Dual regulation of leptin secretion: intracellular energy and calcium dependence of regulated pathway

Rodent leptin is secreted by adipocytes and acutely regulates appetite and chronically regulates body weight. Mechanisms for leptin secretion in cultu red adipocytes were investigated. Acutely, energy-producing substrates stim ulated leptin secretion about twofold. Biologically inert carbohydrates fai led to stimulate leptin secretion, and depletion of intracellular energy in hibited leptin release. There appears to be a correlation between intracell ular ATP concentration and the rate of leptin secretion. Insulin increased leptin secretion by an additional 25%. Acute leptin secretion is calcium de pendent. When incubated in the absence of calcium or in the presence of int racellular calcium chelators, glucose plus insulin failed to stimulate lept in secretion. In contrast, basal leptin secretion is secreted spontaneously and is calcium independent. Adipocytes from fatter animals secrete more le ptin, even in the absence of calcium, compared with cells from thinner anim als. Acute stimulus-secretion coupling mechanisms were then investigated. T he potassium channel activator diazoxide and the nonspecific calcium channe l blockers nickel and cadmium inhibited acute leptin secretion. These studi es demonstrate that intracellular energy production is important for acute leptin secretion and that potassium and calcium flux may play roles in coup ling intracellular energy production to leptin secretion.