D. V. Rayner

Introduction of a high-energy diet acutely up-regulates hypothalamic cocaine and amphetamine-regulated transcript, Mc4R and brown adipose tissue uncoupling protein-1 gene expression in male Sprague-Dawley rats.

Obesity is an escalating problem in Western societies. Susceptibility to weight gain within an obesogenic environment is variable. It remains unclear how the range of weight gain responses are generated. It is possible that an individuals immediate and/or sustained appetite for apparently palatable foods, or metabolic adaptations to a new diet could be important. The present study therefore examined the short‐ to medium‐term effects of a high‐energy (HE) diet on bodyweight, food intake, and energy balance‐related signalling systems. Sprague‐Dawley rats were fed either chow or an HE diet for 12 h, 24 h, 48 h or 14 days. Blood hormones and metabolites were assayed, and expression of uncoupling protein‐1 (UCP‐1) and hypothalamic energy‐balance related genes were determined by Northern blotting or in situ hybridisation, respectively. Short‐term exposure (12 h, 24 h, 48 h) to the HE diet had no effect on grams of food consumed, but caloric intake was increased. Exposure to HE diet for 14 days (medium term) established a bodyweight differential of 7.7 g, and animals exhibited a transient increase in caloric intake of 5 days duration. Terminal levels of leptin, insulin, glucose and non‐esterified fatty acids (NEFAs) were all increased in HE‐fed animals. UCP‐1 mRNA was elevated in interscapular brown adipose tissue from HE‐fed rats only at 12 h. Cocaine and amphetamine‐regulated transcript (CART) and Mc4R gene expression in the hypothalamus were increased after 12 h and 24 h on an HE diet, respectively. The rats appear to passively over‐consume calories as a result of consuming a similar weight of a more energy dense food. This evokes physiological responses, which adjust caloric intake over several days. Circulating NEFA and insulin concentrations, UCP‐1, Mc4R and CART gene expression are increased as an immediate consequence of consuming HE diet, and may be involved in countering hypercaloric intake. Circulating leptin is increased in the HE‐fed animals after 48 h, reflecting their increasing adiposity.

Hormonal and neuroendocrine regulation of energy balance‐the role of leptin

A new dimension to the regulation of energy balance has come from the identification of the ob (obese) gene and its protein product, leptin. Leptin is produced primarily in white adipose tissue, but synthesis also occurs in brown fat and the placenta. Several physiological functions have been described for leptin the inhibition of food intake, the stimulation/maintenance of energy expenditure, as a signal of energy reserves to the reproductive system, and as a factor in haematopoiesis. The production of leptin by white fat is influenced by a number of factors, including insulin and glucocorticoids (which are stimulatory), and fasting, cold exposure and beta-adrenoceptor agonists (which are inhibitory). A key role in the regulation of leptin production is envisaged for the sympathetic nervous system, operating through beta 3-adrenoceptors. The leptin receptor gene is expressed in a wide range of tissues, and several splice variants are evident. A long form variant (Ob-Rb) with an intracellular signalling domain is found particularly in the hypothalamus. Leptin exerts its central effects through neuropeptide Y, and through the glucagon-like peptide-1 and melanocortin systems, but it may also interact with other neuroendocrine pathways. The role and function of the leptin system in agricultural animals has not been established, but it offers a potential new target for the manipulation of body fat.