Changes in glucose tolerance and leptin responsiveness of rats offered a choice of lard, sucrose, and chow

Harris, Ruth B. S.; Apolzan, John W.

doi:10.1152/ajpregu.00477.2011

Cited by 37 publications

(50 citation statements)

References 66 publications

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“…5) indicates that LXR regulates UCP-1 activity differently in WAT and BAT. The discrepancy between mRNA level and protein level of UCP-1 may be caused by posttranscriptional regulation as proposed by previous studies (30,31).…”

Section: Discussionmentioning

confidence: 68%

The Liver X Receptor Agonist T0901317 Protects Mice from High Fat Diet-Induced Obesity and Insulin Resistance

Gao

Liu

2012

AAPS J

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Abstract. The effect of activation of liver X receptor by N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1(trifluoromethyl)ethyl]phenyl] benzenesulfonamide (T0901317) on high fat diet (HFD)-induced obesity and insulin resistance was examined in C57BL/6 mice. When on HFD continuously for 10 weeks, C57BL/6 mice became obese with an average body weight of 42 g, insulin resistant, and glucose intolerant. Twice weekly intraperitoneal injections of T0901317 at 50 mg/kg in animals on the same diet completely blocked obesity development, obesity-associated insulin resistance, and glucose intolerance. Quantitative real-time PCR analysis showed that T0901317-treated animals had significantly higher mRNA levels of genes involved in energy metabolism, including Ucp-1, Pgc1a, Pgc1b, Cpt1a, Cpt1b, Acadm, Acadl, Aox, and Ehhadh. Transcription activation of Cyp7a1, Srebp-1c, Fas, Scd-1, and Acc-1 genes was also seen in T0901317-treated animals. T0901317 treatment induced reversible aggregation of lipids in the liver. These results suggest that liver X receptor could be a potential target for prevention of obesity and obesity-associated insulin resistance.

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Section: Discussionmentioning

confidence: 68%

The Liver X Receptor Agonist T0901317 Protects Mice from High Fat Diet-Induced Obesity and Insulin Resistance

Gao

Liu

2012

AAPS J

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“…We cannot exclude the possibility that central GLP-1 resistance results from chronic intake of sucrose. Chronic sucrose consumption results in leptin resistance (19,51). Given the interaction between central leptin and GLP-1 action (16,46,48), it is possible that sucrose feeding impairs the anorectic effects of GLP-1 indirectly via modulation of leptin action.…”

Section: E683mentioning

confidence: 99%

Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose

Burmeister

Ayala

Drucker

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Burmeister MA, Ayala J, Drucker DJ, Ayala JE. Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose. Am J Physiol Endocrinol Metab 304: E677-E685, 2013. First published January 22, 2013 doi:10.1152/ajpendo.00446.2012.-Glucagon-like peptide-1 (GLP-1) suppresses food intake via activation of a central (i.e., brain) GLP-1 receptor (GLP-1R). Central AMP-activated protein kinase (AMPK) is a nutrient-sensitive regulator of food intake that is inhibited by anorectic signals. The anorectic effect elicited by hindbrain GLP-1R activation is attenuated by the AMPK stimulator AICAR. This suggests that central GLP-1R activation suppresses food intake via inhibition of central AMPK. The present studies examined the mechanism(s) by which central GLP-1R activation inhibits AMPK. Supporting previous findings, AICAR attenuated the anorectic effect elicited by intracerebroventricular (icv) administration of the GLP-1R agonist exendin-4 (Ex-4). We demonstrate that Ex-4 stimulates glycolysis and suppresses AMPK phosphorylation in a glucose-dependent manner in hypothalamic GT1-7 cells. This suggests that inhibition of AMPK and food intake by Ex-4 requires central glucose metabolism. Supporting this, the glycolytic inhibitor 2-deoxyglucose (2-DG) attenuated the anorectic effect of Ex-4. However, icv glucose did not enhance the suppression of food intake by Ex-4. AICAR had no effect on Ex-4-mediated reduction in locomotor activity. We also tested whether other carbohydrates affect the anorectic response to Ex-4. Intracerebroventricular pretreatment with the sucrose metabolite fructose, an AMPK activator, attenuated the anorectic effect of Ex-4. This potentially explains the increased food intake observed in sucrose-fed mice. In summary, we propose a model whereby activation of the central GLP-1R reduces food intake via glucose metabolism-dependent inhibition of central AMPK. We also suggest that fructose stimulates food intake by impairing central GLP-1R action. This has significant implications given the correlation between sugar consumption and obesity.glucagon-like peptide 1; adenosine 5=-monophosphate-activated kinase; food intake; glucose; fructose HEALTH RISKS ASSOCIATED WITH OBESITY, including cardiovascular disease, diabetes, and cancer, highlight the importance of understanding mechanisms that control food intake and how they become impaired. Food intake is regulated by neural and hormonal signals that match caloric intake with the chronic and acute energy needs of the organism. Although significant attention has been given to understanding mechanisms associated with adiposity signals such as leptin and insulin, less is known about acute satiety mechanisms regulated by signals such as glucagon-like peptide-1 (GLP-1).GLP-1 is secreted from intestinal L cells in response to nutrient intake and was identified for its ability to stimulate insulin secretion via activation of a pancreatic ␤-cell GLP-1 receptor (GLP-1R) (3). GLP-1 also r...

