Endocrine Abstracts

JOINT1049

Background: Overweight and obesity are escalating global health challenges, with food containing high fat and sugar being one of the causes. The discovery of functional brown adipose tissue (BAT), an organ of non-shivering thermogenesis, in adults offers new opportunities for obesity therapies. Emerging evidence suggests that sex hormones influence BAT structure and function, but the exact mechanisms remain to be fully elucidated.

Methods: Fifty-six mice [28 males (M), 28 females (F)] were used, with 14 per sex undergoing gonadectomy (G) at 8 weeks old, and the rest receiving a sham operation (S). After a one-week recovery, 7 mice from each group were switched to a high-fat, high-sucrose diet (HFD) for 12 weeks, while the others continued on standard chow diet (CD), resulting in a total of 8 groups: MSC, MGC, FSC, FGC, MSH, MGH, FSH, and FGH. At the end (age 22 weeks), interscapular BAT was collected. BAT morphology was analyzed using ImageJ with the Adiposoft extension. mRNA expression levels were quantified by qPCR.

Results: HFD increased BAT weight, reduced nuclear density, and increased droplet size in BAT across all groups. While Ucp1 expression (a thermogenic gene) showed no sex differences among CD-fed groups, HFD-fed females expressed more Ucp1 than males (FSH>MSH, P = 0.04). Gonadectomy influenced Ucp1 expression in a sex-dependent manner in the HFD-fed group, increasing it in males (MGH>MSH, P < 0.01) but having minimal effect in females. Ppargc1a, a transcriptional coactivator of Ucp1, and lipolytic genes Atgl and Hsl followed similar trends to Ucp1, showing little changes with HFD but significant alterations with gonadectomy in a sex-dependent fashion. For fatty acid uptake, Lpl expression was not significantly affected by HFD alone (P = 0.31) but was significantly reduced when combined with gonadectomy in both sexes (P < 0.01). HFD decreased Pck1 (a gluconeogenic gene) expression across all groups (P < 0.01). Additionally, HFD suppressed Cfd (adipsin, an anti-thermogenic adipokine) expression in all groups (P < 0.01), and gonadectomy reduced Cfd levels in females regardless of diet condition (P < 0.01).

Conclusion: HFD and sex hormones, along with their interaction, influence BAT morphology, metabolism, and substrate uptake. Gonadectomy shows a stronger effect than HFD on thermogenic and lipolytic activities. These findings reveal complex hormonal-dietary effects, providing insights into HFD-induced obesity and potential therapeutic strategies.