Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action

Abstract

The regulation of body weight and composition involves input from genes and the environment, demonstrated, for example, by the variable susceptibility of inbred strains of mice to obesity when offered a high-fat diet. The identification of the gene responsible for obesity in the ob/ob mouse provides a new approach to defining links between diet and genetics in the regulation of body weight. The ob gene protein product, leptin, is an adipocyte-derived circulating protein. Administration of recombinant leptin reduces food intake and increases energy expenditure in ob/ob mice, suggesting that it signals to the brain the magnitude of fat stores. Information on the regulation of this protein is limited. In several rodent models of obesity including db/db, fa/fa, yellow (Ay/a) VMH-lesioned, and those induced by gold thioglucose, monosodium glutamate, and transgenic ablation of brown adipose tissue, leptin mRNA expression and the level of circulating leptin are increased, suggesting resistance to one or more of its actions. We have assessed the impact of increased dietary fat on circulating leptin levels in normal FVB mice and FVB mice with transgene-induced ablation of brown adipose tissue. We find that high-fat diet evokes a sustained increase in circulating leptin in both normal and transgenic mice, with leptin levels accurately reflecting the amount of body lipid across a broad range of body fat. However, despite increased leptin levels, animals fed a high-fat diet became obese without decreasing their caloric intake, suggesting that a high content of dietary fat changes the 'set point' for body weight, at least in part by limiting the action of leptin.

Obesity and related consequences to ageing

“…Lean individuals with small adipocytes are metabolically homeostatic, but enlarged adipocytes in overweight or obese subjects promote inflammation due to macrophage recruitment. In parallel with fat mass enlargement, as the metabolic role of adipocytes changes, the secretion of various hormones, such as adiponectin, is affected (Ukkola and Santaniemi 2002;Frederich et al 1995). Since adiponectin naturally decreases with age and obesity accelerates the decline in adiponectin levels, one may speculate that obesity alters the ageing process through adiponectin regulation.…”

“…Recent studies have shown that although the complete absence of leptin leads to obesity (Ahima and Flier 2000;Zhang et al 1994), leptin at excessive levels does not prompt a lean phenotype (Ahima and Flier 2000;Myers et al 2012). Leptin expression occurs at high levels in animal models of obesity (Frederich et al 1995;Sinha et al 1996) and in human obesity (Lonnqvist et al 1995). This phenomenon is called leptin resistance and is described as a reduced sensitivity with respect to the anorectic response to exogenously administered leptin (Carter et al 2013).…”

RNA-seq profiles from grass carp tissues after reovirus (GCRV) infection based on singular and modular enrichment analyses

“…Leptin is primarily an important regulator of energy intake and metabolic rate (Frederich et al, 1995). When leptin activates the adipocytokine pathway, several neuropeptides are released that bring about an anorectic effect.…”

Nutrition-induced differences in body composition, compensatory growth and endocrine status in growing pigs ,

“…The role of adipostat is based on the strong association between leptin gene expression, circulating leptin levels, and body fat content across animals of different genotypes (Frederich et al, 1995;McDougald et al, 1995). Leptin receptors are present in the hypothalamus (Chua et al, 1996), and increases in plasma leptin concentrations have been shown to inhibit feed intake, reduce Ld, and increase metabolic rate (Campfield et al, 1995;Halaas et al, 1997).…”