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“…Coronal 30-m sections were made, and hypothalamic and brain stem phosphorylated signal transducer and activator of transcription-3 (pSTAT3) was detected by immunohistochemistry as described previously (14). The remaining 10 rats (5 per group) were food deprived from 7:00 AM to 11:00 AM, and tissue blocks of the hypothalamus or brain stem were collected for measurement of phosphorylated STAT3, phosphoinositide 3-kinase (pPI3K p85), extracellular signal-related kinases 1/2 (pERK1, pERK2), and AMP-activated protein kinase (pAMPK), suppressor of cytokine signaling 3 (SOCS3), and proteintyrosine phosphatase (PTP1B) by Western blot as described previously (17). All primary antibodies were obtained from Cell Signaling Technology, (Danvers, MA) except anti-PTP1B, which was obtained from Abcam (ab2009; Abcam, Cambridge, MA).…”

Section: Socs3mentioning

confidence: 99%

Leptin-induced increase in body fat content of rats

Harris

2013

American Journal of Physiology-Endocrinology and Metabolism

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Harris RB. Leptin-induced increase in body fat content of rats. Am J Physiol Endocrinol Metab 304: E267-E281, 2013. First published December 4, 2012; doi:10.1152/ajpendo.00251.2012.-We previously reported that peripheral leptin infusions in chronically decrebrate rats, in which the forebrain is neurally isolated from the hindbrain, increased body fat and decreased energy expenditure. Any central leptin response in decerebrate rats would depend upon the hindbrain. Here, we tested whether selective activation of hindbrain leptin receptors increased body fat. Fourth ventricle infusion of 0.6 g leptin/day for 12 days increased body fat by 13% with no increase in food intake. Third ventricle leptin infusions decreased food intake, body fat, and lean tissue with a maximal response at 0.3 g leptin/day. To test whether hindbrain receptors opposed activity of hypothalamic receptors, rats received peripheral infusions of 40 g leptin/day and increasing 4th ventricle doses of the leptin receptor antagonist mutein protein. Mutein (3.0 g/day) reduced body fat in PBS-infused rats to the same level as leptin-infused rats and reduced lean tissue in all rats. Leptin, but not mutein, inhibited food intake. By contrast, 3.0 g/day mutein in the 3rd ventricle increased food intake and body fat in both PBS-and leptin-infused rats. In basal conditions, hindbrain leptin receptors may antagonize activity of forebrain receptors to protect lean and fat tissue, but there is no evidence for an anabolic role for hindbrain receptors when leptin is elevated. In a dietary study, rats increased energy intake when offered lard and 30% sucrose solution in addition to chow. Peripheral leptin infusion exaggerated the gain in body fat without altering energy intake confirming the potential for leptin to increase adiposity.forebrain; hindbrain; mutein leptin; body composition LEPTIN IS AN ADIPOSE-DERIVED HORMONE that is hypothesized to be a negative feedback signal in the regulation of energy balance (46). Central (12, 43) or peripheral (37) administration of leptin inhibits food intake of normal-weight rodents and corrects many aspects of the obesity syndrome in leptin-deficient ob/ob mice (20, 33). The negative energy balance associated with peripheral leptin treatment results in a specific loss of body fat mass and maintenance of lean body mass (20); by contrast, central administration of leptin may result in the loss of both fat and lean tissue (5). Even though leptin is an effective regulator of energy balance in normal-weight rodents, obese or aged animals have high circulating concentrations of endogenous leptin but are leptin resistant because leptin administration does not influence food intake or body weight (7,9,44,45).Early observations that peripheral leptin resistance preceded the development of central leptin resistance in high-fat-fed mice (9) led to the conclusion that peripheral leptin resistance results from a failure of leptin to cross the blood-brain barrier (1), whereas central leptin resistance is a failure of leptin to activate ...

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Changes in glucose tolerance and leptin responsiveness of rats offered a choice of lard, sucrose, and chow

Cited by 37 publications

References 66 publications

The Liver X Receptor Agonist T0901317 Protects Mice from High Fat Diet-Induced Obesity and Insulin Resistance

The Liver X Receptor Agonist T0901317 Protects Mice from High Fat Diet-Induced Obesity and Insulin Resistance

Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose

Leptin-induced increase in body fat content of rats

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