Changes in environmental temperature influence leptin responsiveness in low- and high-fat-fed mice

Harris, Ruth B. S.; Mitchell, Tiffany D.; Kelso, E.W.; Flatt, William P.

doi:10.1152/ajpregu.00848.2006

Cited by 15 publications

(10 citation statements)

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“…A key feature of cold-induced thermogenesis in normal animals is the increase in food intake that occurs over and above the increase in food intake necessary to support nutrition [33–36]; as exemplified by the remarkable boost in food intake that occurs in lactating females exposed to the cold [26]. This suggests that central mechanisms controlling food intake, as related to nutrition, growth and body composition, may be independent of those associated with cold-induced thermogenesis.…”

Section: Discussionmentioning

confidence: 99%

Npvf: Hypothalamic Biomarker of Ambient Temperature Independent of Nutritional Status

et al. 2015

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The mechanism by which mice, exposed to the cold, mobilize endogenous or exogenous fuel sources for heat production is unknown. To address this issue we carried out experiments using 3 models of obesity in mice: C57BL/6J+/+ (wild-type B6) mice with variable susceptibility to obesity in response to being fed a high-fat diet (HFD), B6. Ucp1-/- mice with variable diet-induced obesity (DIO) and a deficiency in brown fat thermogenesis and B6. Lep-/- with defects in thermogenesis, fat mobilization and hyperphagia. Mice were exposed to the cold and monitored for changes in food intake and body composition to determine their energy balance phenotype. Upon cold exposure wild-type B6 and Ucp1-/- mice with diet-induced obesity burned endogenous fat in direct proportion to their fat reserves and changes in food intake were inversely related to fat mass, whereas leptin-deficient and lean wild-type B6 mice fed a chow diet depended on increased food intake to fuel thermogenesis. Analysis of gene expression in the hypothalamus to uncover a central regulatory mechanism revealed suppression of the Npvf gene in a manner that depends on the reduced ambient temperature and degree of exposure to the cold, but not on adiposity, leptin levels, food intake or functional brown fat.

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Section: Discussionmentioning

confidence: 99%

Npvf: Hypothalamic Biomarker of Ambient Temperature Independent of Nutritional Status

et al. 2015

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“…Because the CD rats were tube fed, the increase in body fat mass was independent of a change in food intake, but energy expenditure was inhibited during the light phase in leptin-treated CD rats (18). The increase in body fat of leptin-treated rats is not limited to CD rats, as we had previously reported that a 12-day peripheral infusion of a physiological dose of leptin in mice fed a high-fat diet and housed in a warm environment increased body fat (19). We proposed that, although the high-fat diet prevented a leptin-induced inhibition of food intake, these mice were not totally leptin resistant and, in specific situations when leptin activity in the forebrain was inhibited, body fat would increase due to an inhibition of energy expenditure.…”

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confidence: 73%

“…In a previous study, we reported that high-fat-fed mice receiving peripheral infusions of leptin and housed in a warm environment (27°C) gained body fat mass when compared with their PBS-infused controls (19). We hypothesized that the increase in carcass fat was due to a partial leptin resistance that prevented leptin from reducing food intake and body fat combined with housing in an environment that prevented an increase in energy expenditure.…”

Section: Discussionmentioning

confidence: 98%

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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“…[44][45][46][47] In chronic studies, high-fat-fed mice studied in the TNZ actually gained additional fat when treated with leptin. 44 We are constantly faced with a myriad of variables that influence experimental outcomes, and our control of these conditions contributes to the ultimate validity of the findings. Even in the relatively simple experiment of injecting a drug and measuring a physiological variable, we must know and control T a .…”

Section: Pharmacological Studiesmentioning

confidence: 99%

Phenotyping small animals as models for the human metabolic syndrome: thermoneutrality matters

Overton

2010

Int J Obes

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It is standard practice in preclinical biomedical research to house mammalian model organisms at an ambient temperature substantially below the thermoneutral zone. These experimental studies are performed using animals that are chronically challenged by mild cold stress. This condition increases food intake, metabolic rate, sympathetic activity, blood pressure and heart rate. Furthermore, this condition alters the behavioral and physiological responses to drug administration, energy restriction and overfeeding. This paper will review these observations, which must be understood in the context of phenotyping small mammals to enhance our understanding of the biology of human disease.

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Changes in environmental temperature influence leptin responsiveness in low- and high-fat-fed mice

Cited by 15 publications

References 50 publications

Npvf: Hypothalamic Biomarker of Ambient Temperature Independent of Nutritional Status

Npvf: Hypothalamic Biomarker of Ambient Temperature Independent of Nutritional Status

Leptin-induced increase in body fat content of rats

Phenotyping small animals as models for the human metabolic syndrome: thermoneutrality matters

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