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Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons
Open accessAbstract
Summary Leptin plays a pivotal role in regulation of energy balance. Via unknown central pathways leptin also affects peripheral glucose homeostasis and locomotor activity. We hypothesized that specifically Pro-opiomelanocortin (POMC) neurons mediate those actions. To examine this possibility we applied Cre-Lox technology to express leptin receptors (ObRb) exclusively in POMC neurons of the morbidly obese, profoundly diabetic, and severely hypoactive leptin receptor deficient Leprdb/db mice. We here show that expression of ObRb only in POMC neurons leads to a marked decrease in energy intake and a modest reduction in body weight in Leprdb/db mice. Remarkably, blood glucose levels are entirely normalized. This normalization occurs independently of changes in food intake and body weight. In addition, physical activity is greatly increased despite profound obesity. Our results suggest that leptin signaling exclusively in POMC neurons is sufficient to stimulate locomotion and prevent diabetes in the severely hypoactive and hyperglycemic obese Leprdb/db mice.
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TL;DR
Expressing leptin receptors (HA-ObRb) exclusively in POMC neurons of leptin-receptor-deficient Leprdb/db mice normalized blood glucose and roughly doubled locomotor activity, despite persistent severe obesity. These effects occurred largely independently of reduced food intake and body weight.
Key findings
- Blood glucose was fully normalized in 5-week-old HA-ObRb/Pomc-Cre/Leprdb/db mice; pair-feeding Leprdb/db mice a ~30% reduced intake for 3 weeks did not reduce hyperglycemia, indicating glucose correction was independent of energy intake and body weight.
- Food intake fell 30–40% and body weight decreased 10–15% versus Leprdb/db mice, but body weight remained 65–90% above wild-type mice; whole-body energy expenditure did not differ.
- Locomotor activity increased ~100% versus Leprdb/db mice and was not statistically different from lean wild-type mice.
- Serum insulin was reduced by 60%, insulin tolerance improved (p=0.021 vs Leprdb/db), total endocrine islet mass increased 2.5-fold, and hypothalamic α-MSH peptide levels increased 3.5-fold versus Leprdb/db mice.
Methods
- Cre-Lox transgenic strategy: HA-tagged ObRb was expressed in POMC neurons by mating HA-ObRb transgenic mice with Pomc-Cre mice, then crossed onto Leprdb/db background to generate HA-ObRb/Pomc-Cre/Leprdb/db mice.
- Phenotyping included immunohistochemistry for HA, β-endorphin, P-STAT3, and α-MSH; leptin-induced STAT3 phosphorylation counts; blood glucose, insulin, leptin, triglycerides; insulin and glucose tolerance tests; pancreas histology; CLAMS indirect calorimetry and locomotor activity; hypothalamic neuropeptide mRNA by real-time PCR and peptide enzyme immunoassays.
- Data are means ± SEM; significance set at p ≤ 0.05; Student’s t-tests, and for insulin tolerance tests general linear models with one-way ANOVA and protected least significant-differences.
Limitations
- The paper states the specific mechanism by which POMC leptin signaling normalizes blood glucose is unknown and likely involves neuroendocrine and/or autonomic actions; the relative contributions of the melanocortin system, pancreas, muscle, and liver remain to be determined.
- The paper states that a possible role of NTS POMC neurons cannot be excluded, although the authors conclude arcuate POMC neurons are responsible; it also notes only ~50% of hypothalamic POMC neurons expressed functional HA-leptin receptors, with the reason unclear.
- The paper states that whether increased islet mass is a direct result of leptin action via POMC neurons or an indirect consequence of altered metabolic state/incretin action remains to be elucidated, and the extent to which increased locomotion contributes to lowered glucose remains to be determined.
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Claims the paper makes
48 Own result · 42 Not checked yet · 23 Own interpretation · 3 Own method · 2 No basis given · 1 Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Moreover, deletion of leptin-receptors from AgRP neurons results in a modest reduction in activity (van de Wall et al., 2007)”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
What the sources say
- Supportedcites van de Wall et al., 2007 source
Figure 4C, reproduced in the section on selective LEPR ablation (page unavailable), reports significantly reduced locomotor activity in male mice lacking leptin receptors in AgRP neurons during the dark phase. The discussion also describes these mice as having reduced locomotor activity; it does not quantify the reduction as “modest.” (LLM, conf=0.88)
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- Supported
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 here show that expression of ObRb only in POMC neurons leads to a marked decrease in energy intake and a modest reduction in body weight in Leprdb/db mice.”
