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Cited by 72Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismMuscle Physiology and Disorders

Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together?

Open access
Abou-Samra, Michel, Selvais, Camille M., Dubuisson, Nicolas, Brichard, Sonia M.·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21072620PMC PMC7178193
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Abstract

Adiponectin (ApN) is a hormone abundantly secreted by adipocytes and it is known to be tightly linked to the metabolic syndrome. It promotes insulin-sensitizing, fat-burning, and anti-atherosclerotic actions, thereby effectively counteracting several metabolic disorders, including type 2 diabetes, obesity, and cardiovascular diseases. ApN is also known today to possess powerful anti-inflammatory/oxidative and pro-myogenic effects on skeletal muscles exposed to acute or chronic inflammation and injury, mainly through AdipoR1 (ApN specific muscle receptor) and AMP-activated protein kinase (AMPK) pathway, but also via T-cadherin. In this review, we will report all the beneficial and protective properties that ApN can exert, specifically on the skeletal muscle as a target tissue. We will highlight its effects and mechanisms of action, first in healthy skeletal muscle including exercised muscle, and second in diseased muscle from a variety of pathological conditions. In the end, we will go over some of AdipoRs agonists that can be easily produced and administered, and which can greatly mimic ApN. These interesting and newly identified molecules could pave the way towards future therapeutic approaches to potentially prevent or combat not only skeletal muscle disorders but also a plethora of other diseases with sterile inflammation or metabolic dysfunction.

AI snapshot

Written from the paper’s full text.

TL;DR

Adiponectin (ApN) acts on skeletal muscle mainly through AdipoR1–AMPK signaling to improve insulin sensitivity, fatty-acid oxidation, inflammation/oxidative stress control, and regeneration. This review argues that ApN and its receptor agonists, especially AdipoRon, have therapeutic potential for dystrophic, sarcopenic, and metabolically diseased muscle.

Key findings

  • ApN circulates at ~μg/mL, at least 3 orders of magnitude higher than other hormones, as LMW trimer, MMW hexamer, and HMW 12–18 mers; HMW ApN elicits the most potent insulin-sensitizing effects.
  • In skeletal muscle, ApN activates AdipoR1–AMPK–PGC-1α/SIRT1, p38 MAPK/PPARα, and GLUT4 translocation, while repressing NF-κB and inflammasome pathways via PGC-1α, SIRT1, and miR-711.
  • Chronic exercise training increased circulating ApN and/or HMW ApN and muscle AdipoR1 in rodents (4–16 weeks) and humans (4–12 weeks), correlating with improved insulin sensitivity; ApN/AdipoR1 blockade diminished exercise benefits in aged SAMP10 mice.
  • In DMD models, ApN replenishment or oral AdipoRon for 2 months reduced inflammation/oxidative stress, improved myogenic factors and utrophin, and increased muscle force/endurance; ApN levels are decreased in mdx mice and human DMD patients.

Methods

  • Narrative review; no primary experiments reported.
  • Synthesizes in vivo rodent studies and in vitro human muscle cell studies, plus human exercise/observational data, across healthy muscle, exercise, diseased muscle (DMD, other dystrophies, sarcopenia), and ApN mimics.
  • Main analysis is qualitative synthesis of mechanisms and effects; no systematic search or meta-analysis is described.

Limitations

  • The paper states that interpreting exercise–ApN data is challenging because of differences in exercise type/program, participant characteristics and pathological context, inconsistent accounting for ApN oligomeric distribution, and difficulty attributing benefits to reduced fat mass versus exercise per se.
  • The paper states that ApN is not yet available for therapeutic use in humans; in vivo properties were studied only in rodents receiving/overexpressing the hormone or with ApN/AdipoR deficiency, although most mouse data were also confirmed in vitro in human muscle cells.
  • Evident from the text: as a narrative review, it does not report a systematic search, risk-of-bias assessment, or quantitative pooling, and conclusions rely on heterogeneous cited models and outcomes.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/ijms21072620

Cites

145 of 145 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 259 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    ApN/AdipoRon supplementation retained its anti-inflammatory properties in DMD human myotubes.

    “We found that ApN/AdipoRon supplementation retained its anti-inflammatory properties in DMD human myotubes [56,57,103]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [56] Lecompte, 2015, Involvement of adiponectin in the pathogenesis of dystrophinopathy, Skelet. Muscle source

      Not checked in the free run.

    • cites [57] Lecompte, 2017, Skeletal muscle secretome in Duchenne muscular dystrophy: A pivotal anti-inflammatory role of adiponectin, Cell. Mol. Life Sci. source

      Not checked in the free run.

    • cites [103] Abou-Samra, M., Selvais, C.M., Boursereau, R., Lecompte, S., Noel, L., and Brichard, S.M. (2020). AdipoRon, a new therapeutic prospect for Duchenne muscular dystrophy. J. Cachexia Sarcopenia Muscle. source

      Not checked in the free run.

  • Findingcitation

    Secretome analysis from myotubes revealed that ApN down-regulated the secretion of TNFα, IL-17A, sTNFRII, and CCL28.

    “secretome analysis from myotubes revealed that ApN down-regulated the secretion of two pro-inflammatory factors (TNFα and IL-17A), one soluble receptor (sTNFRII), and one chemokine (CCL28) [57].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [57] Lecompte, 2017, Skeletal muscle secretome in Duchenne muscular dystrophy: A pivotal anti-inflammatory role of adiponectin, Cell. Mol. Life Sci. source

      Not checked in the free run.

  • Findingcitation

    ApN/AdipoRon supplementation induced a shift in the secretion of downstream myokines toward a less inflammatory profile in DMD human myotubes.

    “and induced a shift in the secretion of downstream myokines toward a less inflammatory profile.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [56] Lecompte, 2015, Involvement of adiponectin in the pathogenesis of dystrophinopathy, Skelet. Muscle source

      Not checked in the free run.

