A specific immunoassay of uncoupling protein (UCP) and measurement of GDP binding were used to study the chronic responses of brown adipose tissue (BAT) mitochondria from rats made obese by dietary means (cafeteria rats)-and from obese rats subsequently fed a standard diet (post-cafeteria rats). We studied the response to fasting in order to assess the masking/unmasking responses in these groups. These studies have shown the following. (1) In the obese rats (cafeteria and post-cafeteria) the chronic increase in mitochondrial-UCP concentration compared with controls parallels the increase in GDP binding. (2) In 24 h-fasted control rats the decrease in GDP binding is associated with a change in UCP concentration, but in fasting cafeteria and post-cafeteria obese rats the decrease in GDP binding is not associated with any change in UCP concentration. (3) Post-cafeteria obese rats showed increased GDP binding and higher UCP concentrations than the controls, but these values were less than in cafeteria obese rats. (4) Control rats at 8 months old showed greater GDP binding and had a higher UCP concentration than 11-month-old control rats. (5) The responses of GDP binding and UCP concentration to fasting in post-cafeteria obese rats were similar to those in cafeteria obese rats, suggesting that such abbreviations are related to the obese status itself rather than to the composition of the cafeteria diet. The evidence supports the hypothesis that the response of the cafeteria and post-cafeteria obese rats to fasting is associated with a masking of UCP, whereas with chronic manipulation of diet changes in UCP concentration predominate. INTRODUCTIONBrown adipose tissue (BAT) is now viewed as a major site of both non-shivering and diet-induced thermogenesis in small mammals (for reviews see Shrago & Strieleman, 1987; HimmsHagen, 1989). The capacity for heat production in BAT is attributed to the loosely coupled respiration that can occur via the proton conductance pathway in mitochondria. Protons (or OH-) can pass through the BAT mitochondrial inner membrane via uncoupling protein (UCP), thus bypassing ATP synthesis (for reviews see Nicholls & Locke, 1984;Nicholls et al. 1986). All BAT mitochondria contain UCP (also known as thermogenin), which is a tissue-specific protein (M, 32000) that acts as a 'proton short-circuit', controlling the permeability of the inner membrane to protons. UCP is thus the principal factor regulating the uncoupling of respiration within the brown adipocyte (Nicholls & Locke, 1984).UCP has a high affinity for the binding of purine nucleotides (Heaton et al., 1978), and the binding of [3H]GDP to BAT mitochondria is frequently used as an indicator of thermogenic activity. Whether GDP binding is in fact a direct measure of the UCP content of the mitochondria has been the subject of several conflicting reports. Some studies suggest that the ability of UCP to bind GDP can change rapidly in response to acute cold exposure, noradrenaline and pharmacological agents or dietary manipulations (Desautels et ...

Sexual dimorphism has been found in mitochondrial features of skeletal muscle, with female rats showing greater mitochondrial mass and function compared with males. Adiponectin is an insulin-sensitizing adipokine whose expression has been related to mitochondrial function and that is also expressed in skeletal muscle, where it exerts local metabolic effects. The aim of this research was to elucidate the role of sex hormones in modulation of mitochondrial function, as well as its relationship with adiponectin production in rat skeletal muscle. An in vivo study with ovariectomized Wistar rats receiving or not receiving 17b-estradiol (E 2 ) (10 mg/kg per 48 h for 4 weeks) was carried out, in parallel with an assay of cultured myotubes (L6E9) treated with E 2 (10 nM), progesterone (Pg; 1 mM), or testosterone (1 mM). E 2 upregulated the markers of mitochondrial biogenesis and dynamics, and also of mitochondrial function in skeletal muscle and L6E9. Although in vivo E 2 supplementation only partially restored the decreased adiponectin expression levels induced by ovariectomy, these were enhanced by E 2 and Pg treatment in cultured myotubes, whereas testosterone showed no effects. Adiponectin receptor 1 expression was increased by E 2 treatment, both in vivo and in vitro, but testosterone decreased it. In conclusion, our results are in agreement with the sexual dimorphism previously reported in skeletal muscle mitochondrial function and indicate E 2 to be its main effector, as it enhances mitochondrial function and diminishes oxidative stress. Moreover, our data support the idea of the existence of a link between mitochondrial function and adiponectin expression in skeletal muscle, which could be modulated by sex hormones.

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