Leptin production by the stomach is up-regulated in obese (fa/fa) Zucker rats

PICO, CATALINA, JUANA SANCHEZ, PAULA OLIVER, AND ANDREU PALOU. Leptin production by the stomach is up-regulated in obese (falfa) Zucker rats. Obes Res. 2002;10:932-938. Objective: Genetically obese (fa fa) Zucker rats display markedly elevated circulating leptin levels compared with their lean counterparts; this is expected because of the lack of a LepR-mediated feedback inhibition. The aim of this study was to determine the effect of the leptin receptor mutation in the Zucker rat on gastric leptin production and on the response to 14 hours of starvation. The response to a short-term period of food intake (20 minutes) on gastric leptin release was also analyzed. Research Methods and Procedures: Leptin mRNA expression in the gastric mucosa and in adipose tissue depots (epididymal, retroperitoneal, mesenteric, and inguinal) was assessed by reverse transcriptase-polymerase chain reaction and serum and stomach leptin content by enzyme-linked immunosorbent assay. Results: Obese Zucker rats overexpressed leptin in the stomach. They overexpress leptin in the inguinal adipose tissue but not in visceral adipose tissue depots, indicating tissue-specific obesity-dependent differences. Gastric leptin expression is regulated by feeding conditions in lean but not in obese (falfa) rats. In lean animals, leptin mRNA levels decrease in fasting conditions and increase rapidly with a short period of food intake. Obese Zucker rats also overdisplay stomach leptin levels. Feeding acutely stimulates leptin secretion by the stomach in lean, and to a lesser extent, in obese rats. Discussion: These results indicate impaired regulation of leptin expression in the stomach of obese (fa/fa) Zucker rats. However, there is still an effect of the nutritional status on gastric leptin levels despite the lack of a functional leptin receptor.