    • cites [57] Lecompte, 2017, Skeletal muscle secretome in Duchenne muscular dystrophy: A pivotal anti-inflammatory role of adiponectin, Cell. Mol. Life Sci. source

      Not checked in the free run.

    • cites [103] Abou-Samra, M., Selvais, C.M., Boursereau, R., Lecompte, S., Noel, L., and Brichard, S.M. (2020). AdipoRon, a new therapeutic prospect for Duchenne muscular dystrophy. J. Cachexia Sarcopenia Muscle. source

      Not checked in the free run.

  • Findingcitation

    AdipoRon has beneficial and protective effects on dystrophic skeletal muscle in mdx mice and in human DMD myotubes.

    “Our latest study has brought to light the beneficial and protective effects of AdipoRon on the dystrophic skeletal muscle in mdx mice and in human DMD myotubes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [103] Abou-Samra, M., Selvais, C.M., Boursereau, R., Lecompte, S., Noel, L., and Brichard, S.M. (2020). AdipoRon, a new therapeutic prospect for Duchenne muscular dystrophy. J. Cachexia Sarcopenia Muscle. source

      Not checked in the free run.

  • Premisecitation

    ApN can counteract several facets of the metabolic syndrome through its insulin-sensitizing, fat-burning, and anti-inflammatory/oxidative properties.

    “Yet, ApN could thwart simultaneously several facets of this syndrome by its insulin-sensitizing, fat-burning, and anti-inflammatory/oxidative properties [1].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] Maury, 2010, Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome, Mol. Cell Endocrinol. source

      Not checked in the free run.

  • May combine two claims. 66
  • Classified as probably not a substantial claim. 5
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingcitation

    AdipoRon, mainly through AdipoR1-AMPK signaling, significantly mitigated skeletal muscle inflammation, oxidative stress, and damage, while markedly improving its regeneration and function.

    “Indeed, AdipoRon, mainly though AdipoR1-AMPK signaling, significantly mitigated skeletal muscle inflammation, oxidative stress, and damage, while markedly improving its regeneration and function [103].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [103] Abou-Samra, M., Selvais, C.M., Boursereau, R., Lecompte, S., Noel, L., and Brichard, S.M. (2020). AdipoRon, a new therapeutic prospect for Duchenne muscular dystrophy. J. Cachexia Sarcopenia Muscle. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AdipoR1 is a high-affinity receptor for gApN but can also bind full-length ApN; AdipoR2 shows intermediate affinity for both the globular and the full-length forms.

    “AdipoR1 is a high-affinity receptor for gApN but can also bind full-length ApN. AdipoR2 shows intermediate affinity for both the globular and the full-length forms [10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Yamauchi, 2003, Cloning of adiponectin receptors that mediate antidiabetic metabolic effects, Nature source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AdipoR1 is mainly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver.

    “AdipoR1 is mainly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver [10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Yamauchi, 2003, Cloning of adiponectin receptors that mediate antidiabetic metabolic effects, Nature source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AdipoR1 is tightly linked to activation of AMPK pathways, while AdipoR2 seems to be associated with activation of PPAR-α pathways.

    “AdipoR1 is tightly linked to activation of AMP-activated protein kinase (AMPK) pathways, while AdipoR2 seems to be associated with activation of peroxisome proliferator-activated receptor (PPAR)-α pathways [9,11].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [9] Yamauchi, 2007, Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions, Nat. Med. source

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    • cites [11] Iwabu, 2010, Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1, Nature source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ApN can be cleaved into a smaller globular fragment (gApN) by leukocyte elastases secreted from activated monocytes and neutrophils.

    “Finally, ApN could also be cleaved into a smaller globular fragment (gApN) by leukocyte elastases secreted from activated monocytes and neutrophils [7,8].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] Fruebis, 2001, Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice, Proc. Natl. Acad. Sci. USA. source

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    • cites [8] Waki, 2005, Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1, Endocrinology source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    T-cadherin is an additional binding partner for MMW and HMW isoforms of ApN.

    “T-cadherin is an additional binding partner for MMW and HMW isoforms of ApN [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Hug, 2004, T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin, Proc. Natl. Acad. Sci. USA source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ApN exerts anti-depressive effects by increasing hippocampal neurogenesis and reducing neuroinflammation.

    “It also exerts anti-depressive effects by increasing hippocampal neurogenesis and reducing neuroinflammation [29,30,31].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [29] Chabry, 2015, Enriched environment decreases microglia and brain macrophages inflammatory phenotypes through adiponectin-dependent mechanisms: Relevance to depressive-like behavior, Brainbehaviorand Immun. source

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    • cites [30] Yau, 2014, Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin, Proc. Natl. Acad. Sci. USA source

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    • cites [31] Zhang, 2016, Adiponectin Exerts Neurotrophic Effects on Dendritic Arborization, Spinogenesis, and Neurogenesis of the Dentate Gyrus of Male Mice, Endocrinology source

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    Premisecitation

    Skeletal muscle is an important target where ApN regulates energy metabolism, counterbalances inflammation and oxidative stress, and improves tissue regeneration.

    “Skeletal muscle is an important target where ApN regulates energy metabolism, counterbalances inflammation and oxidative stress, and improves tissue regeneration [5].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Kadowaki, 2006, Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome, J. Clin. Investig. source

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  • The quote only partly states this claim.

    Interpretationcitation

    Muscle ApN acts as a local protective mechanism to counteract excessive inflammatory reaction, ectopic fat deposit, and oxidative damage.

    “This paradigm was then validated in ApN-knockout (ApN-KO) mice submitted to inflammatory challenge: muscle electro-transfer of the ApN gene actually corrected local inflammation, oxidative stress and apoptosis [39,40].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] Jortay, 2012, Adiponectin and skeletal muscle: Pathophysiological implications in metabolic stress, Am. J. Pathol. source

      Not checked in the free run.

