The adipocyte hormone leptin serves as a humoral signal of energy stores, acting on central neuronal networks that regulate ingestive behavior and energy balance. The basis for the circadian rhythm and pulsatility of circulating leptin levels in the face of a relatively stable adipose mass is not known. We have already established the feasibility and validity of adipose tissue microperfusion in humans for measurements of leptin in adipose tissue interstitial fluid. The aim of this study now is to assess the specific aspects of the regulation of adipose tissue metabolism in situ.

The hormone sensitive lipase (HSL) catalyzes the final, rate limiting step of energy mobilization from adipose tissue. Its activation results in hydrolysis of triglycerides, a process referred to as lipolysis. Increased HSL activity during fasting and stress, is physiologically coupled with significant reductions in circulating leptin levels, which in turn, results in increased food intake, and thus, restoration of energy balance. We hypothesize that local neural signals from the sympathetic nervous system to adipocytes through beta-adrenergic receptors simultaneously regulate leptin secretion and lipolysis, the latter via the modulation of HSL activity. This hypothesis will be tested by measurements of interstitial levels of leptin and glycerol in adipose tissue in situ before and after local administration of a beta-adrenergic agonist. Food intake and beta-adrenergic stimulation are excellent potential stimuli in the study of the novel fat-derived hormones, resistin and adiponectin.

We hypothesize that insulin has regulatory effects on leptin secretion and lipolysis. This hypothesis will be tested by measurement of interstitial levels of leptin, TNF-alpha, and interleukin-6 in adipose tissue in situ and after local administration of insulin.