- Also stated in: § Leptin signaling in POMC neurons of Leprdb/db mice reduces body weight and food intake · plain
“Food intake was markedly reduced (30–40%) in HA-ObRb/Pomc-Cre/Leprdb/db mice compared to Leprdb/db control mice, but remained significantly higher than wild type mice (Figure 3C and 3D).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Abstract
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- Also stated in: § Leptin signaling in POMC neurons of Leprdb/db mice reduces body weight and food intake · plain
None of the sources cited for this claim have been checked yet.
In the paper
“HA-ObRb/Pomc-Cre/Leprdb/db mice had modestly increased hypothalamic POMC mRNA (Figure 6A) consistent with a role of leptin signaling to stimulate Pomc gene expression (Munzberg et al., 2003; Thornton et al., 1997).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Effects of leptin signaling in POMC neurons on neuropeptides
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Importantly, P-STAT3 was not detected in the ventromedial (VMH), the dorsomedial (DMH), and the premammillary (PMV) nuclei of HA-ObRb/Pomc-Cre/Leprdb/db mice, regions known to express P-STAT3 in leptin-treated wild type mice (Figure 2C)(Munzberg et al., 2004).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Generation of mice expressing leptin receptors in POMC neurons
What the sources say
- Not checked yetcites Munzberg et al., 2004 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, HA-ObRb/Pomc-Cre mice on a pure FVB background were indistinguishable from wild type littermates with regard to body weight, food intake, circulating glucose and insulin, and glucose- and insulin-tolerance (Supplemental Figures 4 and 5).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Normalization of glucose by ObRb in POMC neurons in Leprdb/db mice
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“As shown in Figure 4E, this food restriction did not reduce hyperglycemia in Leprdb/db mice.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Normalization of glucose by ObRb in POMC neurons in Leprdb/db mice
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Islets from HA- ObRb/Pomc-Cre/Leprdb/db mice appeared structurally intact.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Leptin receptors in POMC neurons of Leprdb/db mice increases islet mass
hedged- Asserted: passes — The authors put it forward as true.
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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
“In 12 weeks old fasted HA-ObRb/pomc-Cre/Leprdb/db mice, blood glucose levels were markedly reduced as compared to Leprdb/db mice (Supplemental Figure 2A), despite only a slight decrease in weight (Supplemental Figure 2B).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Normalization of glucose by ObRb in POMC neurons in Leprdb/db mice
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Fat mass and circulating leptin levels tended towards a modest decrease in HA-ObRb/Pomc-Cre/Leprdb/db mice versus Leprdb/db mice (Figure 3E and 3F, Table 1).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Leptin signaling in POMC neurons of Leprdb/db mice reduces body weight and food intake
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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 found a 50% decreased level of P-STAT3 in HA-ObRb/Pomc-Cre/Leprdb/db mice relative to control mice (Supplemental Figure 1).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Generation of mice expressing leptin receptors in POMC neurons
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 35
- Probably not a substantial claim. 16
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
“Moreover, total hypothalamic α-MSH peptide levels were 3.5 fold increased in HA-ObRb/Pomc-Cre/Leprdb/db mice relative to Leprdb/db mice, and were similar to wild type levels (Figure 6D).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Effects of leptin signaling in POMC neurons on neuropeptides
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“As predicted, leptin did not induce P-STAT3 in the hypothalamus of HA-ObRb/Leprdb/db control mice (Figure 2A) or Pomc-Cre/Leprdb/db control mice (not shown).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Generation of mice expressing leptin receptors in POMC neurons
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Body weights of HA-ObRb/Pomc-Cre/Leprdb/db mice were slightly decreased (10–15%) as compared to Leprdb/db mice, but remained greatly increased (65–90%) relative to wild type mice (Figure 3A and 3B).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Leptin signaling in POMC neurons of Leprdb/db mice reduces body weight and food intake
plain- Asserted: passes — The authors put it forward as true.
