidation in an AMPK-dependent manner in L6 myotubes · plain
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In the paper
“Serum BDNF concentrations increased immediately following exercise, before returning to pre-exercise levels 60 min following the cessation of exercise (Fig. 2a).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
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“BDNF mRNA and protein expression were increased in human skeletal muscle after exercise, but muscle-derived BDNF appeared not to be released into the circulation.”
- Also stated in: § Results · plain
“As such, we calculated the AUC over time for both groups and showed a difference (p<0.05) for the AUC when comparing the two groups.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Abstract
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“At 24 h into recovery from exercise, BDNF protein levels were increased (about 50%; p<0.05) in the muscle homogenates (Fig. 1b, c).”
- Also stated in: § Abstract · hedged
“BDNF mRNA and protein expression were increased in human skeletal muscle after exercise, but muscle-derived BDNF appeared not to be released into the circulation.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Abstract · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“BDNF increases phosphorylation of AMPK and its downstream target ACCβ and results in enhanced fat oxidation”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > BDNF increases phosphorylation of AMPK and its downstream target ACCβ and results in enhanced fat oxidation
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“It should also be noted that while both BDNF and the positive control 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) increased 14 C in the CO 2 fraction, this was not seen in the acid soluble metabolite fraction, indicating complete oxidation of the label.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > BDNF increases phosphorylation of AMPK and its downstream target ACCβ and results in enhanced fat oxidation
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“By conducting muscle cell culture experiments, we show that C2C12 murine cells not only produce BDNF, but that this production can be increased by contraction.”
- Also stated in: § BDNF increases fat oxidation in an AMPK-dependent manner in L6 myotubes · plain
“Bdnf mRNA and protein expression is increased in contracting muscle cells.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
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In the paper
“However, when cells were treated with the AMPK inhibitor Compound C or infected with an AMPK dominant negative adenovirus, the BDNF-induced increase in fat oxidation was completely abrogated (Fig. 4d, e)”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > BDNF increases fat oxidation in an AMPK-dependent manner in L6 myotubes
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In the paper
“It must be acknowledged, however, that the contraction-induced increase in BDNF both in vivo (Fig. 1) and in vitro (Fig. 3) was relatively modest, whereas we increased BDNF several fold with electroporation (Fig. 6).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
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In the paper
“BDNF increases phosphorylation of AMPK and its downstream target ACCβ and results in enhanced fat oxidation”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > BDNF increases phosphorylation of AMPK and its downstream target ACCβ and results in enhanced fat oxidation
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, we were unable to detect any BDNF in the media from cells that underwent contraction, even though such an intervention increased BDNF protein production.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
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In the paper
“We showed that circulating levels of BDNF increased immediately after exercise and did not correlate with the elevated muscle-derived BDNF 24 h after exercise.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
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“Since platelets are known to store and release BDNF [35], we examined the relationship between circulating BDNF and platelet count.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
What the sources say
- Not checked yetcites [35] Fujimura H, Altar CA, Chen R et al (2002) Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 87:728–734 source
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In the paper
“Recent studies have demonstrated that physical exercise can increase circulating BDNF levels in both healthy humans [19,20] and patients with multiple sclerosis [21], although the cellular origin of this increase is unclear.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Introduction
What the sources say
- Not checked yetcites [19] Ferris LT, Williams JS, Shen CL (2007) The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med Sci Sports Exerc 39:728–734 source
- Not checked yetcites [20] Rojas Vega S, Strüder HK, Vera Wahrmann B, Schmidt A, Bloch W, Hollmann W (2006) Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans. Brain Res 1121:59–65 source
- Not checked yetcites [21] Gold SM, Schulz KH, Hartmann S et al (2003) Basal serum levels and reactivity of nerve growth factor and brain-derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls. J Neuroimmunol 138:99–105 source
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In the paper
“However, in a recent study, Bdnf mRNA was shown to be expressed in murine skeletal muscle and was increased by inhibition of histone deacetylases [24].”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Introduction
What the sources say
- Not checked yetcites [24] Avila AM, Burnett BG, Taye AA et al (2007) Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy. J Clin Invest 117:659–671 source
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In the paper
“The kinetics of the exercise-induced elevation in serum BDNF levels failed to correlate with the increased production of BDNF in muscle 24 h after exercise, suggesting that the skeletal muscle is not a source of the increase in serum BDNF observed early into recovery from exercise.”