    • cites [40] Jortay, 2010, Local induction of adiponectin reduces lipopolysaccharide-triggered skeletal muscle damage, Endocrinology source

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  • May combine two claims.

    Premisecitation

    PGC-1α increases the activity of several transcription factors, thus stimulating expression of target genes leading to an increase of mitochondrial biogenesis and a shift towards an oxidative metabolism.

    “In turn, PGC-1α increases the activity of several transcriptions factors (TF), thus stimulating the expression of target genes leading to an increase of mitochondrial biogenesis and a shift towards an oxidative metabolism [11] (Figure 2).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Iwabu, 2010, Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1, Nature source

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  • May combine two claims.

    Interpretationreasoning

    ApN stimulates both expression and activation of PGC-1α.

    “Thus, ApN stimulates both expression and activation of PGC-1α.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    ApN may also induce Ca2+ influx, thereby activating CaMKKβ, which leads to increased expression of PGC-1α.

    “ApN may also induce Ca2+ influx, thereby activating CaMKKβ, which leads to increased expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a key player in mitochondrial function and biogenesis [42,43].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [42] Lin, 2005, Metabolic control through the PGC-1 family of transcription coactivators, Cell Metab. source

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    • cites [43] Kang, 2012, Role of PGC-1alpha signaling in skeletal muscle health and disease, Ann. New York Acad. Sci. source

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  • May combine two claims.

    Premisecitation

    ApN-transgenic mice are more sensitive to insulin, while ApN-KO mice are more resistant.

    “Similarly, ApN-transgenic (ApN-Tg) mice are more sensitive to insulin [21], while ApN-KO mice are more resistant [48].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [21] Bauche, 2007, Overexpression of adiponectin targeted to adipose tissue in transgenic mice: Impaired adipocyte differentiation, Endocrinology source

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    • cites [48] Maeda, 2002, Diet-induced insulin resistance in mice lacking adiponectin/ACRP30, Nat. Med. source

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  • May combine two claims.

    Premisecitation

    Administration of ApN lowered blood sugar and reduced insulin resistance in mice under a high-fat diet.

    “Administration of ApN lowered blood sugar and reduced insulin resistance in mice under a high-fat diet (HFD) [47].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Yamauchi, 2001, The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity, Nat. Med. source

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  • May combine two claims.

    Premisecitation

    As both oxidative stress and increased triglyceride content are linked to insulin resistance by inhibitory phosphorylation in IRS-1, ApN further acts as a sensitizing agent.

    “As both oxidative stress and increased triglyceride content are linked to insulin resistance by inhibitory phosphorylation in IRS-1, ApN further acts as a sensitizing agent [52,53].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [52] Houstis, 2006, Reactive oxygen species have a causal role in multiple forms of insulin resistance, Nature source

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    • cites [53] Tuncman, 2006, A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease, Proc. Natl. Acad. Sci. USA source

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  • May combine two claims.

    Premisecitation

    ApN activates AMPK signaling and P-AMPK inhibits p70S6K1, an enzyme that inactivates IRS-1 through phosphorylation on serine residues, thereby blocking the insulin signaling cascade.

    “First, ApN activates AMPK signaling and P-AMPK inhibits p70 ribosomal S6 kinase 1 (p70S6K1), an enzyme that inactivates the insulin receptor substrate-1 (IRS-1) through phosphorylation on serine residues, thereby blocking the insulin signaling cascade [50].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Wang, 2007, Adiponectin sensitizes insulin signaling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1, J. Biol. Chem. source

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  • May combine two claims.

    Premisecitation

    APPL1 promotes IRS-1 binding to the insulin receptor and enhances insulin signaling.

    “Eventually, APPL1 promotes IRS-1 binding to the insulin receptor and enhances insulin signaling [55].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [55] Ruan, 2016, Adiponectin signaling and function in insulin target tissues, J. Mol. Cell. Biol. source

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    Premisecitation

    M2 cells secrete the anti-inflammatory cytokine IL-10 and down-regulate the production of pro-inflammatory cytokines.

    “M2 cells are known to secrete the anti-inflammatory cytokine IL-10 and down-regulate the production of pro-inflammatory cytokines [58].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] Ohashi, 2010, Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype, J. Biol. Chem. source

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  • May combine two claims.

    Premisecitation

    Muscles of ApN-deficient mice displayed higher susceptibility to oxidative stress, inflammation, and apoptosis; all these abnormalities were exacerbated by acute (LPS) or chronic (obesogenic diet) inflammatory challenge and corrected by local electro-transfer of the ApN gene.

    “We previously showed that muscles of ApN-deficient mice displayed higher susceptibility to oxidative stress, inflammation, and apoptosis; all these abnormalities were exacerbated by acute (LPS) or chronic (obesogenic diet) inflammatory challenge and corrected by local electro-transfer of the ApN gene [39,40].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] Jortay, 2012, Adiponectin and skeletal muscle: Pathophysiological implications in metabolic stress, Am. J. Pathol. source

      Not checked in the free run.

    • cites [40] Jortay, 2010, Local induction of adiponectin reduces lipopolysaccharide-triggered skeletal muscle damage, Endocrinology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    After acute injury, skeletal muscle has a remarkable capacity to initiate a rapid and extensive regeneration, which is always associated with an inflammatory reaction.

    “After acute (reversible) injury, skeletal muscle has a remarkable capacity to initiate a rapid and extensive regeneration, which is always associated with an inflammatory reaction that varies in intensity [64].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Baghdadi, 2018, Regulation and phylogeny of skeletal muscle regeneration, Dev. Biol. source

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    Premisecitation

    Both PGC-1α and SIRT1 could repress NF-κB.

