Positional cloning of the mouse obese gene and its human homologue

Abstract

The mechanisms that balance food intake and energy expenditure determine who will be obese and who will be lean. One of the molecules that regulates energy balance in the mouse is the obese (ob) gene. Mutation of ob results in profound obesity and type II diabetes as part of a syndrome that resembles morbid obesity in humans. The ob gene product may function as part of a signalling pathway from adipose tissue that acts to regulate the size of the body fat depot.

Interactions between the melanocortin system and the hypothalamo–pituitary–thyroid axis

“…Following the discovery of the adipocyte-derived hormone leptin by Friedman et al in 1994 [69], subsequent studies over the last decade support a role for leptin as a negative feedback signal from the periphery to the central nervous system (CNS) to regulate energy homeostasis (for reviews see [17], 44 ,58]. In addition to its role in regulating body weight, leptin signals to the CNS the transition from the fed to fasted state (for review see [70]).…”

Effect of Central Antileptin Antibody on the Onset of Female Rat Puberty

“…Numerous studies have inferred that leptin may regulate the hypothalamic-pituitary-gonadal axis. One indication that leptin is involved in centrally regulated maturation of the reproductive system was the discovery that ob/ob females are always sterile [6], and weight loss induced by dietary restriction fails to correct their sterility. Importantly, their fertility can be reversed by leptin treatment in both sexes [7, 8].…”

Threading analysis suggests that the obese gene product may be a helical cytokine

“…The product of the mouse ob gene, and its human homolog, is a case in point. Mice that are homozygous for mutations in ob develop morbid obesity and type II diabetes [4]. The ob gene was recently isolated by positional cloning methodologies, and its product found to encode a 167-residue protein that is 84% identical between mice and humans.…”