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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
“Insulin tolerance was significantly improved in HA-ObRb/pomc-Cre/Leprdb/db mice relative to Leprdb/db mice over time (p=0.021), and trended towards a decrease (0–30 min) compared to wild type mice (p=0.097)(Figure 4H).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Normalization of glucose by ObRb in POMC neurons in Leprdb/db mice
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The activity of HA-ObRb/Pomc-Cre/Leprdb/db mice was not statistically different from lean wild type mice, although there was a trend towards a reduction.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Leptin receptors in POMC neurons increases activity
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“As expected, HA immunoreactive (IR) cells were found in the ARC of HA-ObRb/Pomc-Cre mice (Figure 1B), but not in brains from HA-ObRb control mice (Figure 1B).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Generation of mice expressing leptin receptors in POMC neurons
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Body length (Table 1) and lean mass was not different among these groups (not shown).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Leptin signaling in POMC neurons of Leprdb/db mice reduces body weight and food intake
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
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
“Food intake was markedly reduced (30–40%) in HA-ObRb/Pomc-Cre/Leprdb/db mice compared to Leprdb/db control mice, but remained significantly higher than wild type mice (Figure 3C and 3D).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Leptin signaling in POMC neurons of Leprdb/db mice reduces body weight and food intake
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Serum insulin levels were reduced by 60% in HA-ObRb/Pomc-Cre/Leprdb/db mice compared to Leprdb/db control mice, but elevated relative to control animals (Figure 4G).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Normalization of glucose by ObRb in POMC neurons in Leprdb/db mice
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The HA-tag did not interfere with STAT3 activation by ObRb in transfected cells (not shown).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Generation of mice expressing leptin receptors in POMC neurons
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds.
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
“Total endocrine mass was increased by 2.5 fold in HA-ObRb/Pomc-Cre/Leprdb/db mice as compared to both Leprdb/db and wild type mice, and was caused by increased islet size.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Leptin receptors in POMC neurons of Leprdb/db mice increases islet mass
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Further, 60% (+/−5%) of POMC neurons in leptin-treated wild type mice and less than 2% of POMC neurons in Leprdb/db mice expressed P-STAT3.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Generation of mice expressing leptin receptors in POMC neurons
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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
“Counts of β-Endorphin and P-STAT3 positive neurons (Figure 2D) in leptin-treated HA- ObRb/Pomc-Cre/Leprdb/db mice showed that 56% (+/−24%) of POMC neurons expressed P-STAT3, and that 88% (+/−8%) of the P-STAT3 IR cells were POMC neurons.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Generation of mice expressing leptin receptors in POMC neurons
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“Despite lack of detectable HA positive neurons in this region (not shown), P-STAT3 IR cells were detected in the NTS of HA-ObRb/Pomc-Cre/Leprdb/db mice (not shown).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Generation of mice expressing leptin receptors in POMC neurons
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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 found a marked 30–40% reduction in energy intake in mice expressing leptin receptors solely in POMC neurons relative to Leprdb/db mice, but did not detect changes in whole body O2 consumption.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
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In the paper
“In addition, ventricular infusion of α-MSH into rats enhances acute insulin-stimulated peripheral glucose uptake and reduces hepatic glucose production, while a melanocortin receptor antagonist exerts opposite effects (Obici et al., 2001).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Introduction
What the sources say
- Not checked yetcites Obici et al., 2001 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Mice lacking leptin receptors only in POMC or AgRP neurons are mildly obese, demonstrating that both groups of cells are partly required for maintenance of body weight homeostasis by leptin (Balthasar et al., 2004; van de Wall et al., 2007).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Introduction
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The absence of leptin or leptin receptors in Lepob/ob mice or Leprdb/db mice respectively, results in morbid obesity, hyperphagia, severe hyperglycemia and insulin resistance, and marked hypoactivity (Chen et al., 1996; Coleman, 1978; Lee et al., 1996; Pelleymounter et al., 1995; Tartaglia et al., 1995; Zhang et al., 1994).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Insulin resistance is present before the onset of obesity in melanocortin-4-receptor deficient mice (Fan et al., 2000).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Introduction
What the sources say
- Not checked yetcites Fan et al., 2000 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, leptin dramatically improves insulin sensitivity in human lipodystrophy and in lipodystrophic mouse models which are characterized by low serum leptin levels and by severe insulin resistance (Oral et al., 2002; Petersen et al., 2002; Shimomura et al., 1999).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Introduction
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“POMC neurons are depolarized by leptin, leading to release of α-melanocyte stimulating hormone (α-MSH), a POMC-derived neuropeptide that mediates its anorexigenic effects through activation of melanocortin receptors (Cone, 2005; Cowley et al., 2001; Schwartz et al., 2000).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In addition, intracerebroventricular leptin can acutely stimulate glucose uptake in skeletal muscle (Cusin et al., 1998; Haque et al., 1999; Kamohara et al., 1997; Minokoshi et al., 1999)”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“and inhibit hepatic glucose production (Pocai et al., 2005; van den Hoek et al., 2008).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“AgRP is an endogenous melanocortin receptor antagonist that potently stimulates feeding (Ollmann et al., 1997).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Introduction
