Long-term hypercortisolism induces lipogenesis promoting palmitic acid accumulation and inflammation in visceral adipose tissue compared to HFD-induced obesity.

Glucocorticoids (GCs) play critical roles in adipose tissue metabolism. Here, we compare in a mouse model the effects of chronic glucocorticoid excess and diet-induced obesity in the white adipose tissue mass and distribution, by focusing on the visceral adipose tissue fatty acid composition changes, the role of de novo lipogenesis (DNL) and the inflammatory state. We used a non-invasive mouse model of hypercortisolism to compare GCs-induced effects on adipose tissue with diet-induced obesity (HFD 45%) and control mice after ten weeks of treatment. Subcutaneous (SAT) and visceral adipose tissue (VAT) mass and distribution were measured by nuclear magnetic resonance imaging (NMRI). Fatty acids composition in VAT was analyzed by NMR spectroscopy and gas chromatography. Gene expression of key enzymes involved in DNL were analyzed in liver and VAT. Macrophage infiltration markers and pro-inflammatory cytokines were measured by gene expression in VAT. HFD or GCs treatment induced similar fat mass expansion with comparable distribution between SAT and VAT depots. However, in VAT, GCs induces DNL, higher palmitic acid (PA), macrophage infiltration and pro-inflammatory cytokines levels, accompanied by systemic NEFA elevation, hyperinsulinemia and higher HOMA-IR levels compared to diet-induced obesity. Thus, chronic hypercortisolism induces DNL and modify fatty acids composition towards increased SFA reduced PUFA levels in VAT, promoting macrophage recruitment and pro-inflammatory cytokines suggesting a worse cardiometabolic profile even compared to HFD mice.