    “Indeed, both PGC-1α and SIRT1 could repress NF-κB [60,61] (Figure 2).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [60] Yang, 2010, Functional interplay between acetylation and methylation of the RelA subunit of NF-kappaB, Mol. Cell. Biol. source

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    • cites [61] Eisele, 2013, The peroxisome proliferator-activated receptor gamma coactivator 1alpha/beta (PGC-1) coactivators repress the transcriptional activity of NF-kappaB in skeletal muscle cells, J. Biol. Chem. source

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  • May combine two claims.

    Premisecitation

    ApN up-regulated the expression of miR-711, which, in turn, also repressed NF-κB as well as the inflammasome complex.

    “ApN up-regulated the expression of miR-711, which, in turn, also repressed NF-κB as well as the inflammasome complex [62,63].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [62] Boursereau, 2017, New targets to alleviate skeletal muscle inflammation: Role of microRNAs regulated by adiponectin, Sci. Rep. source

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    • cites [63] Boursereau, R., Abou-Samra, M., Lecompte, S., Noel, L., and Brichard, S.M. (2018). Downregulation of the NLRP3 inflammasome by adiponectin rescues Duchenne muscular dystrophy. BMC Biol., 16. source

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    Premisecitation

    Once activated, satellite cells will migrate, proliferate and give rise to myoblasts that differentiate into myotubes, which then fuse to restore damaged fibers or generate new one.

    “Once activated, satellite cells will migrate, proliferate and give rise to myoblasts that differentiate into myotubes, which then fuse to restore damaged fibers or generate new one [64] (Figure 3).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Baghdadi, 2018, Regulation and phylogeny of skeletal muscle regeneration, Dev. Biol. source

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    Premisecitation

    As gApN expression is low in the bloodstream, it is likely that most gApN is locally produced by muscle and acts in an autocrine or paracrine manner as a tissue regenerating hormone.

    “As gApN expression is low in the bloodstream, it is likely that most gApN is locally produced by muscle (satellite cells, differentiating myoblasts, ..) and acts in an autocrine or paracrine manner as a tissue regenerating hormone [66].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] Fiaschi, 2014, Adiponectin as a tissue regenerating hormone: More than a metabolic function, Cell. Mol. Life Sci. source

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    Premisecitation

    ApN overexpression in mice decreased necrotic region and increased regenerating myofibers after muscle injury; these effects were abolished in T-cadherin knockout mice.

    “It has recently been shown that ApN overexpression in mice decreased necrotic region and increased regenerating myofibers after muscle injury. Yet, these effects were abolished in T-cadherin knockout mice.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] Fiaschi, 2014, Adiponectin as a tissue regenerating hormone: More than a metabolic function, Cell. Mol. Life Sci. source

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    Premisecitation

    Both M1 macrophages and gApN play essential roles in the activation of satellite cells and the initiation of muscle regeneration.

    “Both M1 macrophages and gApN play essential roles in the activation of satellite cells and the initiation of muscle regeneration [65,66].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [65] Dufresne, 2016, Inflammation and muscle regeneration, a double-edged sword, Med. Sci.

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    • cites [66] Fiaschi, 2014, Adiponectin as a tissue regenerating hormone: More than a metabolic function, Cell. Mol. Life Sci. source

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  • May combine two claims.

    Premisecitation

    Regeneration of skeletal muscle depends on muscle stem cells, named satellite cells, which are kept in a quiescent state in a healthy muscle.

    “Regeneration of skeletal muscle also depends on muscle stem cells, named satellite cells, which are kept in a quiescent state in a healthy muscle [64].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Baghdadi, 2018, Regulation and phylogeny of skeletal muscle regeneration, Dev. Biol. source

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  • May combine two claims.

    Premisecitation

    ApN regulates several steps of the repair process by activating different signaling pathways, including p38MAPK and AMPK, and different myogenic TF such as Myf5, MyoD, Myogenin, and Mrf4.

    “Moreover, ApN appears to regulate several steps of the repair process by activating different signaling pathways, including p38MAPK and AMPK [66], and different myogenic TF such as Myf5, MyoD, Myogenin, and Mrf4 [56].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [66] Fiaschi, 2014, Adiponectin as a tissue regenerating hormone: More than a metabolic function, Cell. Mol. Life Sci. source

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    • cites [56] Lecompte, 2015, Involvement of adiponectin in the pathogenesis of dystrophinopathy, Skelet. Muscle source

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    Premisecitation

    gApN stimulates autophagy in myoblasts via an AMPK-dependent mechanism, promoting their survival and inhibiting their apoptosis.

    “gApN also stimulates autophagy in myoblasts via an AMPK-dependent mechanism, promoting their survival and inhibiting their apoptosis [71].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] Gamberi, 2016, Activation of autophagy by globular adiponectin is required for muscle differentiation, Biochim. Et Biophys. Acta source

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    Premisecitation

    ApN enhances PGC-1α expression and activity, which promotes oxidative metabolism to respond to the high energy demand for sustaining tissue-healing and regeneration.

    “Meanwhile, ApN enhances PGC-1α expression and activity, which promotes oxidative metabolism to respond to the high energy demand for sustaining tissue-healing and regeneration [74].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [74] Eming, 2017, Inflammation and metabolism in tissue repair and regeneration, Science source

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    Premisecitation

    Controlled accumulation of immune cells and increased energy metabolism are essential for appropriate muscle tissue remodeling.

    “Thus, controlled accumulation of immune cells and increased energy metabolism are essential for appropriate muscle tissue remodeling [65] (Figure 3).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [65] Dufresne, 2016, Inflammation and muscle regeneration, a double-edged sword, Med. Sci.

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    Premisecitation

    The rise in total plasma ApN was observed at moderate to high aerobic exercise intensity and was associated with a rise in HMW ApN, the metabolically active form of the hormone.