What the sources say
- Not checked yetcites Ollmann et al., 1997 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Long-term impairment of central melanocortin receptor action in mice results in marked obesity, hyperinsulinemia, and late-onset hyperglycemia (Huszar et al., 1997).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Introduction
What the sources say
- Not checked yetcites Huszar et al., 1997 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Restoration of leptin-receptors in arcuate neurons greatly increases voluntary locomotor activity in Leprdb/db mice (Coppari et al., 2005), but the specific neurons mediating this action remain unknown.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Leptin receptors in POMC neurons increases activity
What the sources say
- Not checked yetcites Coppari et al., 2005 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
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 contrast, our studies demonstrate that leptin receptor signaling in POMC neurons is sufficient to exert remarkable control of serum glucose concentrations and locomotion.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
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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
“The total islet mass did not correlate with circulating insulin levels between Leprdb/db and HA-ObRb/Pomc-Cre/Leprdb/db groups, indicating differential β-cell regulation and/or functionality.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Leptin receptors in POMC neurons of Leprdb/db mice increases islet mass
hedged- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Consistent with this, central leptin administration can acutely increase muscle glucose uptake (Kamohara et al., 1997) and decrease hepatic glucose production (van den Hoek et al., 2008) through altered autonomic output (Haque et al., 1999).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, deletion of ObRb from only POMC neurons of lean mice does not lead to hyperglycemia (Balthasar et al., 2004) or hypoactivity (Shi et al., 2008), suggesting that leptin receptors in POMC neurons are not required for normal regulation of glucose balance and locomotion.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
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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
“Our data suggest that the normalization is a direct consequence of leptin action in POMC neurons and is not secondary to differences in energy consumption or body weight.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
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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
“altogether demonstrating that the pair-feeding paradigm greatly impacted the metabolic status of Leprdb/db mice and that this alone was insufficient to attenuate hyperglycemia.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Results > Normalization of glucose by ObRb in POMC neurons in Leprdb/db mice
boosteddirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, the central melanocortin pathway can increase sympathetic drive to peripheral tissues and enhance insulin-dependent glucose disposal (Brito et al., 2007; Heijboer et al., 2005; Rahmouni et al., 2003).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Our results suggest that leptin signaling exclusively in POMC neurons is sufficient to stimulate locomotion and prevent diabetes in the severely hypoactive and hyperglycemic obese Leprdb/db mice.”
- Also stated in: § Discussion · plain
“We show here that expression of ObRb only in POMC neurons is sufficient to correct diabetes and drastically stimulate locomotor activity of the leptin receptor-deficient Leprdb/db mice.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · plain
In the paper
“This suggests that POMC neurons play a partial role in attenuating food intake by leptin, but have little if any role in leptin’s action to increase energy expenditure (Hwa et al., 1997).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
What the sources say
- Not checked yetcites Hwa et al., 1997
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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
“we conclude that arcuate POMC neurons, but not NTS POMC neurons, are responsible for mediating those effects of leptin.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
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 phenotype of HA-ObRb/Pomc-Cre/Leprdb/db mice is directly comparable to the phenotype resulting from arcuate-specific restoration of leptin receptors in Coppari et al. (2005).
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
“The housekeeping gene cyclophilin was used for normalization.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Experimental Procedures > Hypothalamic Neuropeptide mRNA
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“A role of skeletal muscle AMP-activated protein kinase (AMPK) in mediating exercise-dependent stimulation of insulin sensitivity and glucose uptake has been reported (Musi and Goodyear, 2003).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
What the sources say
- Not checked yetcites Musi and Goodyear, 2003
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
“our data show that leptin signaling specifically in hypothalamic POMC neurons is sufficient to correct diabetes and greatly increase locomotion in Leprdb/db mice”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Exercise training increases insulin-sensitivity and improves glucose homeostasis (Hespel et al., 1996; Ryder et al., 2001).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. It may state two separate claims as one.
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
“Animal care and procedures were approved by the Institutional Animal Care and Use Committee at Beth Israel Deaconess Medical Center.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Experimental Procedures > Animal Care
plain- Asserted: passes — The authors put it forward as true.
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- 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
“These data combined therefore suggest that leptin signaling in ~50% of hypothalamic POMC neurons are sufficient to normalize blood glucose levels and stimulate physical activity.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > 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: The phenotype resulting from unilateral restoration of endogenous leptin receptors in arcuate neurons is strikingly similar to that of HA-ObRb/Pomc-Cre/Leprdb/db mice.
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
“a possible role of these cells in mediating some of the phenotypic changes in HA-ObRb/Pomc-Cre/Leprdb/db animals cannot be excluded.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
hedgedconditional- 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.
