Endocrine Abstracts

JOINT457

Background: Diet-induced obesity is an escalating health issue. Women have a higher prevalence of obesity than men, yet reproductive-age women have a lower incidence of metabolic diseases, including type 2 diabetes. This sex difference attenuates after menopause, suggesting protective roles of female sex hormones. However, the mechanisms by which sex hormones and high-fat, high-sucrose diet (HFD) influence white adipose tissue (WAT) adaptation, including adipokine secretion, remain to be explored.

Methods: Fifty-six C57BL/6NJcl mice [28 males (M) and 28 females (F)] were studied, with 14 per sex undergoing gonadectomy (G) and the rest receiving a sham operation (S) at 8 weeks old. After a one-week recovery, 7 mice from each group were switched to HFD for 12 weeks, while others remained on a standard chow diet (CD), resulting in 8 groups: MSC, MGC, FSC, FGC, MSH, MGH, FSH, and FGH. An intraperitoneal glucose tolerance test (IPGTT) was performed at 21 weeks old. At 22 weeks old, WAT was collected and underwent ex vivo insulin stimulation to assess Akt phosphorylation by Western blotting.

Results: HFD increased body weight (BW) in all groups (P < 0. 01). Despite similar dietary calorie intake in HFD-fed groups, FSH had the least BW gain (P < 0. 01). Fasting glucose levels were higher in males than females and were increased by HFD and gonadectomy (all P < 0. 01). Fasting insulin levels, as well as the HOMA-IR, were significantly elevated by HFD feeding in most groups (P < 0. 01), except sham-operated females (FSC vs. FSH, p>0. 90). IPGTT confirmed that HFD induced glucose intolerance (P < 0. 01), though FSH showed better glucose tolerance than other HFD-fed groups. WAT weight increased with HFD (P < 0. 01), being higher in males and gonadectomized mice (both P < 0. 01). Serum leptin levels mirrored WAT mass, increasing with HFD (P < 0. 01), being higher in males (P = 0. 02), and elevated by gonadectomy (P < 0. 01). Serum adiponectin levels showed a sex-specific pattern, increasing with HFD only in gonad-intact females (FSH>FSC, P = 0. 02; FSH>MSH, P = 0. 02), resulting in the highest adiponectin/leptin ratio among HFD-fed groups. Insulin-stimulated Akt phosphorylation in WAT explants was reduced in HFD-fed groups (P < 0. 01), with a greater reduction in males (P < 0. 01) than females (P = 0. 09).

Conclusion: HFD impairs glucose homeostasis and insulin signaling in a sex-dependent manner. Gonad-intact females exhibit better metabolic adaptation under HFD, reflected by lower BW gain, better glucose tolerance, a higher adiponectin/leptin ratio, and a smaller reduction in Akt phosphorylation in WAT. These findings highlight the protective role of female gonadal hormones in metabolic adaptation to diet-induced obesity.