Sex-dependent Thermogenesis, Differences in Mitochondrial Morphology and Function, and Adrenergic Response in Brown Adipose Tissue

Abstract

Gender-related differences in brown adipose tissue (BAT) thermogenesis of 110-day-old rats were studied by determining the morphological and functional features of BAT. The adrenergic control was assessed by studying the levels of ␤ 3 -and ␣ 2A -adrenergic receptors (AR) and by determining the lipolytic response to norepinephrine (␤ 1 -, ␤ 2 -, ␤ 3 -, and ␣ 2 -AR agonist), isoprenaline (␤ 1 -, ␤ 2 -, and ␤ 3 -AR agonist), and CGP12177A (selective partial ␤ 3 -AR agonist but ␤ 1 -and ␤ 2 -AR antagonist) together with post-receptor agents, forskolin and dibutyryl cyclic AMP. The female rats that had greater oxygen consumption showed higher UCP1 content, a higher multilocular arrangement, and both longer cristae and higher cristae dense mitochondria in BAT indicating heightened thermogenic capacity and activity; this picture is accompanied by a more sensitive ␤ 3 -AR to norepinephrine signal (EC 50 10-fold lower for CGP12177A) and a lower expression of ␣ 2A -AR than male rats. Taken together, our results support the idea that the BAT hormonal environment could be involved in the control of different elements of lipolytic and thermogenic adrenergic pathways. Gender dimorphism is both at receptor (changing ␣ 2A -AR density and ␤ 3 -AR affinity) and post-receptor (modulating the links involved in the adrenergic signal transduction) levels. These changes in adrenergic control could be responsible, at least in part, both for the important mitochondrial recruitment differences and functional and morphological features of BAT in female rats under usual rodent housing temperatures.

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

“…Ucp1 expression in adipocytes can be sex dependent as previously shown for rat BAT42 and in differentiated stem cells from human perirenal adipose tissue 43. We also observed a tendency for higher Ucp1 expression levels in GLY‐injected TA muscles from female compared with male Sv/129 mice in vivo ( Figure 1B).…”

Sexual dimorphism in liver mitochondrial oxidative capacity is conserved under caloric restriction conditions

“…Liver samples (5 g) were homogenized in 35 ml of ice-cold isolation buffer with a Teflon/glass homogenizer. Aliquots were stored at Ϫ80°C for determination of total DNA (46), triglycerides (43), and protein content (5). The rest of the homogenate was used for isolation of mitochondria by differential centrifugation.…”

Role of sex hormones in modulation of brown adipose tissue activity

“…Some differences in BAT thermogenic capacity, detected between males and females in response to diet-induced obesity and cold exposure (Quevedo et al 1998, Roca et al 1999, Rodriguez et al 2001, Rodriguez-Cuenca et al 2002, seem to point to a role played by sex hormones in the control of BAT activity. These gender differences are probably due to a dimorphism in mitochondrial capacity; indeed, female BAT shows larger mitochondria and higher cristae density compared with the BAT present in males (Rodriguez-Cuenca et al 2002).…”

“…These gender differences are probably due to a dimorphism in mitochondrial capacity; indeed, female BAT shows larger mitochondria and higher cristae density compared with the BAT present in males (Rodriguez-Cuenca et al 2002). An augmented thermogenic activity, driven by the increased mitochondrial function of female BAT, may underlie the different body weight gain that female rodents exhibit following a high-fat diet (HFD) in comparison with males.…”