In the paper
“In further support of this, deletion of ObRb in the ventromedial hypothalamus (VMH) in 12 wks old mice increases body weight by ~10% and a combined loss in POMC and VMH neurons increases weight by 25%, suggesting additive effects (Dhillon et al., 2006).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
What the sources say
- Not checked yetcites Dhillon et al., 2006 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In addition, central administration of melanocortin receptor agonists is sufficient to activate muscle AMPK phosphorylation in mice (Tanaka et al., 2007).”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Discussion
What the sources say
- Not checked yetcites Tanaka et al., 2007 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.
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
“Only littermates with the same mixed genetic background (FVB/C57BLKSJ) were compared, except for Supplemental Figures 4 and 5 where pure FVB non-Leprdb/db mice were studied.”
§ Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons > Experimental Procedures > Generation of HA-ObRb/Pomc-Cre/Leprdb/db Mice
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.
The paper relies on this without support.
The specific arcuate neurons responsible for mediating leptin's effects on glucose balance and voluntary locomotor activity are unspecified.
“Genetic studies in mice suggest that the arcuate hypothalamic nucleus plays a major role in mediating effects of leptin on glucose balance and on voluntary locomotor activity (Coppari et al., 2005), however the specific arcuate neurons responsible remain unspecified.”
The paper relies on this without support.
The extent to which POMC neuronal action can prevent severe hyperglycemia is unknown.
“However the extent to which POMC neuronal action can prevent severe hyperglycemia is unknown.”
The paper relies on this without support.
The pair-feeding paradigm and weight-matching adequately isolate the effects of leptin signaling in POMC neurons from changes in energy intake and body weight.
“To examine whether this reduction in circulating glucose in HA-ObRb/Pomc-Cre/Leprdb/db mice was dependent of energy intake, eight weeks old female Leprdb/db mice were pair-fed (~30% intake reduction) to ad libitum fed HA-ObRb/Pomc-Cre/Leprdb/db littermates for three weeks (Figure 4F).”
The paper relies on this without support.
The phenotype of HA-ObRb/Pomc-Cre/Leprdb/db mice is directly comparable to the phenotype resulting from arcuate-specific restoration of leptin receptors in Coppari et al. (2005).
“Since these findings are directly comparable to the phenotype of our HA-ObRb/Pomc-Cre/Leprdb/db mice we conclude”
The paper relies on this without support.
The phenotype resulting from unilateral restoration of endogenous leptin receptors in arcuate neurons is strikingly similar to that of HA-ObRb/Pomc-Cre/Leprdb/db mice.
“results in a phenotype strikingly similar to that of our HA-ObRb/Pomc-Cre/Leprdb/db mice”
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
“These data provide further evidence that leptin signaling in POMC neurons plays an important in leptin's ability to regulate glucose metabolism.”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [88]
Citations
Cites
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Abnormal splicing of the leptin receptor in diabetic mice
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“In further support of this, deletion of ObRb in the ventromedial hypothalamus (VMH) in 12 wks old mice increases body weight by ~10% and a combined loss in POMC and VMH neurons increases weight by 25%, suggesting additive effects (Dhillon et al., 2006).”
Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice
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“In addition, intracerebroventricular leptin can acutely stimulate glucose uptake in skeletal muscle (Cusin et al., 1998; Haque et al., 1999; Kamohara et al., 1997; Minokoshi et al., 1999) and inhibit hepatic glucose production (Pocai et al.”
Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity
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“Consistent with this, leptin receptor mRNA is densely expressed in the ARC of mice and rats (Elmquist et al., 1998; Mercer et al., 1996),”
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“Furthermore, unilateral, not bilateral, restoration of endogenous leptin receptors in arcuate neurons of leptin-receptor deficient mice (Coppari et al., 2005) results in a phenotype strikingly similar to that of our HA-ObRb/Pomc-Cre/Leprdb/db mice.”
InfluentialRegulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice
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“HA-ObRb/Pomc-Cre/Leprdb/db mice had modestly increased hypothalamic POMC mRNA (Figure 6A) consistent with a role of leptin signaling to stimulate Pomc gene expression (Munzberg et al., 2003; Thornton et al., 1997).”
Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus
van den Top, M., Lee, K., Whyment, A. D., Blanks, A. M., & Spanswick, D. (2004) · Nature Neuroscience · doi:10.1038/nn1226 · Cited by 435
Central melanocortin receptors regulate insulin action
Obici, S., Feng, Z., Tan, J., Liu, L., Karkanias, G. B., & Rossetti, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12954 · Cited by 370 · cited 1×
“In addition, ventricular infusion of α-MSH into rats enhances acute insulinstimulated peripheral glucose uptake and reduces hepatic glucose production, while a melanocortin receptor antagonist exerts opposite effects (Obici et al., 2001).”
