Butyrate regulates leptin expression through different signaling pathways in adipocytes

Leptin is an adipocytokine that regulates body weight, and maintains energy homeostasis by promoting reduced food intake and increasing energy expenditure. Leptin expression and secretion is regulated by various factors including hormones and fatty acids. Butyrate is a short-chain fatty acid that acts as source of energy in humans. We determined whether this fatty acid can play a role in leptin expression in fully differentiated human adipocytes. Mature differentiated adipocytes were incubated with or without increasing concentrations of butyrate. RNA was extracted and leptin mRNA expression was examined by Northern blot analysis. Moreover, the cells were incubated with regulators that may affect signals which may alter leptin expression and analyzed with Northern blotting. Butyrate stimulated leptin expression, and stimulated mitogen activated protein kinase (MAPK) and phospho-CREB signaling in a time-dependent manner. Prior treatment of the cells with signal transduction inhibitors as pertusis toxin, Gi protein antagonist, PD98059 (a MAPK inhibitor), and wortmannin (a PI3K inhibitor) abolished leptin mRNA expression. These results suggest that butyrate can regulate leptin expression in humans at the transcriptional level. This is accomplished by: 1) Gi protein-coupled receptors specific for short-chain fatty acids, and 2) MAPK and phosphatidylinositol-3-kinase (PI3K) signaling pathways.

A Prospective Study on Changes of Serum Leptin and Its Expression in CAPD Patients / 대한신장학회잡지

The ob gene product leptin is thought to be an adipostatic hormone through the regulation of food intake and energy expenditure. There are many reports that serum leptin concentration was increased in CRF patients, especially CAPD patients. The causes of elevated serum leptin concentration in CRF are believed to be multifactorial. Increased body fat mass, decreased residual renal function, active inflammation and hyperinsulinemia all are suggested to influence serum leptin concentration in CAPD patients. In this study, in order to investigate the pathogenic mechanism of increased serum leptin level in CAPD patients, we observed the changes of serum leptin concentration, leptin expression in the abdominal subcutaneous fat tissue, body fat composition, residual renal function, serum insulin concentration and CRP. Thirteen patients(7 men and 6 women, mean age 53+/-14 years) were enrolled in this study. Serum leptin concentration was measured by RIA before start of CAPD(baseline data), 5 days and 1, 3 months after start of CAPD. Simultaneously, fat tissues were aspirated from the abdominal subcutaneous fat tissues for analysis of ob gene expression. Ob mRNA expression was measured by semiquantitative RT-PCR method. The changes of serum insulin concentration, C-reactive protein, residual renal function were measured. All studies were done immediately before starting CAPD, 5 days, 1 month and 3 months after starting CAPD. Total body fat was estimated by dual energy X-ray absorptiometry and abdominal visceral and parietal fat area measured by computed tomography were done at 1-3 days(baseline data), 1 month, 3 months after start of CAPD. Serum leptin concentration increased significantly as early as 5 days after start of CAPD and maintained high up to 3 months(4.3+/-2.6->8.2+/-7.6->7.4+/-6.5->10.8+/-13.8ng/mL), while leptin expression in the abdominal subcutaneous fat tissue did not change during the study period(0.24+/-0.06->0.25+/-0.08->0.20+/-0.07->0.34+/-0.21ng/mL). No significant changes of body fat composition, residual renal function and serum insulin concentration were observed during the study period. These results suggest that increase of serum leptin concentration after CAPD may be due to increase of local leptin production, especially from the peritoneum, as has also been suggested by several reports of relatively higher dialysate leptin.