    “The rise in total plasma ApN was observed at moderate to high aerobic exercise intensity and was associated with a rise in HMW ApN, the metabolically active form of the hormone [79].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [79] Garekani, 2011, Exercise training intensity/volume affects plasma and tissue adiponectin concentrations in the male rat, Peptides source

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    Premisecitation

    Mice with muscle-specific disruption of AdipoR1 exhibited decreased PGC-1α expression and activity, decreased mitochondrial content and function, as well as decreased oxidative type 1 myofibers and oxidative-stress detoxifying enzymes. All these abnormalities were associated with decreased insulin sensitivity in muscle and reduced endurance capacity as assessed by treadmill running.

    “Likewise, mice with muscle-specific disruption of AdipoR1 exhibited decreased PGC-1α expression and activity, decreased mitochondrial content and function, as well as decreased oxidative type 1 myofibers and oxidative-stress detoxifying enzymes. All these abnormalities were associated with decreased insulin sensitivity in muscle and reduced endurance capacity as assessed by treadmill running [11].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Iwabu, 2010, Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1, Nature source

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    Premisecitation

    Usually, muscle ApN levels were unmodified, but this may depend on the studied muscle type.

    “Usually, muscle ApN levels were unmodified, but this may depend on the studied muscle type [89].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [89] Tam, 2020, Skeletal muscle adiponectin induction in obesity and exercise, Metabolism. source

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  • May combine two claims.

    Premisecitation

    Muscle may be a site of a severe form of chronic inflammation, which in turn plays a central role in the development or evolution of several myopathies.

    “Muscle may be a site of a severe form of chronic inflammation, which in turn plays a central role in the development or evolution of several myopathies [94,95].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [94] Acharyya, 2007, Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy, J. Clin. Investig. source

      Not checked in the free run.

    • cites [95] 2013, Cytokines and chemokines as regulators of skeletal muscle inflammation: Presenting the case of Duchenne muscular dystrophy, Mediat. Inflamm.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Running induces a rise in hippocampal ApN levels, while running-exerted hippocampal neurogenesis and antidepressant effects were diminished in ApN-KO mice.

    “Thus, running induces a rise in hippocampal ApN levels, while running-exerted hippocampal neurogenesis and antidepressant effects were diminished in ApN-KO mice [30].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Yau, 2014, Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Circulating levels of ApN are greatly decreased in mdx mice, an observation confirmed in human patients.

    “We and others have shown that circulating levels of ApN are greatly decreased in mdx mice (mouse model of DMD) [56,100], an observation confirmed in human patients [101].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [56] Lecompte, 2015, Involvement of adiponectin in the pathogenesis of dystrophinopathy, Skelet. Muscle source

      Not checked in the free run.

    • cites [100] Hathout, 2014, Discovery of serum protein biomarkers in the mdx mouse model and cross-species comparison to Duchenne muscular dystrophy patients, Hum. Mol. Genet. source

      Not checked in the free run.

    • cites [101] Hathout, 2019, Disease-specific and glucocorticoid-responsive serum biomarkers for Duchenne Muscular Dystrophy, Sci. Rep. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In humans, ApN up-regulation may be involved in the insulin-sensitizing effects of exercise and the protection against inflammation, muscle damage and excessive ROS production.

    “In humans, ApN up-regulation may be involved in the insulin-sensitizing effects of exercise and the protection against inflammation, muscle damage and excessive ROS production [90].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [90] Magherini, 2019, Oxidative stress in exercise training: The involvement of inflammation and peripheral signals, Free Radic. Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Trimeric and hexameric forms of ApN may pass the blood-brain barrier and ApN receptors are expressed in the brain.

    “This may be explained by the fact that trimeric and hexameric forms of ApN may pass the blood–brain barrier and that ApN receptors are expressed in the brain [92,93].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [92] Thundyil, 2012, Adiponectin receptor signalling in the brain, Br. J. Pharmacol. source

      Not checked in the free run.

    • cites [93] Kadowaki, 2008, The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS, FEBS Lett. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Although dystrophin gene mutations represent the primary cause of DMD, it is the secondary processes involving persistent inflammation and subsequent impaired regeneration that likely exacerbate disease progression.

    “Although dystrophin gene mutations represent the primary cause of DMD, it is the secondary processes involving persistent inflammation and subsequent impaired regeneration that likely exacerbate disease progression [94].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [94] Acharyya, 2007, Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy, J. Clin. Investig. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dystrophic muscles from mdx-ApN mice showed significant increased expression of the anti-inflammatory cytokine (IL-10), and were protected from T-lymphocytes and M1 (pro-inflammatory) macrophages infiltration.

    “Dystrophic muscles from mdx-ApN mice showed significant increased expression of the anti-inflammatory cytokine (IL-10), and were protected from T-lymphocytes and M1 (pro-inflammatory) macrophages infiltration [56].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [56] Lecompte, 2015, Involvement of adiponectin in the pathogenesis of dystrophinopathy, Skelet. Muscle source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ApN drastically reduced the expression of pro-inflammatory cytokines (TNF-α and IL-1β), and of oxidative-stress markers (peroxiredoxin, an antioxidant enzyme, and 4-hydroxynonenal, a lipid peroxidation product).

    “ApN drastically reduced the expression of pro-inflammatory cytokines (TNF-α and IL-1β), and of oxidative-stress markers (peroxiredoxin, an antioxidant enzyme, and 4-hydroxynonenal, a lipid peroxidation product).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [56] Lecompte, 2015, Involvement of adiponectin in the pathogenesis of dystrophinopathy, Skelet. Muscle source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    mdx-ApN mice displayed higher global muscular force and endurance.

    “Eventually, mdx-ApN mice displayed higher global muscular force and endurance”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [56] Lecompte, 2015, Involvement of adiponectin in the pathogenesis of dystrophinopathy, Skelet. Muscle source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    mdx-ApN-knockout mice exhibited lower global muscle force and endurance and increased muscle damage compared to regular mdx mice.