- Also stated in: § Abstract · hedged
“but muscle-derived BDNF appeared not to be released into the circulation.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
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In the paper
“Since exercise can inhibit histone deacetylases [25], the possibility exists that the increase in circulating BDNF in humans during exercise may originate in the contracting muscle cells and that BDNF may be a novel contraction-induced myokine.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Introduction
What the sources say
- Not checked yetcites [25] McGee SL, Hargreaves M (2004) Exercise and myocyte enhancer factor 2 regulation in human skeletal muscle. Diabetes 53:1208–1214 source
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In the paper
“It is also known that BDNF reduces food intake and lowers blood glucose in genetically modified (db/db) obese mice [15][16][17][18].”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Introduction
What the sources say
- Not checked yetcites [15][16][17][18]
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these results demonstrate that physical exercise increases circulating BDNF and that the increase may at least to some extent reflect in vivo release of BDNF from activated platelets.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“it is now clear that IL-6 [7] and IL-8 [8] production is upregulated by muscle contraction and that these cytokines may be released from contracting skeletal muscle.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Introduction
What the sources say
- Not checked yetcites [7] Febbraio MA, Pedersen BK (2002) Muscle-derived interleukin-6: mechanisms for activation and possible biological roles. FASEB J 16:1335–1347 source
- Not checked yetcites [8] Pedersen BK, Steensberg A, Fischer C et al (2003) Searching for the exercise factor—is IL-6 a candidate. J Muscle Res Cell Motil 24:113–119 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Recently, we demonstrated a strong association between low plasma BDNF and type 2 diabetes on the one hand and both obesity and insulin resistance on the other [37].”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
What the sources say
- Not checked yetcites [37] Krabbe KS, Nielsen AR, Krogh-Madsen R et al (2007) Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia 50:431–438 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hence, we have identified BDNF as being a novel contraction-induced protein that may contribute to the multiple health benefits associated with exercise, possibly by enhancing fat oxidation in skeletal muscle.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“since we show both in vitro and in intact muscle ex vivo that, like CNTF, BDNF activates AMPK signalling and enhances FAO.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This hypothesis is plausible since overproduction of BDNF resulted in marked ERK (Fig. 6c) and TrkB (Fig. 6d, e) phosphorylation, which is indicative of signalling through TrkB, which is produced in skeletal muscle and myotubes [43].”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: BDNF binding to TrkB causes TrkB phosphorylation and downstream ERK phosphorylation.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, our data demonstrate that BDNF is a protein produced in skeletal muscle cells that is increased by contraction to enhance fat oxidation in an AMPKdependent fashion, most probably by acting in an autocrine and/or paracrine manner within skeletal muscle.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Recent studies have demonstrated that Bdnf mRNA increases in the contracting skeletal muscle of rodents [22,23]”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
What the sources say
- Not checked yetcites [22] Dupont-Versteegden EE, Houlé JD, Dennis RA et al (2004) Exercise-induced gene expression in soleus muscle is dependent on time after spinal cord injury in rats. Muscle Nerve 29:73–81 source
- Not checked yetcites [23] Gómez-Pinilla F, Ying Z, Opazo P, Roy RR, Edgerton VR (2001) Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle. Eur J Neurosci 13:1078–1084 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, we have identified BDNF as being a novel contraction-induced muscle cell-derived protein that can increase fat oxidation in skeletal muscle in an AMPKdependent fashion.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The latter findings are supported by animal studies, which demonstrate an insulin-sensitising effect of BDNF [15][16][17].”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
What the sources say
- Not checked yetcites [15] Ono M, Ichihara J, Nonomura T et al (1997) Brain-derived neurotrophic factor reduces blood glucose level in obese diabetic mice but not in normal mice. Biochem Biophys Res Commun 238:633–637 source
- Not checked yetcites [16] Tonra JR, Ono M, Liu X et al (1999) Brain-derived neurotrophic factor improves blood glucose control and alleviates fasting hyperglycemia in C57BLKS-leprdb/leprdb mice. Diabetes 48:588–594 source
- Not checked yetcites [17] Nakagawa T, Tsuchida A, Itakura Y et al (2000) Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Diabetes 49:436–444 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“As no differences were reported when comparing the muscles of the control with the sham group, data from sham-treated muscles are reported.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Human in vivo experiments
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that BDNF may act in an autocrine and/ or paracrine fashion in skeletal muscle.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
hedgedconditionaln = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Muscle-derived IL-6, but not IL-8, contributes markedly to systemic levels, where it works in a hormone-like fashion and plays an important role in lipid and glucose metabolism [9,10], principally via activation of AMP-activated protein kinase (AMPK) [10].”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Introduction
What the sources say
- Not checked yetcites [9] Febbraio MA, Hiscock N, Sacchetti M, Fischer CP, Pedersen BK (2004) Interleukin-6 is a novel factor mediating glucose homeostasis in skeletal muscle contraction. Diabetes 53:1643–1648 source
- Not checked yetcites [10] Carey AL, Steinberg GR, Macaulay SL et al (2006) Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 55:2688–2697 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“we have recently demonstrated that a different neurotrophin, namely ciliary neurotrophic factor (CNTF) can increase insulin sensitivity and decrease obesity by acting on both central [38] and peripheral [39,40] tissues.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
What the sources say
- Not checked yetcites [38] Steinberg GR, Watt MJ, Fam BC et al (2006) Ciliary neurotrophic factor suppresses hypothalamic AMPK signaling in leptin resistant obese mice. Endocrinology 147:3906–3914 source
- Not checked yetcites [39] Watt MJ, Dzamko N, Thomas W et al (2006) CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat Med 12:541–548 source
- Not checked yetcites [40] Watt MJ, Hevener A, Lancaster GI, Febbraio MA (2006) Ciliary neurotrophic factor prevents acute lipid-induced insulin resistance by attenuating ceramide accumulation and phosphorylation of JNK in peripheral tissues. Endocrinology 147:2077–2085 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“providing further evidence that BDNF exerts its action locally and is not released into the circulation when intramuscular production is increased.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > BDNF increases phosphorylation of AMPK and its downstream target ACCβ and results in enhanced fat oxidation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“in a recent study, the mRNA of Bdnf was shown to be expressed in murine skeletal muscle homogenates and that this was increased by inhibition of histone deacetylases [24]”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
What the sources say
- Not checked yetcites [24] Avila AM, Burnett BG, Taye AA et al (2007) Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy. J Clin Invest 117:659–671 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Results from our human exercise studies and cell culture experiments suggested that BDNF was produced by muscle cells during contraction, but was not released into the circulation or media.”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > BDNF increases phosphorylation of AMPK and its downstream target ACCβ and results in enhanced fat oxidation
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It is well known that pro-BDNF can be processed into mature BDNF by several matrix metalloproteinases and thereby regulate activation of TrkB either by autophosphorylation or via an interaction with a neighbouring cell [44].”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
What the sources say
- Not checked yetcites [44] Ethell IM, Ethell DW (2007) Matrix metalloproteinases in brain development and remodeling: synaptic functions and targets. J Neurosci Res 85:2813–2823 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
AMPK phosphorylation of ACCβ inhibits ACC, lowers malonyl-CoA, relieves CPT1 inhibition, and increases fatty acid oxidation.
