The intake of a high-fat diet triggers higher brown adipose tissue UCP1 levels in male rats but not in females

Abstract

UCP1 is a thermogenic uncoupling protein which is only expressed in the interscapular brown adipose tissue (BAT) (reviewed in [1]). Its expression is strongly induced by cold exposure, revealing the importance of this uncoupling protein in thermoregulation. Moreover, UCP1 expression is modulated by diet and metabolic hormones such as leptin and glucocorticoids, which suggests that UCP1 is involved in energy balance regulation. Leptin is an hormone mainly produced in white adipose tissue (WAT) that plays an important role in the central regulation of energy balance, inhibiting food intake and increasing energy expenditure (reviewed in [2]). The objective of this work is to study the effect of the intake of a high-fat (HF) diet for a prolonged period on BAT thermogenic potential and its relation with leptin signaling in both male and female rats. Male and female Wistar rats were fed after weaning and until day 180 of life with a normal-fat (NF) or a high-fat diet (HF) (10 or 45% calories from fat, respectively). After killing the animals, the inguinal and retroperitoneal WAT depots and the interscapular BAT were rapidly removed, frozen in liquid nitrogen and stored at −70°C until RNA analysis. Serum leptin levels, leptin expression in WAT, and UCP1 in BAT were determined (by ELISA, northern blot and western blot, respectively) on day 180 of life. Results show that animals fed with a HF diet for 6 months attained an overweight respect to controls that was more evident in females than in males (10.6 vs. 6.92%). Serum leptin levels (Fig. 1), but not WAT leptin expression (Table 1), were higher in HF diet fed animals, being the increase higher in females (76.1%) than in males (24.4%). On the other hand, HF diet intake resulted in higher BAT UCP1 levels in males, but not in females (Fig. 2). Fig. 1 Serum leptin levels in male and female rats measured by ELISA. Results are expressed as percentage in relation to serum leptin levels in NF rats Table 1 Leptin mRNA levels, measured by real-time PCR in male and female rats. Results are expressed as percentage in relation to the leptin expression in NF rats Fig. 2 BAT UCP1 levels in male and female rats. UCP1 levels were measured by Western Blot. Results are expressed as percentage in relation to the weight of NF rats. Asterisk effect of HF diet versus NF diet (P < 0.05, Student’s ... In conclusion, the intake of a HF diet for a prolonged period seems to impair central regulation of leptin-dependent diet induced thermogenesis in female rats, which could partially explain the higher weight gain of female versus male rats under HF diet. Key words: uncoupling protein 1, thermogenesis, high-fat diet, leptin.