Central melanocortin receptors regulate insulin action
Obici, S., Feng, Z., Tan, J., Liu, L., Karkanias, G., & Rossetti, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200112954 · Cited by 370
A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors
Ste. Marie, L., Miura, G. I., Marsh, D. J., Yagaloff, K., & Palmiter, R. D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220409497 · Cited by 366
van de Wall, E., Leshan, R., Xu, A. W., Balthasar, N., Coppari, R., Liu, S. M., Jo, Y. H., MacKenzie, R. G., Allison, D. B., Dun, N. J., et al. (2008) · Endocrinology · doi:10.1210/en.2007-1132 · Cited by 338
Münzberg, H., Huo, L., Nillni, E. A., Hollenberg, A. N., & Bjørbæk, C. (2003) · Endocrinology · doi:10.1210/en.2002-221037 · Cited by 328
Self-citationMinokoshi, Y., Haque, M. S., & Shimazu, T. (1999) · Diabetes · doi:10.2337/diabetes.48.2.287 · Cited by 302 · cited 1×
“In addition, intracerebroventricular leptin can acutely stimulate glucose uptake in skeletal muscle (Cusin et al., 1998; Haque et al., 1999; Kamohara et al., 1997; Minokoshi et al., 1999) and inhibit hepatic glucose production (Pocai et al.”
The Central Melanocortin System Can Directly Regulate Serum Insulin Levels*
Fan, W., Dinulescu, D. M., Butler, A. A., Zhou, J., Marks, D. L., & Cone, R. D. (2000) · Endocrinology · doi:10.1210/endo.141.9.7665 · Cited by 294
Regulation of Pancreatic β Cell Mass by Neuronal Signals from the Liver
Imai, J., Katagiri, H., Yamada, T., Ishigaki, Y., Suzuki, T., Kudo, H., Uno, K., Hasegawa, Y., Gao, J., Kaneko, K., et al. (2008) · Science · doi:10.1126/science.1163971 · Cited by 235 · cited 1×
“Whether the increased islet mass is a direct result of leptin action via POMC neurons and CNS regulation (Imai et al., 2008), or is an indirect consequence of altered metabolic state or incretin action (Karaca et al.”
Tang-Christensen, M., Vrang, N., Ortmann, S., Bidlingmaier, M., Horvath, T. L., & Tschöp, M. (2004) · Endocrinology · doi:10.1210/en.2004-0529 · Cited by 226 · cited 1×
“, 2005) and recombinant AgRP decreases locomotor activity in normal mice (Tang-Christensen et al., 2004), further suggesting a role of the melanocortin pathway.”
Haque, M. S., Minokoshi, Y., Hamai, M., Iwai, M., Horiuchi, M., & Shimazu, T. (1999) · Diabetes · doi:10.2337/diabetes.48.9.1706 · Cited by 215 · cited 2×
“, 2008) through altered autonomic output (Haque et al., 1999).”
The arcuate nucleus as a primary site of satiety effect of leptin in rats
Satoh, N., Ogawa, Y., Katsuura, G., Hayase, M., Tsuji, T., Imagawa, K., Yoshimasa, Y., Nishi, S., Hosoda, K., & Nakao, K. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00163-8 · Cited by 213 · cited 1×
“and injection of leptin directly into the ARC is sufficient to acutely reduce food intake (Satoh et al., 1997).”
Leptin increases energy expenditure and selectively promotes fat metabolism in ob/ob mice
Hwa, J. J., Fawzi, A. B., Graziano, M., Ghibaudi, L., Williams, P., van Heek, M., Davis, H., Rudinski, M. S., Sybertz, E. J., & Strader, C. D. (1997) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1997.272.4.r1204 · Cited by 199 · cited 1×
“This suggests that POMC neurons play a partial role in attenuating food intake by leptin, but have little if any role in leptin’s action to increase energy expenditure (Hwa et al., 1997).”
Cusin, I., Zakrzewska, K. E., Boss, O., Muzzin, P., Giacobino, J. P., Ricquier, D., Jeanrenaud, B., & Rohner-Jeanrenaud, F. (1998) · Diabetes · doi:10.2337/diabetes.47.7.1014 · Cited by 190
Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin
Rahmouni, K., Haynes, W. G., Morgan, D. A., & Mark, A. L. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-14-05998.2003 · Cited by 185 · cited 1×
“Furthermore, the central melanocortin pathway can increase sympathetic drive to peripheral tissues and enhance insulin-dependent glucose disposal (Brito et al., 2007; Heijboer et al., 2005; Rahmouni et al., 2003).”