“AMPK phosphorylates ACCβ resulting in inhibition of ACC activity, which in turn leads to a decrease in malonyl-CoA content, relieving inhibition of carnitine palmitoyl transferase 1 and increasing fatty acid oxidation (FAO).”
The paper relies on this without support.
The BDNF antibody used recognizes both pro- and mature forms of BDNF.
“The antibody against BDNF protein recognises both the pro-and mature forms of BDNF.”
The paper relies on this without support.
During exercise in humans, fat oxidation increases at the onset of contraction.
“It should be noted that during exercise in humans, fat oxidation is increased at the onset of contraction while the increase in BDNF in skeletal muscle does not occur until well into recovery.”
The paper relies on this without support.
During exercise in humans, the increase in BDNF in skeletal muscle does not occur until well into recovery.
“It should be noted that during exercise in humans, fat oxidation is increased at the onset of contraction while the increase in BDNF in skeletal muscle does not occur until well into recovery.”
The paper relies on this without support.
BDNF binding to TrkB causes TrkB phosphorylation and downstream ERK phosphorylation.
“Upon BDNF binding, TrkB is phosphorylated (Tyr 705/706 ) resulting in a signalling cascade that includes phosphorylation of ERK (Thr 202 /Tyr 204 ).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“BDNF mRNA and protein expression were increased in human skeletal muscle after exercise, but muscle-derived BDNF appeared not to be released into the circulation (332).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [332]
In the citing paper
“In contrast, BDNF is identified as a myokine capable of enhancing AMPK activation and hence lipid oxidation in an autocrine or paracrine manner (63).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [63]
In the citing paper
“Brain-derived neurotrophic factor (BDNF) is also expressed in human skeletal muscles, but BDNF is not released into the circulation and does not work in an endocrine way.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [63]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Results
“Serum BDNF concentrations increased immediately following exercise, before returning to pre-exercise levels 60 min following the cessation of exercise (Fig. 2a).”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Human in vivo experiments
“Muscle biopsy samples were obtained from vastus lateralis before exercise, immediately after exercise, and 3, 5, 8, 24, 48 and 72 h into recovery using a percutaneous needle biopsy technique with suction.Samples were snap frozen before being analysed for BDNF mRNA and protein expression.Serum was obtained at the above mentioned time-points.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Discussion
“Upon BDNF binding, TrkB is phosphorylated (Tyr 705/706 )”
§ Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase > Analytical methods
“phospho-TrkB (Tyr 706/707 )”
Citations
Cites
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Cited by
Sorted by citations
Items 401–500 of 713
Głowacka, A., Ji, B., Szczepankiewicz, A. A., Skup, M., & Gajewska‐Woźniak, O. (2022) · Biomedicines · doi:10.3390/biomedicines10112851 · Cited by 13
“We hypothesize that the BDNF is expressed in muscle fibers during functional improvement, which was observed in this study, since the BDNF is target-derived and expressed in an activity-dependent manner [28,31,32,79].”
BackgroundFatma, R., Chauhan, W., Shahi, M. H., & Afzal, M. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2022.1035885 · Cited by 15
Orioli, L., & Thissen, J. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1554617 · Cited by 17
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“Both unaffected [28, 29], and increased [30, 31] BDNF mRNA expression have been observed in skeletal muscle in the following hours after exercise.”
InfluentialEffects triggered in the periphery by acupuncture
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Skeletal muscle: a novel and intriguing characteristics as a secretory organ
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“In addition to IL-6, other muscle-secreted proteins such as brain-derived neurotrophic factor, fibroblast growth factor 21, IL-15, and myonectin have been shown to be produced in skeletal muscle in response to acute or chronic exercise, and have been suggested to increase fat oxidation or glucose uptake in skeletal mu…”
BackgroundWang, N., Zhu, S., Chen, S., Zou, J., Zeng, P., & Tan, S. (2025) · Reviews in the Neurosciences · doi:10.1515/revneuro-2024-0147 · Cited by 12
Nowicka, M., Górska, M., Edyko, K., Szklarek-Kubicka, M., Adam, K., Prylińska, M., Niewodniczy, M., Kostka, T., & Kurnatowska, I. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11092283 · Cited by 12
“A decreased contraction of skeletal muscles can cause a decline in the secretion of BDNF as well as a volume reduction of the hippocampus and, thus, has been implicated in life satisfaction [45].”
BackgroundGraybeal, A. J., Willis, J. L., Morales, E., Tinsley, G. M., Messiah, S. E., & Shah, M. (2022) · Nutrition · doi:10.1016/j.nut.2022.111815 · Cited by 12
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“BDNF also influences energy metabolism and adipose tissue by enhancing fat oxidation through an AMPK-dependent pathway in skeletal muscles, leading to a reduction in adipose tissue mass [69].”
BackgroundLau, L. Y., Nguyen, L. T., Reverter, A., Moore, S. S., Lynn, A., McBride‐Kelly, L., Phillips-Rose, L. S., Plath, M., Macfarlane, R., Vasudivan, V., et al. (2020) · Veterinary Medicine and Science · doi:10.1002/vms3.278 · Cited by 11
“Again, under exercise, the increased mRNA and protein level of brain-derived neurotrophic factor (BDNF) in skeletal muscle enhances fat oxidation through activation of AMPK (AMP-dependent kinase) signalling (Matthews et al., 2009).”
