Direct Effect of Ghrelin on Leptin Production by Cultured Rat White Adipocytes

Abstract

GIOVAMBATTISTA, ANDRÉ S, JUDITH PIERMARÍA, MARÍA O. SUESCUN, RICARDO S. CALANDRA, ROLF C. GAILLARD, AND EDUARDO SPINEDI. Direct effect of ghrelin on leptin production by cultured rat white adipocytes. Obesity. 2006;14:19 -27. Objective: Because ghrelin is known to stimulate adipogenesis, we tested whether ghrelin could contribute to the maintenance of homeostasis, directly affecting rat white adipocyte leptin production. Research Methods and Procedures: Isolated retroperitoneal adipocytes were cultured for 0.5 to 48 hours without (baseline) or with (0.001 to 1 nM) ghrelin alone or in combination with insulin (0.01 to 10 nM) or dexamethasone (1 to 100 nM). Adipocytes were also incubated with ghrelin and inhibitors either of RNA (actinomycin D) or protein synthesis (cycloheximide) or with several concentrations (10 to 1000 nM) of a specific ghrelin antagonist. When cultures were terminated, we evaluated adipocyte leptin secretion and ob mRNA expression. Results: Our data indicate that ghrelin directly enhanced adipocyte leptin release and ob mRNA expression, that the leptin-releasing activity of ghrelin was additive to the action of both insulin and dexamethasone and was abrogated by protein synthesis inhibitors, and that effects of ghrelin on adipocyte ob mRNA expression and release were blocked by coincubation with the specific growth hormone secretagogue receptor 1a antagonist. Discussion: Our study supports the ability of ghrelin to enhance white adipose tissue leptin production by a direct receptor-mediated effect. This activity of ghrelin could play a potentially significant role in rapid restoration of homeostasis after food intake.

Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism

“…The circulating levels of leptin were determined by specific RIAs developed in our laboratories (Giovambattista et al, 2006). Serum insulin was assessed by RIA using an anti-rat insulin antibody (Sigma, St. Louis, Missouri, USA) and standard rat insulin provided by Laboratorios Beta (Buenos Aires, Argentina).…”

Excess fructose intake‐induced hypertrophic visceral adipose tissue results from unbalanced precursor cell adipogenic signals

“…Plasma levels of LEP [31], insulin [32] and corticosterone [33] were determined by a specific radioimmunoassay previously developed in our laboratory. Circulating glucose (Wiener Laboratory, Rosario, Argentina) and triglyceride (Wiener Laboratory, Rosario, Argentina) levels were measured using commercial kits.…”

“…LEP concentration in the medium was determined by a specific radioimmunoassay [31]. In this assay, the standard curve ranged between 50 and 12 500 pgÁmL À1 (intra-and inter-assay coefficients of variation of 4-6% and 5-8%, respectively).…”

Endocrine factors in the hypothalamic regulation of food intake in females: a review of the physiological roles and interactions of ghrelin, leptin, thyroid hormones, oestrogen and insulin

“…There is a fine balance between the two physiologically antagonistic hormones as demonstrated by Giovambattista et al (195) , who detected enhanced leptin secretion after prolonged ghrelin exposure. In turn, moderate hyperleptinaemia/ leptin administration prevents the increase of plasma ghrelin during short-term energy restriction (196) .…”