Brito, M. N., Brito, N. A., Baro, D. J., Song, C. K., & Bartness, T. J. (2007) · Endocrinology · doi:10.1210/en.2007-0621 · Cited by 167 · cited 1×
“Furthermore, the central melanocortin pathway can increase sympathetic drive to peripheral tissues and enhance insulin-dependent glucose disposal (Brito et al., 2007; Heijboer et al., 2005; Rahmouni et al., 2003).”
Morton, G. J., Niswender, K. D., Rhodes, C. J., Myers, M. G., Blevins, J. E., Baskin, D. G., & Schwartz, M. W. (2003) · Endocrinology · doi:10.1210/en.2002-0115 · Cited by 158
Alteration of Islet Cell Populations in Spontaneously Diabetic Mice
Baetens, D., Stefan, Y., Ravazzola, M., MALAISSE-LAGAE, F., Coleman, D., & Orci, L. (1978) · Diabetes · doi:10.2337/diab.27.1.1 · Cited by 155
Central Leptin Acutely Reverses Diet-Induced Hepatic Insulin Resistance
Pocai, A., Morgan, K., Buettner, C., Gutierrez-Juarez, R., Obici, S., & Rossetti, L. (2005) · Diabetes · doi:10.2337/diabetes.54.11.3182 · Cited by 153 · cited 1×
“, 1999) and inhibit hepatic glucose production (Pocai et al., 2005; van den Hoek et al., 2008).”
AMP‐activated protein kinase and muscle glucose uptake
Musi, N., & Goodyear, L. J. (2003) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2003.01168.x · Cited by 149
Characterization of Leptin-Responsive Neurons in the Caudal Brainstem
Ellacott, K. L. J., Halatchev, I. G., & Cone, R. D. (2006) · Endocrinology · doi:10.1210/en.2005-0877 · Cited by 132
Agouti-related protein-deficient mice display an age-related lean phenotype
Wortley, K. E., Anderson, K. D., Yasenchak, J., Murphy, A., Valenzuela, D., Diano, S., Yancopoulos, G. D., Wiegand, S. J., & Sleeman, M. W. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.11.004 · Cited by 128 · cited 1×
“In addition, AgRP-deficient mice are hyperactive (Wortley et al., 2005) and recombinant AgRP decreases locomotor activity in normal mice (Tang-Christensen et al.”
Activation of Stat3 Signaling in AgRP Neurons Promotes Locomotor Activity
Mesaros, A., Koralov, S. B., Rother, E., Wunderlich, F. T., Ernst, M. B., Barsh, G. S., Rajewsky, K., & Brüning, J. C. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.01.007 · Cited by 128
Huo, L., Grill, H. J., & Bjørbæk, C. (2006) · Diabetes · doi:10.2337/diabetes.55.03.06.db05-1143 · Cited by 127
Self-citationCannabinoids augment the release of neuropeptide Y in the rat hypothalamus
Gamber, K. M., Macarthur, H., & Westfall, T. C. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.04.017 · Cited by 107
Self-citationFunctional pancreatic beta-cell mass: Involvement in type 2 diabetes and therapeutic intervention
Karaca, M., Magnan, C., & Kargar, C. (2009) · Diabetes & Metabolism · doi:10.1016/j.diabet.2008.09.007 · Cited by 98 · cited 1×
“, 2008), or is an indirect consequence of altered metabolic state or incretin action (Karaca et al., 2009), remains to be elucidated.”
Sexually different actions of leptin in proopiomelanocortin neurons to regulate glucose homeostasis
Shi, H., Strader, A. D., Sorrell, J. E., Chambers, J. B., Woods, S. C., & Seeley, R. J. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00704.2007 · Cited by 85
Distribution and possible origin of β-endorphin and ACTH in discrete brainstem nuclei of rats
Palkovits, M., & Eskay, R. L. (1987) · Neuropeptides · doi:10.1016/0143-4179(87)90051-5 · Cited by 77
Skeletal muscle and insulin sensitivity: pathophysiological alterations
Ryder, J. (2001) · Frontiers in bioscience · doi:10.2741/ryder · Cited by 73 · cited 1×
“Exercise training increases insulin-sensitivity and improves glucose homeostasis (Hespel et al., 1996; Ryder et al., 2001).”
N-acetylation of hypothalamic α-melanocyte-stimulating hormone and regulation by leptin
Guo, L., Münzberg, H., Stuart, R. C., Nillni, E. A., & Bjørbæk, C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403165101 · Cited by 71
Self-citationTanaka, T., Masuzaki, H., Yasue, S., Ebihara, K., Shiuchi, T., Ishii, T., Arai, N., Hirata, M., Yamamoto, H., Hayashi, T., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.04.004 · Cited by 62 · cited 1×
“In addition, central administration of melanocortin receptor agonists is sufficient to activate muscle AMPK phosphorylation in mice (Tanaka et al., 2007).”