BackgroundGoode, A. P., Hu, D. G., George, S. Z., Schwartz, T. A., Kraus, V. B., Huebner, J. L., Cleveland, R. J., Taylor, K. A., Jordan, J. M., & Golightly, Y. M. (2022) · Osteoarthritis and Cartilage Open · doi:10.1016/j.ocarto.2022.100270 · Cited by 13
Brain-derived neurotrophic factor, epigenetics in stroke skeletal muscle, and exercise training
Ryan, A. S., Xu, H., Ivey, F. M., et al. (2019) · Neurology Genetics · doi:10.1212/nxg.0000000000000331 · Cited by 12
Brain-derived neurotrophic factor among patients with alcoholism
Martín‐González, C., Romero-Acevedo, L., Fernández-Rodríguez, C. M., Medina-Vega, L., Rodríguez, A. G., Toledo, P. O., Navarrete, L. G., Vera-Delgado, V. E., & González‐Reimers, E. (2020) · CNS Spectrums · doi:10.1017/s1092852920001431 · Cited by 13
“During exercise, muscle BDNF expression also increases, but it is not secreted, being involved in AMPK-dependent fat oxidation, facilitating muscle contraction.(21) In addition to its neurotrophic effect, BDNF protects mitochondria against oxidative damage and exerts antiapoptotic effects.”
BackgroundDonati, F., Sian, V., Biasini, G. M., de la Torre, X., Folchitto, F., & Botrè, F. (2021) · Frontiers in Sports and Active Living · doi:10.3389/fspor.2021.619573 · Cited by 14
Berezovskaya, A. S., Tyganov, S. A., Nikolaeva, S. D., Naumova, A. A., Shenkman, B. S., & Glazova, M. V. (2021) · Life · doi:10.3390/life11050449 · Cited by 12
“It is known that physical exercises stimulate expression and release of neurotrophins, such as brain-derived neurotrophic factor (BDNF), from the muscles into the blood circulation, and thus stimulate hippocampal neurogenesis [17,18].”
BackgroundRed foxtail millet upregulates brain-derived neurotrophic factor levels in vitro and in vivo
NAKAJIMA, K., TOMOHIRO, H., & Oiso, S. (2023) · Biomedical Research · doi:10.2220/biomedres.44.97 · Cited by 11
Zhang, Z., Wu, H., Wang, S., Li, Y., Yang, P., Xu, L., Liu, Y., & Liu, M. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155671 · Cited by 11
Katz, D. H., Lindholm, M. E., & Ashley, E. A. (2024) · Physiology · doi:10.1152/physiol.00024.2024 · Cited by 12
Ohko, H., Umemoto, Y., Sakurai, Y., Araki, S., Kojima, D., Kamijo, Y., Murai, K., Yasuoka, Y., & Tajima, F. (2021) · International Journal of Hyperthermia · doi:10.1080/02656736.2021.1922761 · Cited by 11
What Muscle Signals Mediate the Beneficial Effects of Exercise on Cognition?
Benarroch, E. E. (2022) · Neurology · doi:10.1212/wnl.0000000000201049 · Cited by 12
“However, muscle BDNF may have a primary autocrine function and has not yet been shown to be released from the muscle to mediate direct muscle-brain interactions.(66) This indicates that the exercise-induced increase in brain BDNF primarily depends on other signals released from the muscle.”
BackgroundJust‐Borràs, L., Cilleros‐Mañé, V., Polishchuk, A., Balanyà-Segura, M., Tomàs, M., García, N., Tomàs, J. M., & Lanuza, M. A. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1069940 · Cited by 12
“Consequently, TrkB regulates both the postsynaptic and presynaptic components to adapt the neurotransmission mechanism to the requirements of each synapse (Lu, 2003; Mantilla et al., 2004, 2014; Matthews et al., 2009; Garcia et al., 2010a; Santafé et al., 2014; Hurtado et al., 2017a,b; Simó et al., 2018, 2019).”
Backgroundα2-Adrenergic Disruption of β Cell BDNF-TrkB Receptor Tyrosine Kinase Signaling
Kalwat, M. A., Huang, Z., Binns, D. D., McGlynn, K., & Cobb, M. H. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.576396 · Cited by 11
“RTKs share certain signaling pathways; the Ras-ERK1/2, PI3K-Akt and PLCγ pathways are the most recognized (Minichiello, 2009).”
BackgroundMyokines: Do they really exist?
Manabe, Y., Miyatake, S., & Takagi, M. (2012) · The Journal of Physical Fitness and Sports Medicine · doi:10.7600/jpfsm.1.51 · Cited by 11
Johnson, T. K., Belcher, D. J., Sousa, C. A., Carzoli, J. P., Visavadiya, N. P., Khamoui, A. V., WHITEHURST, M. A., & Zourdos, M. C. (2020) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2019-0854 · Cited by 11
“Additionally, both BDNF (in humans) and CatB (in mice) release from skeletal muscle have been triggered by increased AMP activated protein kinase (AMPK) (Matthews et al. 2009; Moon et al. 2016); signaling that exercise should be fatiguing to facilitate this response.”
BackgroundInfluentialHorváth, L., Pekár, M., Švagera, Z., Horká, V., Mráz, M., & Bužga, M. (2025) · Physiological Research · doi:10.33549/physiolres.935751 · Cited by 14
“BDNF is released by skeletal muscle in response to exercise, although muscle-derived BDNF does not appear to be released into the circulation at a high concentration, as increased concentration of BDNF after exercise has been observed mainly in the muscle itself [28].”
Regulation of AMPA receptor trafficking by secreted protein factors
Rennich, B. J., Luth, E. S., Moores, S., & Juo, P. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1271169 · Cited by 10
Mechanisms Underlying the Rarity of Skeletal Muscle Cancers
Kump, D. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126480 · Cited by 10
“Although SKM-specific BDNF expression (both mRNA and protein) increases with exercise in mice [202] and humans, post-exercise plasma levels in humans remain unchanged [203].”
BackgroundBDNF secretion from C2C12 cells is enhanced by methionine restriction
Antony, R. M., & Li, Y. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.10.017 · Cited by 10
“It was shown that muscle-derived BDNF is involved in regulation of metabolism and energy homeostasis[9-11], and muscle regeneration[12].”
