Ontogenesis of leptin expression in different adipose tissue depots in therat

Serum leptin levels and leptin mRNA expression by adipose tissue increase w ith age and are mainly associated with an increase in adiposity. Regional c hanges in both leptin production and fat distribution contribute to circula ting leptin levels and may play a role in the regulation of body weight, a capacity that changes during development. Here, we have studied leptin mRNA expression in four different white adipose tissue depots (epididymal, retr operitoneal, mesenteric, inguinal; namely, EWAT, RWAT, MWAT, IWAT) and in i nterscapular brown adipose tissue (IBAT). We have also studied their relati onship with lipid content and adiposity changes, together with serum leptin levels in male rats at different ages (18, 55, 93, 159, 212, 294 and 355 d ays). Serum leptin levels increased during development, reaching st-able le vels at the age of 7 months, and, as expected, were highly correlated with both the adiposity index (r=0.908, P <0.01) and body weight (r=0.906, P<0.0 1). Leptin mRNA expression also increased with age, following characteristi c ontogenic patterns in every adipose tissue depot. The patterns were simil ar in EWAT and RWAT: leptin expression increased very rapidly during the fi rst 55 days for EWAT and 3 months for RWAT, with a peak in the latter at 7 months, and high expression levels were retained for the rest of the study period. In IWAT and IBAT, leptin expression increased steadily during the 1 2-month period studied and was significantly lower than levels in EWAT and RWAT. Leptin expression in MWAT increased progressively with age to reach l evels close to those of EWAT and RWAT in 10-month-old animals. The pattern of leptin expression in both EWAT and RWAT paralleled their lipid content, and leptin mRNA expression per unit of tissue lipid content was maintained high and constant from a very young age (about 2 and 3 months, respectively ). However, the expression of mRNA for leptin (expressed per unit of tissue lipid concentration) in MWAT, IWAT and IBAT increased steadily during the whole period studied, without attaining the maximal levels observed in EWAT and RWAT. MWAT, IWAT and IBAT maintained their capacity to increase leptin mRNA expression in response to at? additional accumulation of lipids. Our data demonstrate that there are regional-specific differences and different rates of increase of leptin gene expression within distinct depots of WAT and BAT. These changes cannot be uniquely explained by changes in adiposity or lipid content, implying that there are regional-specific regulatory mec hanisms that may depend on the attenuation with age of the <beta>-adrenergi c inhibitory signalling pathway upon leptin expression or on other factors.