    “These mdx mice exhibited lower global muscle force and endurance as well as increased muscle damage when compared to regular mdx mice.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [102] Boursereau, 2017, Potential Therapeutic Action of Adiponectin in Duchenne Muscular Dystrophy, Am. J. Pathol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    mdx-ApN mice displayed higher global muscular force and endurance along with decreased muscle injury.

    “Eventually, mdx-ApN mice displayed higher global muscular force and endurance along with decreased muscle injury.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [56] Lecompte, 2015, Involvement of adiponectin in the pathogenesis of dystrophinopathy, Skelet. Muscle source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    ApN can act not only as a preventive, but also as a curative agent.

    “indicating that ApN can act not only as a preventive, but also as a curative agent [102].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [102] Boursereau, 2017, Potential Therapeutic Action of Adiponectin in Duchenne Muscular Dystrophy, Am. J. Pathol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Restoration of the myogenic program could result from attenuation of inflammation, insulin-sensitizing properties, or p38 MAPK activation.

    “Moreover, restoration of the myogenic program could result from attenuation of inflammation [56,103] as well as from insulin-sensitizing properties or p38 MAPK activation [68,69].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [56] Lecompte, 2015, Involvement of adiponectin in the pathogenesis of dystrophinopathy, Skelet. Muscle source

      Not checked in the free run.

    • cites [103] Abou-Samra, M., Selvais, C.M., Boursereau, R., Lecompte, S., Noel, L., and Brichard, S.M. (2020). AdipoRon, a new therapeutic prospect for Duchenne muscular dystrophy. J. Cachexia Sarcopenia Muscle. source

      Not checked in the free run.

    • cites [68] Fiaschi, T., Giannoni, E., Taddei, M.L., and Chiarugi, P. (2012). Globular adiponectin activates motility and regenerative traits of muscle satellite cells. PLoS ONE, 7. source

      Not checked in the free run.

    • cites [69] Fiaschi, 2009, Globular adiponectin induces differentiation and fusion of skeletal muscle cells, Cell Res. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    ApN/AdipoRon could counter some glucocorticoid side effects by enhancing insulin sensitivity, preventing obesity, hypertension and mood disturbances.

    “These medications could even counter some GC side effects by enhancing insulin sensitivity [105,106], preventing obesity [107], hypertension [108] and mood disturbances [107].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [105] Iwabu, 2015, Perspective of Small-Molecule AdipoR Agonist for Type 2 Diabetes and Short Life in Obesity, Diabetes Metab. J. source

      Not checked in the free run.

    • cites [106] Yamauchi, 2013, A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity, Nature source

      Not checked in the free run.

    • cites [107] Nicolas, 2018, Adiporon, an adiponectin receptor agonist acts as an antidepressant and metabolic regulator in a mouse model of depression, Transl. Psychiatry source

      Not checked in the free run.

    • cites [108] Hong, 2016, Adiponectin Receptor Agonist, AdipoRon, Causes Vasorelaxation Predominantly Via a Direct Smooth Muscle Action, Microcirculation source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Low concentration of serum ApN and selective reduction of its HMW oligomers were detected in patients with myotonic dystrophy type 1 (DM1).

    “Finally, low concentration of serum ApN together with a selective reduction of its HMW oligomers were detected in patients with myotonic dystrophy type 1 (DM1)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [111] Daniele, 2011, Decreased concentration of adiponectin together with a selective reduction of its high molecular weight oligomers is involved in metabolic complications of myotonic dystrophy type 1, Eur. J. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Col6a1−/− myoblasts displayed impaired glucose uptake and dysfunctioning mitochondria.

    “Col6a1−/− myoblasts also displayed several metabolic features, such as impaired glucose uptake and dysfunctioning mitochondria”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [96] Gamberi, T., Magherini, F., and Fiaschi, T. (2019). Adiponectin in Myopathies. Int. J. Mol. Sci., 20. source

      Not checked in the free run.

    • cites [110] Gamberi, 2019, Role of adiponectin in the metabolism of skeletal muscles in collagen VI-related myopathies, J. Mol. Med. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Sarcopenic obesity may be linked to low circulating ApN, which prevails in obese subjects and in those with metabolic syndrome.

    “Sarcopenic obesity may be linked to low circulating ApN, which prevails in obese subjects and in those with the metabolic syndrome.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    FoxO3 transcriptional activity is inhibited by PGC-1α and by the insulin/IGF1 signaling pathway, which also activates protein synthesis.

    “The transcriptional activity of FoxO3 is inhibited, on one hand, by PGC-1α and on the other hand, by the insulin/IGF1 signaling pathway, which also activates protein synthesis [75].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [75] Sandri, 2006, PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ApN or its mimic reversed sarcopenia in aged OVX rats by suppressing atrogenes and stimulating MyoD while enhancing PGC-1α expression.

    “Besides protection against osteopenia, ApN or its mimic reversed sarcopenia by suppressing atrogenes and stimulating MyoD while enhancing PGC-1α expression.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [118] China, 2017, Globular adiponectin reverses osteo-sarcopenia and altered body composition in ovariectomized rats, Bone source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ADP355 is a short peptide with sequence resembling the C-terminal globular domain of ApN and biological activity resembling gApN.

    “ADP355 is a short peptide with a sequence resembling the C-terminal globular domain of ApN and thus with a biological activity resembling gApN.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [121] Otvos, L., Haspinger, E., La Russa, F., Maspero, F., Graziano, P., Kovalszky, I., Lovas, S., Nama, K., Hoffmann, R., and Knappe, D. (2011). Design and development of a peptide-based adiponectin receptor agonist for cancer treatment. BMC Biotechnol., 11. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ApN corrected OVX-induced gain in body weight and changes in body composition (lean and fat mass), as well as insulin resistance.