BackgroundGrzelak, N., Krutki, P., Bączyk, M., Kaczmarek, D., & Mrówczyński, W. (2023) · Scientific Reports · doi:10.1038/s41598-023-31703-8 · Cited by 12
Reganova, E., Solovyeva, K., Buyanov, D., Gerasimenko, A. Y., & Репин, Д. В. (2023) · Bioengineering · doi:10.3390/bioengineering10050536 · Cited by 10
“Skeletal muscles are known to be some of the sites of BDNF synthesis and accumulation [18].”
BackgroundLiu, T., Li, H., Conley, Y. P., Primack, B. A., Wang, J., & Li, C. (2022) · Biological Research For Nursing · doi:10.1177/10998004211065151 · Cited by 11
“In addition, it is noteworthy that BDNF is also expressed in tissues outside of the central nervous system, such as skeletal muscle cells (Halievski et al., 2020;Matthews et al., 2009).”
BackgroundFaraldi, M., Sansoni, V., Perego, S., Gomarasca, M., Gerosa, L., Ponzetti, M., Rucci, N., Banfi, G., & Lombardi, G. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.915080 · Cited by 10
“In vitro experiments have demonstrated the increase of BDNF in SKM cells where it enhances fatty acid oxidation via AMPK after electric stimulation (Matthews et al., 2009).”
BackgroundInfluence of BDNF polymorphisms on Wilson’s disease susceptibility and clinical course
Mirowska-Guzel, D. M., Litwin, T., Gromadzka, G., Członkowski, A., & Członkowska, A. (2013) · Metabolic Brain Disease · doi:10.1007/s11011-013-9399-x · Cited by 10
“BDNF polymorphisms and course of WD No differences were found in the distributions of the BDNF Val66Met and −270 C/T genotypes between patients with predominant neurological-psychiatric disease and patients with the hepatic form of the disease at diagnosis.”
BackgroundInfluentialSchmalhofer, M., Markus, M. R. P., Gras, J. C., Kopp, J., Janowitz, D., Grabe, H. J., Groß, S., Ewert, R., Gläser, S., Albrecht, D., et al. (2019) · Biomolecules · doi:10.3390/biom9100630 · Cited by 13
“Since BDNF is secreted by contracting skeletal muscle cells, exercise and CRF may influence the synthesis of this neurotrophin [11].”
Garneau, L., Mulvihill, E. E., Smith, S. R., Sparks, L. M., & Aguer, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094889 · Cited by 13
“Many of these myokines modify skeletal muscle metabolism through the AMPK pathway following exercise [20,24,27,28].”
BackgroundInfluentialBalanyà-Segura, M., Polishchuk, A., Just‐Borràs, L., Cilleros‐Mañé, V., Silvera-Simón, C., Ardèvol, A., Tomàs, M., Lanuza, M. A., Hurtado, E., & Tomàs, J. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158018 · Cited by 9
“Alternative splicing generates one TrkB full-length isoform (TrkB-FL), with an intracellular kinase domain, and two truncated isoforms (TrkB-T1 and TrkB-T2) that do not have it [51,52].”
BackgroundGan, J., He, J., Zhou, K., Shang, Z., Dong, G., Bao, D., & Zhou, J. (2024) · Journal of Exercise Science & Fitness · doi:10.1016/j.jesf.2024.12.004 · Cited by 11
Exercise Mimetics in Aging: Suggestions from a Systematic Review
Giacomello, E., Nicoletti, C., Canato, M., & Toniolo, L. (2025) · Nutrients · doi:10.3390/nu17060969 · Cited by 10
“Interestingly, BDNF has been confirmed to be produced by skeletal muscle cells in response to contraction and to induce fat oxidation via the activation of AMPK, with a strict relationship between myokine production and metabolism modulation observed [146].”
Barros‐Aragão, F. G. Q., Januszkiewicz, E., Hunter, T., Silva, N. D. M. L. E., & Felice, F. G. D. (2025) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2025.101189 · Cited by 14
Creatine supplementation and muscle-brain axis: a new possible mechanism?
Ribeiro, F., Forbes, S. C., Candow, D. G., Perim, P., Lira, F. S., Lancha, A. H., & Neto, J. C. R. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1579204 · Cited by 17
Jachim, S. K., Sakamoto, A. E., Zhang, X., Pearsall, V. M., Schafer, M. J., & LeBrasseur, N. K. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101147 · Cited by 12
Neuman, J., Ina, E. A., Huq, S. O., Blanca, A., & Petrosky, S. N. (2024) · Cureus · doi:10.7759/cureus.56343 · Cited by 10
“Additionally, another mechanism by which physical activity can impact memory is via the increase in brain-derived neurotrophic factor (BDNF), which stimulates neuroplasticity throughout the cortex, but most specifically the hippocampus [14].”
BackgroundSuwa, M., Nakano, H., Radak, Z. O., & Kumagai, S. (2014) · The Journal of Physiological Sciences · doi:10.1007/s12576-014-0349-0 · Cited by 9
“Skeletal muscle AMPK is known to be activated by exercise [10, 11]; secretory factors including leptin [12], adiponectin [13], interleukin-6 [14], and brain-derived neurotrophic factor [15]; and antidiabetic drugs [16, 17].”
BackgroundDrewe, J., Boonen, G., & Culmsee, C. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154060 · Cited by 10
A potential research target for cardiac rehabilitation: brain-derived neurotrophic factor
Zou, J., & Hao, S. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1348645 · Cited by 10
Moreno-Infantes, F., Díaz-Quesada, G., Radesca, K., Muñoz-Andradas, G., & Domínguez-Balmaseda, D. (2024) · Physiologia · doi:10.3390/physiologia4040027 · Cited by 9
“This reduction decreases the inhibition of carnitine palmitoyltransferase 1 and subsequently increases fatty acid oxidation [27].”
