Leptin is a hormone that acts in the body as a chemical messenger. It is produced in fat
cells and is believed to regulate body weight in humans. Leptin decreases appetite and
influences the energy balance of the body.
This study will attempt to measure levels of leptin production in the fat pad of the body
by using a process called microperfusion. Microperfusion works by inserting 2 to 3 probes
(thin tubes) into the fat pad around the belly button. These probes can measure chemicals
in an area known as the extracellular space. This is the small space between cells and
blood vessels that hormones, medicines, nutrients, and salts travel through.
The study will investigate the effects of a meal, insulin, glucose (sugar), and the
medication isoproterenol on leptin levels. Researchers believe that leptin levels are
regulated along with the enzyme, hormone sensitive lipase (HSL). When hormone sensitive
lipase is activated fat is broken down in a process called lipolysis. In addition,
increased levels of HSL result in decreased levels of leptin, which in turn increases
appetite and food intake.
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.
Healthy subjects ages 18 to 50 years.
Healthy volunteers studied as outpatients.
Minors (less than 18 years of age)
Subjects taking any medication on a regular basis.
Individuals with hepatic, renal, HPA axis or thyroid dysfunction.
Very lean individuals (defined as a body mass index less than 19).
Pregnant or lactating woman.
Individuals with allergies to teflon, polyethylene or skin tape.
Individuals with known allergy to isoproterenol.
Individuals unable to abstain from alcohol, tobacco, tea, and coffee for 18 hours prior
and during the study.