    “ApN also corrected OVX-induced gain in body weight and changes in body composition (lean and fat mass), as well as insulin resistance [118].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [118] China, 2017, Globular adiponectin reverses osteo-sarcopenia and altered body composition in ovariectomized rats, Bone source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a mouse model of accelerated senescence, ApN mediates the stimulatory effects of exercise on muscle stem cell proliferation while mitigating apoptosis.

    “A study conducted in a mouse model of accelerated senescence reported that ApN mediates the stimulatory effects of exercise on muscle stem cell proliferation, while mitigating apoptosis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [80] Inoue, 2017, Exercise restores muscle stem cell mobilization, regenerative capacity and muscle metabolic alterations via adiponectin/AdipoR1 activation in SAMP10 mice, J. Cachexia Sarcopenia Muscle source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These changes were associated with improved exercise force and endurance in aged mice and resulted from activation of AdipoR1-AMPK axis.

    “These changes were associated with improved exercise force and endurance in these aged mice and resulted from activation of AdipoR1-AMPK axis [80].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [80] Inoue, 2017, Exercise restores muscle stem cell mobilization, regenerative capacity and muscle metabolic alterations via adiponectin/AdipoR1 activation in SAMP10 mice, J. Cachexia Sarcopenia Muscle source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In some life-threatening conditions associated with sarcopenia (chronic heart failure or kidney disease), ApN levels may be paradoxically elevated and could represent unsuccessful compensatory mechanisms against inflammation and oxidative stress.

    “However, in some life-threatening conditions associated with sarcopenia (chronic cardiac heart failure or kidney disease), ApN levels may be paradoxically elevated in patients and could represent unsuccessful compensatory mechanisms against inflammation and oxidative stress [116].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Arai, Y., Kamide, K., and Hirose, N. (2019). Adipokines and Aging: Findings from Centenarians and the Very Old. Front. Endocrinol, 10. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ADP355 restricted proliferation of cancer lines in vitro and suppressed growth of human breast cancer xenografts in mice in vivo.

    “ADP355 was shown to restrict the proliferation of cancer lines in vitro and suppress the growth of human breast cancer xenografts in mice in vivo [121].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [121] Otvos, L., Haspinger, E., La Russa, F., Maspero, F., Graziano, P., Kovalszky, I., Lovas, S., Nama, K., Hoffmann, R., and Knappe, D. (2011). Design and development of a peptide-based adiponectin receptor agonist for cancer treatment. BMC Biotechnol., 11. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ADP-1 increased glucose uptake in rat skeletal muscle cell lines and improved glucose tolerance in db/db mice.

    “It was shown to increase glucose uptake in rat skeletal muscle cells lines and improved glucose tolerance in db/db mice [123].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [123] Sayeed, 2018, A collagen domain-derived short adiponectin peptide activates APPL1 and AMPK signaling pathways and improves glucose and fatty acid metabolisms, J. Biol. Chem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Osmotin is a plant protein with structural and functional similarities to ApN, and AdipoR1 is the mammalian homologue of the osmotin receptor.

    “Osmotin is a plant protein possessing structural and functional similarities to ApN, and with AdipoR1 being the mammalian homologue of the osmotin receptor [124].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [124] Anil Kumar, S., Hima Kumari, P., Shravan Kumar, G., Mohanalatha, C., and Kavi Kishor, P.B. (2015). Osmotin: A plant sentinel and a possible agonist of mammalian adiponectin. Front. Plant Sci., 6. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ADP-1 is a highly conserved 13-residue segment peptide from ApN's collagen domain, with similar positive effects on glucose and fatty-acid metabolism.

    “ADP-1 is a highly conserved 13-residue segment peptide from ApN’s collagen domain, with similar positive effects on glucose and fatty-acid metabolism.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [123] Sayeed, 2018, A collagen domain-derived short adiponectin peptide activates APPL1 and AMPK signaling pathways and improves glucose and fatty acid metabolisms, J. Biol. Chem. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Additional AdipoR activating peptides have been identified in silico.

    “Additional AdipoR activating peptides have also been identified in silico [120].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [120] Liu, 2019, Examining the Potential of Developing and Implementing Use of Adiponectin-Targeted Therapeutics for Metabolic and Cardiovascular Diseases, Front. Endocrinol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    PEGylated BHD1028 is an AdipoR1 agonist and was proposed for treatment of diabetes.

    “PEGylated BHD1028 is an AdipoR1 agonist and was proposed for the treatment of diabetes [134].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [134] Kim, S., Lee, Y., Kim, J.W., Son, Y.J., Ma, M.J., Um, J.H., Kim, N.D., Min, S.H., Kim, D.I., and Kim, B.B. (2018). Discovery of a novel potent peptide agonist to adiponectin receptor 1. PLoS ONE, 13. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tiliroside is a plant derived glycosidic flavonoid with ApN-like effect.

    “Tiliroside is a plant derived glycosidic flavonoid with ApN-like effect.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [136] Goto, 2012, Tiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic mice, J. Nutr. Biochem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tiliroside stimulated fatty-acid oxidation in liver and skeletal muscle in obese-diabetic mice and attenuated obesity-induced metabolic disorders.

    “It was shown to stimulate fatty-acid oxidation in liver and skeletal muscle in obese-diabetic mice, and attenuate obesity-induced metabolic disorders [136].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [136] Goto, 2012, Tiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic mice, J. Nutr. Biochem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AdipoRon is an orally active synthetic small-molecule AdipoRs agonist identified in 2013 by Okada-Iwabu et al. after screening a compound library to identify those that bind to AdipoRs and greatly activate AMPK.

    “Last but not least, the most compelling mimic to date is AdipoRon, an orally active synthetic small-molecule AdipoRs agonist identified in 2013 by Okada-Iwabu et al. after screening a compound library to identify those that bind to AdipoRs and greatly activate AMPK [106].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [106] Yamauchi, 2013, A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity, Nature source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Pep70 is a potential AdipoR1 agonist and could inhibit cell proliferation and suppress expression of collagen type I alpha1 and TGF-β1, protecting against fibrotic responses.