Exerkines: Potential regulators of ferroptosis
Jia, M., Li, F., Wu, T., & Chen, N. (2025) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2025.101032 · Cited by 10
“119 Nevertheless, other myokines, such as irisin and cathepsin B (CTSB), have been shown to be regulated by exercise and can be released into circulation, thereby crossing the blood-brain barrier and leading to an increase in BDNF level in the brain.”
Bulğay, C., Zorba, E., Kazan, H. H., Bayraktar, I., Uca, M., Ergün, M. A., John, G., Yusupov, R. A., Sultanov, R., Semenova, E. A., et al. (2025) · European Journal of Applied Physiology · doi:10.1007/s00421-025-05804-3 · Cited by 11
“…repair, adaptation, and energy homeostasis by regulating processes like mitochondrial biogenesis and fatty acid oxidation through the activation of AMP-activated protein kinase (AMPK) signaling pathways (Mousavi et al. 2004; Matthews et al. 2009; Pedersen and Febbraio 2012; Rentería et al. 2022).”
Sierra, A., Galán, B. S. M., Zocoler, C. A. S., de Menezes, D. C., Branquinho, J. L. D. O., Neves, R. L., Arata, J. G., Bittencourt, C. A., Barbeiro, H. V., de Souza, H. P., et al. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.919544 · Cited by 15
Tsutsui, Y., Yoshio, S., Tomiyama, T., Shimagaki, T., Itoh, S., Harada, N., Yoshida, Y., Yoshikawa, S., Kakazu, E., Kanto, T., et al. (2022) · Hepatology Research · doi:10.1111/hepr.13834 · Cited by 8
“BDNF is not only derived from the brain but also produced by immune cells and skeletal muscle cells.(13,14) We aimed to clarify the dynamics and impact of BDNF on the prognosis of LDLT patients with immune dysfunction and sar-”
BackgroundIdentification of myokines susceptible to improve glucose homeostasis after bariatric surgery
Orioli, L., Canouil, M., Sawadogo, K. A., Ning, L., Deldicque, L., Lause, P., de Barsy, M., Froguel, P., Loumaye, A., Deswysen, Y., et al. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad122 · Cited by 9
Li, L., Guan, X., Huang, Y., Qu, B., Yao, B., & Ding, H. (2024) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2024.01.005 · Cited by 8
“23 JAK2 is a member of the Janus kinase/signal transduction and transcriptional activation molecule signaling pathway, which is widely involved in physiological processes such as proliferation, differentiation, apoptosis, and in fl ammation.”
BackgroundBrain‐derived neurotrophic factor drives muscle adaptation similar to aerobic training in mice
Brown, A. D., Marko, A. D., Marko, D. M., Baranowski, B. J., Silvera, S., Finch, M. S., Yang, A. J. T., Dhaliwal, R., Ryan, C. R., Roy, B. D., et al. (2025) · The FASEB Journal · doi:10.1096/fj.202402421r · Cited by 11
Fueling Up Skeletal Muscle to Reduce Obesity: A TrkB Story
Youn, J. Y., & Cai, H. “. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2015.03.004 · Cited by 8
Spartano, N. L., Himali, J. J., Trinquart, L., Yang, Q., Weinstein, G., Satizábal, C. L., Dukes, K. A., Beiser, A., Murabito, J. M., Vasan, R. S., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-215109 · Cited by 9
“BDNF can be produced in both the brain and in peripheral tissues, including platelets [57–59], and can cross the blood-brain barrier [60].”
Aktitiz, S., ATAKAN, M. M., Turnagöl, H. H., & Koşar, Ş. N. (2022) · Peptides · doi:10.1016/j.peptides.2022.170864 · Cited by 8
Beyin Kaynaklı Nörotrofik Faktör
Yarım, G. F., & Kazak, F. (2015) · Atatürk Üniversitesi Veteriner Bilimleri Dergisi · doi:10.17094/avbd.02290 · Cited by 8
“Kas hücrelerinde lipid oksidasyonunu uyardığı rapor edilmiştir (52).”
Yoo, J., Lee, B. D., Lee, S. J., Yeul, J., & Kim, M. R. (2017) · European Journal of Lipid Science and Technology · doi:10.1002/ejlt.201700397 · Cited by 8
Decreased Serum Brain-Derived Neurotrophic Factor Concentrations 72 Hours Following Marathon Running
Roeh, A., Holdenrieder, S., Schoenfeld, J., Haeckert, J., Halle, M., Falkai, P., Scherr, J., & Hasan, A. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.668454 · Cited by 8
Azoulay, D., & Horowitz, N. A. (2021) · Blood Reviews · doi:10.1016/j.blre.2021.100871 · Cited by 8
Gökçe, E., Adıgüzel, E., Koçak, Ö. K., Kılınç, H., Langeard, A., Boran, H. E., & Çengiz, B. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.05.032 · Cited by 9
Duan, L., Li, H.-M., Li, S., Shi, Y., & Feng, Y. (2024) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.15045 · Cited by 7
“37 Additionally, studies have demonstrated that the muscle factor irisin can increase BDNF expression in the regions, 38 and brain irisin can affect hippocampal synaptic plasticity and memory preservation in mice, but the impact of irisin on cognitive ability is still controversial.”
Orioli, L., Thissen, J.-P., & Loumaye, A. (2025) · Clinical Nutrition · doi:10.1016/j.clnu.2025.106547 · Cited by 9
Hajhashemy, Z., Lotfi, K., Shahdadian, F., Rouhani, P., Heidari, Z., & Saneei, P. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.980274 · Cited by 7
“BDNF, as a novel contraction-induced muscle cellderived protein, can enhance fat oxidation in skeletal muscle (21).”
