Sex-dependent dietary obesity, induction of UCPs, and leptin expression in rat adipose tissues.

OBJECTIVE: The aim of this study was to determine the sex-dependent differences in the response of key parameters involved in thermogenesis and control of body weight in brown adipose tissue (BAT) and white adipose tissue (WAT) in postcafeteria-fed rats, a model of dietary obesity.

RESEARCH METHODS AND PROCEDURES: BAT and WAT were obtained from male and female control and postcafeteria-fed Wistar rats. Postcafeteria-fed rats were initially fed with cafeteria diet from day 10 of life until day 110 (cafeteria period) and with standard chow diet from then until day 180 of life (postcafeteria period). Body mass and energy intake were evaluated. Biometric parameters were analyzed in interscapular BAT (IBAT). Levels of uncoupling protein 1 (UCP1), alpha(2)-adrenergic receptor (AR), and beta(3)-AR proteins and UCP1, UCP2, UCP3, beta(3)-AR, and leptin mRNAs, in IBAT or WAT, were studied by Western blot and Northern blot analyses, respectively.

RESULTS: Rats attained 59% (females) and 39% (males) increase in body weight at the end of the cafeteria period. During the postcafeteria period, the rats showed a loss of body weight, which was higher in females. Postcafeteria-fed female rats also presented higher activation of thermogenic parameters in IBAT, including UCP1, UCP2, and UCP3 mRNAs. Female control rats showed lower levels of both alpha 2 and beta(3)-ARs in BAT compared with male rats, but these levels in postcafeteria-fed female and male rats were the same, because males tended to down-regulate them. Levels of leptin mRNA in response to the postcafeteria state depended on gender and the specific WAT depot studied.

DISCUSSION: It is suggested that in postcafeteria-fed female rats, BAT thermogenic capacity becomes more efficiently activated than in males. Female rats also showed a bigger weight loss. The parallel regulation of the levels of UCP2 and UCP3 mRNAs, with respect to UCP1 mRNA, with higher activation in female postcafeteria-fed rats, suggests a possible role of both UCP2 and UCP3 in the regulation of energy expenditure and in the control of body weight. The distinct responses to overweight of alpha 2 and beta(3)-ARs--which were sex dependent--and leptin mRNA--which depended on both sex and WAT depot--also support the different response of thermogenesis-related parameters between overweight males and females.