    “Pep70 is a potential AdipoR1 agonist and could significantly inhibit the proliferation of cells and suppress the expression of collagen type I alpha1 and TGF-β1, thus protecting against fibrotic responses [133].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [133] Ma, 2017, A potent peptide as adiponectin receptor 1 agonist to against fibrosis, J. Enzym. Inhib. Med. Chem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GTDF is a flavonoid-type compound, a naturally occurring quercetin analogue.

    “GTDF is a flavonoid-type compound, a naturally occurring quercetin analogue”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [135] Singh, 2014, Orally active osteoanabolic agent GTDF binds to adiponectin receptors, with a preference for AdipoR1, induces adiponectin-associated signaling, and improves metabolic health in a rodent model of diabetes, Diabetes source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    ApN protects muscle against metabolic disturbances, inflammation, and oxidative stress, and favors regeneration, even when abnormalities are extremely severe such as in dystrophinopathies.

    “It protects muscle against metabolic disturbances, inflammation, and oxidative stress, and favors regeneration, even when abnormalities are extremely severe such as in dystrophinopathies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    ApN is a powerful hormone that exerts various beneficial effects on different organs and shares similar signaling pathways to exercise.

    “ApN is a powerful hormone that exerts various beneficial effects on different organs and shares similar signaling pathways to exercise.”
    Quote in the paperSubstantial claim
71 of 71

  • The paper relies on this without support.

    ApN is not yet available for therapeutic use in humans.

    “As ApN is not yet available for therapeutic use in humans, its properties discussed hereafter have been studied in vivo only in rodents receiving/overexpressing the hormone or conversely exhibiting ApN/AdipoR deficiency.”

  • The paper relies on this without support.

    Exercise training improves insulin sensitivity and lipid profile, and potentially reduces fat mass.

    “Exercise training is well-known to improve insulin sensitivity and lipid profile, and to potentially reduce fat mass.”

  • The paper relies on this without support.

    Glucocorticoids are the only medication commonly used to manage DMD.

    “To date, glucocorticoids (GCs) are the only medication commonly used to manage DMD.”

  • The paper relies on this without support.

    ApN possesses complex three-dimensional structures, circulates at high concentration in plasma, and must be injected.

    “ApN possesses complex three-dimensional structures, it circulates at high concentration in plasma and, as with any other peptide, it must be injected.”

  • The paper relies on this without support.

    Glucocorticoids promote protein catabolism and induce muscle loss.

    “Glucocorticoids are known to promote protein catabolism and induce muscle loss.”

  • The paper relies on this without support.

    NLRP3 promotes the cleavage of pro-IL-1β and pro-IL-18 leading to their active forms.

    “NLRP3 promotes the cleavage of pro-IL-1β and pro-IL-18 leading to their active forms.”

  • The paper relies on this without support.

    Antioxidant detoxifying enzymes may reduce oxidative stress.

    “First, antioxidant detoxifying enzymes may reduce the oxidative stress.”
7 of 7

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?

  • Exercise-induced adiponectin reduces white fat synthesis to mitigate muscle atrophy, with mechanisms including enhanced insulin sensitivity, improved glucose uptake, promotion of myogenesis, inhibition of muscle protein degradation, and increased muscle hypertrophy.

    “Exercise-induced adiponectin also reduces white fat synthesis to mitigate muscle atrophy, with the primary mechanisms underlying this effect including enhanced insulin sensitivity, improved glucose uptake, promotion of myogenesis, inhibition of muscle protein degradation, and increased muscle hypertrophy [87,88].”

    From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [87]

  • AdipoR1-deficient mice show reduced PGC-1α expression, mitochondrial biogenesis and function, and endurance training capacity.

    “AdipoR1-deficient mice show reduced PGC-1α expression, mitochondrial biogenesis and function, and endurance training capacity [87].”

    From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [87]

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.

  • Adiponectin mimic named GTFD in one section and GTDF in another

    Minor

    The sarcopenia section identifies the mimic as GTFD and directs readers to Section 6.2, which names it GTDF. The compound identifier is inconsistent.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Dufresne, 2016, Inflammation and muscle regeneration, a double-edged sword, Med. Sci., 32, 591

Cited by

Sorted by citations

Related

Authors
Abou-Samra, M., Selvais, C. M., Dubuisson, N., & Brichard, S. M.
Affiliations
  • Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector, Université Catholique de Louvain, 1200 Brussels, Belgium
  • UCLouvain (BE)
Corresponding author
Brichard, Sonia M.
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-04-09
Volume
21
Issue
7
Pages
2620
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms21072620
PMC
PMC7178193
OpenAlex
W3015379732
Semantic Scholar
c5a928a74e602a47d2c6b8bacf880ddf63b556a0
Cited by
72
References
145
Citations by year
2026: 11 · 2025: 9 · 2024: 8 · 2023: 15 · 2022: 11 · 2021: 14 · 2020: 2 · 2019: 1 · 2018: 1
FWCI
1.53
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Association Belge contre les Maladies Neuro-Musculaires (N/A)
  • AFM-Téléthon (H121203009)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
adiponectin, skeletal muscle, AdipoR1, AMPK, T-cadherin, insulin sensitivity, fat oxidation, metabolic syndrome, type 2 diabetes, obesity, cardiovascular disease, muscle inflammation, muscle damage, myogenesis, exercise mimetics, oxidative stress, anti-inflammatory activity
MeSH terms
Animals, Disease Susceptibility, Humans, Inflammation, Insulin, Mitochondria, Obesity, Signal Transduction, Exercise, Oxidative Stress, Muscle, Skeletal, Molecular Mimicry, Metabolic Syndrome, Adiponectin, Biosynthetic Pathways, 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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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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