BackgroundMontgomery, M. K., Nardo, W. D., & Watt, M. J. (2023) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00178.2023 · Cited by 8
Self-citationBehrendt, T., Quisilima, J. I., Bielitzki, R., Behrens, M., Glazachev, O. S., Brigadski, T., Leßmann, V., & Schega, L. (2024) · Annals of Medicine · doi:10.1080/07853890.2024.2304650 · Cited by 8
“…BDNF. although the origin of BDNF P is not completely understood, potential sources are vascular endothelial [124] and skeletal muscle cells [125], macrophages, lymphocytes [126,127], and, to an substantial extent, neurons and glia cells of the central nervous system [23,24,27]. an…”
BackgroundDiagnostic and predictive abilities of myokines in patients with heart failure
Berezin, O. O., Berezina, T. A., Hoppe, U. C., Lichtenauer, M., & Berezin, A. Е. (2024) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2023.12.021 · Cited by 8
Zhan, Y., Zhang, Z., Lin, S., Du, B., Zhang, K., Wu, J. C., & Xu, H. (2025) · Aging Clinical and Experimental Research · doi:10.1007/s40520-025-02977-x · Cited by 9
“Skeletal muscle secretes myokines, such as brain-derived neurotrophic factor (BDNF), during contraction [57, 58 ].”
Health benefits of physical activity: What role does skeletal muscle-organ crosstalk play?
Powers, S. K., Goldstein, E. R., Lategan-Potgieter, R., Schrager, M. A., Skelton, M., & Demirel, H. A. (2025) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2025.02.010 · Cited by 7
“161 Finally, musclin is another exercise-inducible myokine that has been reported to increase endurance in rodents, in part, by increasing mitochondria biogenesis in skeletal muscle.”
Elia, A., Parodi‐Rullán, R. M., Vázquez‐Torres, R., Carey, A. M., Zhao, H., Javadov, S. A., & Fossati, S. (2026) · Advanced Science · doi:10.1002/advs.202511924 · Cited by 9
“BDNF operates through tropomyosin receptor kinase B (TrkB) stimulation, contributing to the activation of neuronal pro-survival genes, including BDNF itself, through cAMP response element-binding protein (CREB) signaling [ 15 ].”
APP processing: a biochemical competition influenced by exercise-induced signaling mediators?
Marko, D. M., & MacPherson, R. E. K. (2022) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00297.2021 · Cited by 7
ProBDNF Upregulation in Murine Hind Limb Ischemia Reperfusion Injury: A Driver of Inflammation
Aby, K., Antony, R. M., & Li, Y. (2023) · Biology · doi:10.3390/biology12070903 · Cited by 7
Adipokine-myokine-hepatokine compartment-system in mothers and children: An explorative study
Deibert, C., Ferrari, N., Flöck, A., Merz, W. M., Gembruch, U., Lehmacher, W., Ehrhardt, C., & Gräf, C. (2016) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2016.02.002 · Cited by 7
THE ROLE OF MYOKINES INTERSTITIAL INTERACTION AND REGULATION OF METABOLISM: A REVIEW OF LITERATURE
Тамерланович, Ц. Т., White, Z. E., & Rozhinskaya, L. Y. (2016) · Osteoporosis and Bone Diseases · doi:10.14341/osteo2016128-34 · Cited by 7
Nishimura, Y., Nakamura, T., Kamijo, Y., Arakawa, H., Umemoto, Y., Kinoshita, T., Sakurai, Y., & Tajima, F. (2020) · Journal of Spinal Cord Medicine · doi:10.1080/10790268.2020.1816402 · Cited by 7
Skeletal Muscle as Endocrine Organ
Ma, M., Zhang, Z., Hai, B., & Zhang, Y. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-88361-3_22 · Cited by 9
The Dual Role of Myokines in Fatigue Associated with Inflammatory Joint Diseases
Chmielewski, G., Kuna, J., Jaśkiewicz, Ł., Knapik, M., Mikiewicz, M., Majewski, M. S., & Krajewska–Włodarczyk, M. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s545914 · Cited by 9
“42 Skeletal muscles, previously not considered significant in pathogen defense, are now recognized as active participants in immune responses.”
Yoon, J. P., Park, S.-J., Kim, D.-H., Choi, Y., Lee, H., Kim, J.-Y., Cho, C., & Chung, S. W. (2025) · The American Journal of Sports Medicine · doi:10.1177/03635465251369517 · Cited by 7
“20,21,26 Notably, BDNF has been shown to contribute to muscle fiber regeneration and the maintenance of muscle function through its roles in stabilizing the neuromuscular junction (NMJ), preserving motor neuron function, and enhancing synaptic plasticity.”
InfluentialFarhana, F., Sultana, M. A., Hia, R. A., & Hegde, V. K. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106501 · Cited by 8
Beckner, M. E., Conkright, W. R., Mi, Q., Martin, B. J., Sahu, A., Flanagan, S. D., Ledford, A. K., Wright, M., Susmarski, A., Ambrosio, F., et al. (2022) · Physiological Genomics · doi:10.1152/physiolgenomics.00184.2021 · Cited by 6
Exercise training improves long-term memory in obese mice
Fuller, O. K., Egan, C. L., Robinson, T. L., Perera, N., Latchman, H. K., Terry, L. V., McLennan, E. D., Chavez, C. A., Burrows, E. L., Scott, J. W., et al. (2023) · Life Metabolism · doi:10.1093/lifemeta/load043 · Cited by 6
Self-citationTsukada, Y., Nishiyama, Y., Kishimoto, M., Nago, T., Harada, H., Niiyama, H., Katoh, A., Matsuse, H., & Kai, H. (2024) · PLoS ONE · doi:10.1371/journal.pone.0298223 · Cited by 7
Effects of Exercise-Induced Changes in Myokine Expression on the Tumor Microenvironment
Gunasekara, N., Clauss, D., & Bloch, W. (2024) · Sports Medicine International Open · doi:10.1055/a-2283-1663 · Cited by 6
“While the amount and mRNA expression of BDNF is increased in muscle through exercise, the ef - fects appear to be local without release into the bloodstream, which makes an influence on the TME unlikely [25, 112].”
