Elevated Steroid Hormone Production in the db/db Mouse Model of Obesity and Type 2 Diabetes

Abstract

Obesity and type 2 diabetes have become a major public health problem worldwide. Steroid hormone dysfunction appears to be linked to development of obesity and type 2 diabetes and correction of steroid abnormalities may offer new approaches to therapy. We therefore analyzed plasma steroids in 15-16 week old obese and diabetic <i>db/db</i> mice using liquid chromatography-tandem mass spectrometry. Lean <i>db/+</i> served as controls. <i>Db/db</i> mice developed obesity, hyperglycemia, hyperleptinemia, and hyperlipidemia. Hepatic triglyceride storage was increased and adiponectin and pancreatic insulin were lowered. Aldosterone, corticosterone, 11-deoxycorticosterone, and progesterone were respectively increased by 3.6-, 2.9-, 3.4, and 1.7-fold in <i>db/db</i> mice compared to controls. Ratios of aldosterone-to-progesterone and corticosterone-to-progesterone were respectively 2.0- and 1.5-fold higher in <i>db/db</i> mice. Genes associated with steroidogenesis were quantified in the adrenal glands and gonadal adipose tissues. In adrenals, <i>Cyp11b2</i>, <i>Cyp11b1</i>, <i>Cyp21a1</i>, <i>Hsd3b1</i>, <i>Cyp11a1</i>, and <i>StAR</i> were all significantly increased in <i>db/db</i> mice compared with <i>db/+</i> controls. In adipose tissue, no <i>Cyp11b2</i> or <i>Cyp11b1</i> transcripts were detected and no differences in <i>Cyp21a1</i>, <i>Hsd3b1</i>, <i>Cyp11a1</i>, or <i>StAR</i> expression were found between <i>db/+</i> and <i>db/db</i> mice. In conclusion, the present study showed an elevated steroid hormone production and adrenal steroidogenesis in the <i>db/db</i> model of obesity and type 2 diabetes.