Altered glucose and lipid metabolism in transgenic female mice with hypersecretion of human chorionic gonadotropin (hCG)

STEVENS G, RATNER LD, POUTANEN M, HUHTANIEMI IT, CALANDRA RS, RULLI SB.

San Francisco

Congreso; The Endocrine Society´s 95 th Annual Meeting; 2013

The Endocrine Society

Metabolic syndrome is a growing epidemic; it increases the risk for diabetes, cardiovascular disease, fatty liver and several cancers. Women with hyperandrogenic conditions present with central obesity in over 50% of cases and insulin resistance in 50-70%. Transgenic female mice overexpressing the human chorionic gonadotropin b and a/b-subunit (hCGb+ and hCGab+ mice) are obese, have constitutively elevated levels of hCG and increased production of testosterone, progesterone and prolactin (1). The objective of this study was to investigate possible alterations of the glucose and lipid metabolism in adult hCGb+ and hCGab+ females, and the influence of gonadal steroids in this process. We evaluated fasting levels of serum of triglycerides, cholesterol, HDL-C, glucose and insulin in wild-type (WT) and transgenic females at 6 months of age. Glucose and insulin response tests were also determined in these mice. Both adult hCGb+ and hCGab+ females showed increased body weight with accumulation of visceral adipose tissue, accompanied by hyperinsulinemia (WT: 0.14±0.07; hCGb+: 0.8±0.2 ng/ml, p 0.05 and hCGab+: 2.4±0.5 ng/ml, p 0.001), glucose intolerance and insulin resistance, as manifested by decreased response to insulin, increased HOMA (homeostatic model assessment, for assessing beta cell function and insulin resistance) and decreased QUICKI (quantitative insulin sensitivity check index) ratios. Lipid profile showed elevated triglyceride levels (WT: 134.9±11.7; hCGb+: 633.9±61.4 mg/dl and hCGab+: 851.4±91.2 mg/dl, p 0.01), conserved cholesterol and increased atherogenic indices (cholesterol/HDL-C and triglycerides/HDL-C) in transgenic females. On the other hand, ovariectomized hCGb+ females at 6 weeks of age (Ovx) exhibited increased glucose levels (WT: 131.8±3.3; hCGb+: 141.8±6.1, Ovx: 213.3±11.6 mg/dl p 0.05), lower triglyceride levels (hCGb+: 633.9±61.4, Ovx+: 189.96±24.1 mg/dl, p 0.001), recovered insulin sensitivity and reduced body weight. These results demonstrate that hCG overexpression together with hyperandrogenism and obesity in adult female mice are associated to hyperinsulinemia, insulin resistance and dyslipidemia, which were prevented by ovariectomy. These findings provide essential information for further studies on the involvement of gonadotropins and steroid hormones in metabolic disorders.