BackgroundWon, C. W., Kim, M., & Shin, H. E. (2024) · The Journals of Gerontology Series A · doi:10.1093/gerona/glae237 · Cited by 8
Paltsyn, A. A. (2020) · Zhurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» · doi:10.25557/0031-2991.2020.01.135-141 · Cited by 6
Soluble Factors Associated with Denervation-induced Skeletal Muscle Atrophy
Rodríguez, M. P., & Cabello‐Verrugio, C. (2023) · Current Protein and Peptide Science · doi:10.2174/0113892037189827231018092036 · Cited by 7
Myokines: A central point in managing redox homeostasis and quality of life
Rathor, R., & Suryakumar, G. (2024) · BioFactors · doi:10.1002/biof.2054 · Cited by 6
“57 Reports have depicted the positive response of BDNF for mitochondrial activity in muscle cells 57 and in metabolically stressed animals.”
Yook, J.-S., & Cho, J. (2017) · Physical Activity and Nutrition · doi:10.20463/jenb.2017.0046 · Cited by 6
Clinical Impact of Circulating Irisin on Classified Coronary Plaque Characteristics
Hirayama, K., Ishii, H., Kikuchi, R., Suzuki, S., Aoki, T., Harada, K., Sumi, T., Negishi, Y., Shibata, Y., Tatami, Y., et al. (2018) · The Journal of Applied Laboratory Medicine · doi:10.1373/jalm.2017.025296 · Cited by 6
Kucera, J., Kučerová, J., Zlámal, F., Kuruczová, D., Babinská, Z., Tomandl, J., Tomandlová, M., & Vašků, J. B. (2019) · Pharmacological Reports · doi:10.1016/j.pharep.2019.03.005 · Cited by 7
Applying the understanding of central sensitization in practice
Wallden, M., & Nijs, J. (2021) · Journal of Bodywork and Movement Therapies · doi:10.1016/j.jbmt.2021.04.004 · Cited by 6
Maroofi, A., Rouch, A. B., Naderi, N., & Damirchi, A. (2022) · IJC Heart & Vasculature · doi:10.1016/j.ijcha.2022.101022 · Cited by 10
Increasing Effect of Citrus natsudaidai on Brain-Derived Neurotrophic Factor
Nakajima, K., Okubo, S., & Oiso, S. (2023) · Journal of Oleo Science · doi:10.5650/jos.ess22324 · Cited by 6
Kang, S., Park, I., & Lim, S. (2020) · doi:10.21203/rs.3.rs-16256/v2 · Cited by 6
Aby, K., Antony, R. M., Yang, T., Longo, F. M., & Li, Y. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26010401 · Cited by 7
“Among the growing list of myokines is brain-derived neurotrophic factor (BDNF) [1,17,18].”
Muscle-brain crosstalk as a driver of brain health in aging
McNeish, B. L., Miljkovic, I., Liu-Ambrose, T. Y. L., Ambrosio, F., Esser, K. A., Fahnestock, M. L., & Rosano, C. (2025) · GeroScience · doi:10.1007/s11357-025-01833-0 · Cited by 10
“While most BDNF research has focused on its endogenous effects on neural plasticity in preclinical models, BDNF is also known to be expressed in muscle in response to exercise [78] and is present in measurable amounts in plasma and serum [79].”
Li, Z., Cui, Z., Wang, T., Zheng, H., Li, K., & Yang, C. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1599980 · Cited by 8
Metadata
- Authors
- Matthews, V. B., Åström, M.-B., Chan, M. H. S., Bruce, C. R., Krabbe, K. S., Prelovsek, O., Åkerström, T., Yfanti, C., Broholm, C., Mortensen, O. H., Penkowa, M., Hojman, P., Zankari, A., Watt, M. J., Bruunsgaard, H., Pedersen, B. K., & Febbraio, M. A.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- University of Copenhagen (DK)
- Monash University (AU)
- Corresponding author
- Pedersen, B. K.
- Febbraio, M. A.
- Venue
- Diabetologia
- Published
- 2009-04-22
- Volume
- 52
- Issue
- 7
- Pages
- 1409-1418
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2083119172
- Semantic Scholar
- 4a8929d0be521f621ff5750ab854a4eab70f134f
- Cited by
- 722
- References
- 45
- Citations by year
- 2026: 33 · 2025: 56 · 2024: 57 · 2023: 48 · 2022: 67 · 2021: 54 · 2020: 54 · 2019: 54 · 2018: 44 · 2017: 45 · 2016: 29 · 2015: 45 · 2014: 29 · 2013: 38 · 2012: 22
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-02-19)
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Diabetes Australia Research Trust
- Diabetes Australia
- National Research Foundation
- Danmarks Grundforskningsfond (02-512-555, DG 02–512‐555, LSHM-CT-2004-005272, 504–14, LSHM-CT-2004-005272 EXGENESIS)
- Lundbeckfonden
- Novo Nordisk
- Novo Nordisk Fonden
- H. Lundbeck A/S
- Medical Research Council
- Australian Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- brain-derived neurotrophic factor, skeletal muscle, muscle contraction, fatty acid oxidation, AMPK, physical activity, TrkB, ERK, muscle lipid metabolism
- MeSH terms
- Acetyl-CoA Carboxylase, Animals, Cell Line, Exercise Test, Fats, Humans, Male, Mice, Inbred C57BL, Muscle Contraction, Oxidation-Reduction, Phosphorylation, Signal Transduction, Gene Expression, Muscle, Skeletal, Muscle Fibers, Skeletal, Brain-Derived Neurotrophic Factor, Receptor, trkB, Extracellular Signal-Regulated MAP Kinases, Lipid Metabolism, Mice, Rats, AMP-Activated Protein Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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