SPLTRAK Abstract Submission
Activation of brown adipose tissue thermogenesis in response to high-fat/sugar choice diet challenge is dictated by sex. 
1Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden/2Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
   Women and men have different patterns of illness and they respond differently to pharmacotherapies. Obesity is more prevalent in women compared to men, and women are more likely to develop morbid obesity, according to NIDDK. Preclinical studies designed to not only determine whether there are sex differences in commonly used rat models of obesity, but also aiming to pursue the identified differences mechanistically are still lacking. Therefore, the main aim of this study was to 1) determine whether time course and presentation of diet-induced obesity differs between male and female rats, and 2) investigate the mechanisms underlying potential differences. To achieve this, male and female rats were offered a choice of a high-fat/high-sugar (HFHS) diet and regular chow for 12 weeks. Body weight gain, food intake, fat mass, and brown adipose tissue thermogenesis were measured. The extent of overconsumption was similar in males and females offered a choice of HFHS and chow, compared to control rats offered only chow; the impact of that overconsumption on weight gain and blood sugar differed significantly. While females started gaining weight immediately, males were protected from weight gain until 10 weeks on the diet, suggesting that males were able to engage compensatory energy expenditure strategy. In line with this idea, we found that HFHS-fed males, but not females, displayed a clear and potent diet induced thermogenesis driven by activation of brown adipose tissue. We are now pursuing the molecular mechanisms of this sex divergent response to HFHS diet challenge, including potential differences in sympathetic activation of brown adipose tissue and ability to engage white fat browning. These data may also suggest that sex specific weigh loss therapies should be considered.

Supported By: the Swedish Research Council, the Novo Nordisk Foundation Excellence project grant, the Ragnar Söderberg Foundation, Harald Jeanssons Stiftelse and Greta Jeanssons Stiftelse, Magnus Bergvalls Stiftelse, the Wallenberg Foundation and the Center for Molecular and Translational Medicine