Influence of Dietary Carbohydrate on the Induction of Diabetes in C57BL/KsJ-db/db Diabetes Mice
Leiter, E. H., Coleman, D. L., Ingram, D. K., et al. (1983) · Journal of Nutrition · doi:10.1093/jn/113.1.184 · Cited by 54 · cited 1×
“Leptin receptors in POMC neurons of Leprdb/db mice increases islet mass Pancreatic islets in Leprdb/db mice have altered morphology and impaired function (Baetens et al., 1978; Leiter et al., 1983).”
Heijboer, A. C., van den Hoek, A. M., Pijl, H., Voshol, P. J., Havekes, L. M., Romijn, J. A., & Corssmit, E. P. M. (2005) · Diabetologia · doi:10.1007/s00125-005-1838-8 · Cited by 43 · cited 1×
“Furthermore, the central melanocortin pathway can increase sympathetic drive to peripheral tissues and enhance insulin-dependent glucose disposal (Brito et al., 2007; Heijboer et al., 2005; Rahmouni et al., 2003).”
Leptin Deficiency Per Se Dictates Body Composition and Insulin Action in ob/ob Mice
Van Den Hoek, A. M., Teusink, B., Voshol, P. J., Havekes, L. M., Romijn, J. A., & Pijl, H. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01626.x · Cited by 34
Significance of insulin for glucose metabolism in skeletal muscle during contractions
Hespel, P., Vergauwen, L., Vandenberghe, K., & Richter, E. A. (1996) · Diabetes · doi:10.2337/diab.45.1.s99 · Cited by 22
Elmquist (1998) · doi:10.1002/(sici)1096-9861(19980615)395:4
Self-citation
Cited by
Sorted by citations
Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism
Park, H. K., & Ahima, R. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.08.004 · Cited by 710
“Moreover, selective expression of LepRb in hypothalamic POMC neurons prevents diabetes in LepR-deficient db/db mice, independently of changes in food intake and weight [105, 106, 108].”
Zhan, C., Zhou, J., Feng, Q., Zhang, J.-E., Lin, S., Bao, J., Wu, P., & Luo, M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2742-12.2013 · Cited by 470
“Selective expression of the leptin receptor in brain POMC neurons increases the activity level of the db/db mice that lack functional leptin receptors (Huo et al., 2009).”
Garland, T., Schutz, H., Chappell, M. A., Keeney, B. K., Meek, T. H., Copes, L. E., Acosta, W., Drenowatz, C., Maciel, R. C., van Dijk, G., et al. (2011) · Journal of Experimental Biology · doi:10.1242/jeb.048397 · Cited by 444
“mediates locomotor activity (Huo et al., 2009).”
Varela, L., & Horvath, T. L. (2012) · The EMBO Reports · doi:10.1038/embor.2012.174 · Cited by 426
“The deletion or overexpression of LepR in POMC or AgRP neurons causes changes in body weight, food intake and glucose homeostasis [44–46].”
InfluentialFrom neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior
Williams, K. W., & Elmquist, J. K. (2012) · Nature Neuroscience · doi:10.1038/nn.3217 · Cited by 435
Metadata
- Authors
- Huo, L., Gamber, K., Greeley, S., Silva, J., Huntoon, N., Leng, X.-H., & Bjørbæk, C.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Baylor College of Medicine (US)
- Corresponding author
- Bjørbæk, Christian
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 9
- Issue
- 6
- Pages
- 537-547
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2730605
- OpenAlex
- W2094751859
- Semantic Scholar
- 95ea91daad2a28a34aff2806aa0df0859b58178d
- Cited by
- 226
- References
- 63
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 10 · 2022: 5 · 2021: 13 · 2020: 12 · 2019: 8 · 2018: 11 · 2017: 20 · 2016: 16 · 2015: 19 · 2014: 15 · 2013: 16 · 2012: 20
- FWCI
- 9.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- Richard and Susan Smith Family Foundation
- National Institute of Diabetes and Digestive and Kidney Diseases (DK65743, DK60673, P30DK046200, R01DK060673, R01DK065743, DK46200.)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- leptin, POMC neurons, glucose homeostasis, locomotor activity, leptin receptor, db/db mice, obesity, diabetes mellitus, energy balance, energy intake, body weight
- MeSH terms
- Animals, Blood Glucose, Body Weight, Eating, Motor Activity, Neurons, Pro-Opiomelanocortin, Signal Transduction, Mice, Knockout, Leptin, Mice, Receptors, Leptin
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