PYY(3–36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity

Vrang, Niels; Madsen, Andreas Nygaard; Tang-Christensen, Mads; Hansen, Gitte; Larsen, Philip J.

doi:10.1152/ajpregu.00726.2005

Cited by 123 publications

(86 citation statements)

References 32 publications

(55 reference statements)

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“…This is consistent with our previous findings that PYY knockout animals are equally glucose tolerant but hyperinsulinemic after a glucose challenge ( Boey et al, 2006b) and further supports an important long-term role for PYY in regulating glucose homeostasis. Moreover, as low PYY levels are associated with increased insulin secretion and insulin resistance in humans (Boey et al, 2006a), enhanced expression of PYY may improve glucose homeostasis and insulin sensitivity, in keeping with findings from others ( van den Hoek et al, 2004 andVrang et al, 2006).…”

Section: Pyytg/ob Mice Exhibit Improved Glucose Tolerancesupporting

confidence: 87%

PYY transgenic mice are protected against diet-induced and genetic obesity

et al. 2008

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The gut-derived hormone, peptide YY (PYY) reduces food intake and enhances satiety in both humans and animals. Obese individuals also have a deficiency in circulating peptide YY, although whether this is a cause or a consequence of obesity is unclear. Our aims were to determine whether peptide YY (PYY) over-expression may have therapeutic effects for the treatment of obesity by altering energy balance and glucose homeostasis. We generated PYY transgenic mice and measured body weight, food intake, temperature, adiposity, glucose tolerance, circulating hormone and lipid concentrations and hypothalamic neuropeptide levels (neuropeptide Y; proopiomelanocortin, and thyrotropin-releasing hormone) under chow and high-fat feeding and after crossing these mice onto the genetically obese leptin-deficient ob/ob mouse background. PYY transgenic mice were protected against diet-induced obesity in association with increased body temperature (indicative of increased thermogenesis) and sustained expression of thyrotropin-releasing hormone in the paraventricular nucleus of the hypothalamus. Moreover, PYY transgenic mice crossed onto the genetically obese ob/ob background had significantly decreased weight gain and adiposity, reduced serum triglyceride levels and improved glucose tolerance compared to ob/ob controls. There was no effect of PYY transgenic over expression on basal or fastinginduced food intake measured at 11-12 weeks of age. Together, these findings suggest that long-term administration of PYY, PYY-like compounds or agents that stimulate PYY synthesis in vivo can reduce excess adiposity and improve glucose tolerance, possibly via effects on the hypothalamo-pituitary-thyroid axis and thermogenesis.

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Section: Pyytg/ob Mice Exhibit Improved Glucose Tolerancesupporting

confidence: 87%

PYY transgenic mice are protected against diet-induced and genetic obesity

et al. 2008

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“…Our data suggest that elevating PYY levels may have a long-term effect in reducing appetite, particularly in suppressing the enhanced appetite induced by a period of energy deficit. It is noteworthy that the effect of chronic peripheral PYY3-36 administration to reduce spontaneous food intake is transient, lasting only for the first few days of administration (Adams et al, 2006, Vrang et al, 2006, Ortiz et al, 2007and van den Hoek et al, 2007. Y receptor down-regulation due to constant stimulation by continuously elevated PYY is suggested to contribute to transient feeding responses to continuous administrations of PYY3-36 (Chelikani et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Adult-onset PYY overexpression in mice reduces food intake and increases lipogenic capacity

et al. 2012

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Peptide YY (PYY) is best known for its important role in appetite regulation, but recent pharmacological studies have suggested that PYY is also involved in regulating energy balance and glucose homeostasis. However, the mechanism behind the regulation of these parameters by PYY is less clear. Here, by utilising an inducible transgenic mouse model where PYY overexpression is induced in adult animals (PYYtg) and release of mature PYY peptides is controlled by endogenous machineries, we show that elevating PYY levels leads to reduced food intake after a 24-h fast. Furthermore, PYYtg mice, although not significantly different from WT with respect to body weight, adiposity, lean mass, physical activity or energy expenditure, exhibited a significantly increased respiratory exchange ratio (RER), indicating decreased lipid oxidation and/or increased lipogenesis. Importantly, PYYtg mice showed a 25% reduction in liver protein levels of phosphorylated acetyl-CoA carboxylase (pACC) in the absence of changes in total ACC levels compared to those of WT mice. Moreover, liver protein levels of AMP-activated kinase (AMPK) in PYYtg mice were 25% lower than those of WT mice, consistent with a reduced pACC in these mice. These data suggest that elevation of PYY levels as seen after a meal can increase lipogenic capacity, which is likely a key contributor to the increased RER seen in PYYtg mice. In addition, PYYtg mice exhibited comparable insulin tolerance and oral glucose tolerance to those of WT, but showed a trend towards decreased insulin levels in response to an oral glucose challenge, indicating that PYY could improve insulin action. Taken together, these findings demonstrate that under physiological conditions, PYY reduces food intake while enhancing lipogenic capacity and insulin action, likely contributing to fuel assimilation in the postprandial state.

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“…In general, the currently available DIO rodent models are all based on the feeding of mice or rats diets that are high in energy, mostly from fat (eg, the Levin DIO, the C57BL/6J DIO) or sugar [7,25,26] . Once obesity has been induced, the animals exhibit stabilized body weights, marked visceral adiposity (30%-35% fat), high plasma levels of leptin, moderate insulin resistance (rather than overt diabetes) and …”

Section: Wwwnaturecom/aps Hansen G Et Almentioning

confidence: 99%

Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats

2012

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Aim: To validate the gubra DIO-rats as a useful animal model of human obesity. Methods: The gubra diet-induced obesity (DIO) rat model was based on male Sprague-Dawley rats with ad libitum access to regular chow and a palatable diet rich in fat and sugar. To evaluate the versatility of the gubra DIO-rats as a valid model of human obesity syndrome, the efficacy of 2 weight loss compounds liraglutide and sibutramine with different mechanisms of action were examined in 7-month-old gubra DIO-rats. Liraglutide (200 µg/kg, sc) was administered bi-daily, and sibutramine (5 mg/kg, po) was administered once daily for 23 d. Results: Both the compounds effectively reduced the food intake, body weight and total fat mass as measured by nuclear magnetic resonance. Whereas the 5-HT reuptake inhibitor/5-HT receptor agonist sibutramine reduced the intake of both chow and the gubradiet, the GLP-1 analogue liraglutide predominantly reduced the intake of the highly palatable diet, indicating a shift in food preference. Sibutramine lowered the insulin sensitivity index, primarily via reductions in glucose-stimulated insulin secretion. Conclusion: This animal model responds well to 2 weight loss compounds with different mechanisms of action. Moreover, the gubra DIO-rat can be particularly useful for the testing of compounds with potential effects on diet preference.

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PYY(3–36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity

Cited by 123 publications

References 32 publications

PYY transgenic mice are protected against diet-induced and genetic obesity

PYY transgenic mice are protected against diet-induced and genetic obesity

Adult-onset PYY overexpression in mice reduces food intake and increases lipogenic capacity

Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats

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