Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PL01

Poster Communications

Remote control of hypothalamic circuits controlling food intake and metabolism

J. Friedman1

1. Rockefeller University, New York, New York, United States.


The discovery of leptin has led to the elucidation of a robust physiologic system that maintains fat stores at a relatively constant level. Leptin is a peptide hormone secreted by adipose tissue in proportion to its mass. This hormone circulates in blood and acts on the hypothalamus to regulate food intake and energy expenditure. When fat mass falls, plasma leptin levels fall stimulating appetite and suppressing energy expenditure until fat mass is restored. When fat mass increases, leptin levels increase, suppressing appetite until weight is lost. By such a mechanism total energy stores are stably maintained within a relatively narrow range. Recessive mutations in the leptin gene are associated with massive obesity in mice and some humans. Treatment with recombinant leptin markedly reduces food intake and body weight. The low leptin levels in patients with leptin mutations are also associated with multiple abnormalities including infertility, diabetes and immune abnormalities all of which are corrected by leptin treatment. These findings have established important links between energy stores and many other physiologic systems and led to the use of leptin as a treatment for an increasing number of other human conditions including a subset of obesity, some forms of diabetes including lipodystrophy and hypothalamic amennorhea, the cessation of menstruation seen in extremely thin women. Identification of a physiologic system that controls energy balance establishes a biologic basis for obesity Leptin has recently been approved for the treatment of lipodystrophy , a severe form of diabetes associated with reduced fat mass and low endogenous leptin levels. These and other data have suggested that leptin can reduce glucose and lower insulin independent of effects on food intake. Further evidence suggests that leptin's effects on glucose metabolism are mediated by the hypothalamus. Recent studies have focused on the role of specific populations of glucose sensing neurons in the ventromedial and lateral hypothalamus. These studies have employed a novel technology for modulating neural activity using radiowaves or magnets. The results of these studies have highlighted the critical role of the CNS to control blood glucose and the levels of pancreatic hormones.

Where applicable, experiments conform with Society ethical requirements