Original Article CD36-Facilitated Fatty Acid Uptake Inhibits Leptin Production and Signaling in Adipose Tissue

Leptin plays an important role in regulating energy expen-diture in response to food intake, but nutrient regulation of leptin is incompletely understood. In this study using in vivo and in vitro approaches, we examined the role of fatty acid uptake in modulating leptin expression and produc-tion. Leptin levels are doubled in the CD36-null mouse, which has impaired cellular fatty acid uptake despite a 40% decrease in fat mass. The CD36-null mouse is protected from diet-induced weight gain but not from that conse-quent to leptin deficiency. Leptin secretion in the CD36-null mouse is strongly responsive to glucose intake, whereas a blunted response is observed in the wild-type mouse. This indicates that leptin regulation integrates opposing influences from glucose and fatty acid and loss of fatty acid inhibition allows unsuppressed stimulation b