Amylin-Mediated Restoration of Leptin Responsiveness in Diet-Induced Obesity: Magnitude and Mechanisms

Trevaskis, James L.; Coffey, Todd; Cole, Rebecca L.; Lei, Chunli; Wittmer, Carrie; Walsh, B. Timothy; Weyer, Christian; Koda, Joy E.; Baron, Alain; Parkes, David G.; Roth, Jonathan D.

doi:10.1210/en.2008-0770

Cited by 138 publications

(151 citation statements)

References 34 publications

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“…Two amylin doses (5 and 10µg/kg/day) were chosen based on pilot studies, on circulating levels of DIO rats observed in Experiment 1, and on published work [16,22], and were compared to saline infused controls.…”

Section: Experiments Two: Does Chronic Elevation Of Peripheral Amylin mentioning

confidence: 99%

“…It is known that a co-infusion of amylin and leptin reduces body weight and adiposity synergistically in DIO prone rats [22]. Additionally, it has been shown that peripheral administration of amylin restores leptin sensitivity in obese rats and humans [33].…”

Section: Amylin-induced Suppression Of Energy Intake Is Decreased Aftmentioning

confidence: 99%

“…Furthermore, because of the known interaction between amylin and leptin [22,33], we determined whether an increase of amylin, independent of obesity, alters circulating leptin levels. Again we observed that as circulating amylin levels increased, there was a trend toward a decrease in leptin levels.…”

Section: Hyperamylinemia Alone Does Not Cause Amylin Insensitivitymentioning

confidence: 99%

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Influence of high-fat feeding, diet-induced obesity, and hyperamylinemia on the sensitivity to acute amylin

Boyle¹,

Rossier²,

Lutz³

2011

Physiology & Behavior

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Obesity results in the increased secretion of various hormones controlling food intake and body weight, such as leptin, and insulin; increased circulating levels of pancreatic amylin have also been described in obese humans and rodents. Because leptin-resistance is present in diet-induced obese (DIO) rats, and because hyperleptinemia seems necessary for the full development of leptin resistance, we tested whether amylin sensitivity is inversely correlated with adiposity, such that DIO reduces the anorectic action of acute amylin. We also determined if hyperamylinemia leads to a change in amylin sensitivity. In the first experiment, rats were chronically exposed to a high fat (HF; 60% fat) diet or fed standard chow for control. The anorectic response to amylin was tested on several occasions over a 14 week observation period. HF feeding led to the expected increase in body adiposity; the response to an acute amylin injection (5-50 g/kg s.c.) was unaltered for 10 weeks of HF feeding. Even after 12 weeks on a HF diet, which clearly caused obesity, acute administration of amylin (5 g/kg, s.c.) was still able to suppress food intake, although the suppression was not statistically significant. Further experiments using additional doses of amylin will be necessary to demonstrate possible amylin resistance after HF feeding or in DIO rats. In the second experiment, we tested more specifically whether hyperamylinemia that may result from HF feeding and subsequent obesity, reduces the sensitivity of the amylin signaling system. To avoid confounding factors, we chronically infused lean chow fed rats with amylin (5 or 10 g/kg/day s.c.) to elevate their plasma amylin concentration to levels observed in obese rats (30-40 pM). In the absence of obesity, hyperamylinemia did not lead to a reduced sensitivity to acute amylin (5-20 g/kg s.c.) injections; acute amylin reduced eating similarly in all groups of rats. Overall, we concluded that direct diet effects by short term exposure to HF appear to be of little importance for amylin sensitivity; further, long-term maintenance on a HF diet and the resulting obesity only slightly attenuated the anorectic response to acute amylin. Because we observed no marked changes in amylin sensitivity in lean, chow fed rats with induced hyperamylinemia, amylin receptor downregulation in chronic hyperamylinemia does not seem to occur. 1 Long-term maintenance on a HF diet only slightly attenuates acute amylin action.2 Attenuation of amylin action seems more related to obesity than HF exposure.3 Acute amylin sensitivity is not reduced by chronic hyperamylinemia.3 ABSTRACTObesity results in the increased secretion of various hormones controlling food intake and body weight, such as leptin, and insulin; increased circulating levels of pancreatic amylin have also been described in obese humans and rodents. Because leptinresistance is e.g. present in diet-induced obese (DIO) rats, and because hyperleptinemia seems necessary for the full development of leptin resistance, we tested whether amyl...

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Section: Experiments Two: Does Chronic Elevation Of Peripheral Amylin mentioning

confidence: 99%

Section: Amylin-induced Suppression Of Energy Intake Is Decreased Aftmentioning

confidence: 99%

Section: Hyperamylinemia Alone Does Not Cause Amylin Insensitivitymentioning

confidence: 99%

See 1 more Smart Citation

Influence of high-fat feeding, diet-induced obesity, and hyperamylinemia on the sensitivity to acute amylin

Boyle¹,

Rossier²,

Lutz³

2011

Physiology & Behavior

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show abstract

“…81 The effect of the amylin/leptin combination on energy balance appeared to be paralleled by a preferential oxidation of fat as indicated by the low respiratory quotient in both the amylin/leptin and pair-fed groups; 81,[84][85][86] importantly, the lower respiratory quotient was still evident in amylin/leptin coinjected animals during the weight stable phase and not only during weight loss like in the pair-fed group. 81,85,[90][91][92] All effects combined, the amylin/leptin combination treatment prevented the suppression of energy metabolism that is typically seen in situations of negative energy balance which may, for example, be induced by simple dieting.…”

Section: Interactions Of Amylin With Other Factors Involved In the Comentioning

confidence: 95%

“…81 In other words, amylin, which itself is still effective in obese rats, 3,82,83 reduced eating and body weight significantly more when leptin was co-administered with amylin. 81,[84][85][86] The effect of amylin on leptin's action and leptin sensitivity appeared to be specific to amylin 81 because the effects were not seen to the same extent with the GLP-1 analog AC3174, 81 or when infusions of leptin were combined with the GLP-1 receptor agonist exendin-4. 87 Leptin combined with GLP-1 analogs did produce the stronger effects on eating and body weight than single compounds, but the interaction seemed to be (mathematically) additive rather than synergistic.…”

Section: Interactions Of Amylin With Other Factors Involved In the Comentioning

confidence: 99%

Gut hormones such as amylin and GLP-1 in the control of eating and energy expenditure

Lutz

2016

Int J Obes Supp

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Implications of Amylin Receptor Agonism

Roth¹,

Maier²,

Chen³

et al. 2009

Arch Neurol

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Amylin-Mediated Restoration of Leptin Responsiveness in Diet-Induced Obesity: Magnitude and Mechanisms

Cited by 138 publications

References 34 publications

Influence of high-fat feeding, diet-induced obesity, and hyperamylinemia on the sensitivity to acute amylin

Influence of high-fat feeding, diet-induced obesity, and hyperamylinemia on the sensitivity to acute amylin

Gut hormones such as amylin and GLP-1 in the control of eating and energy expenditure

Implications of Amylin Receptor Agonism

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