Long-term hypercortisolism induces lipogenesis promoting palmitic acid accumulation and inflammation in visceral adipose tissue compared with HFD-induced obesity
- 1 June 2020
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 318 (6), E995-E1003
- https://doi.org/10.1152/ajpendo.00516.2019
Abstract
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 on white adipose tissue mass and distribution, by focusing on visceral adipose tissue (VAT) fatty acid composition changes, the role of de novo lipogenesis (DNL) and the inflammatory state. We used a noninvasive mouse model of hypercortisolism to compare GC-induced effects on adipose tissue with diet-induced obesity [high-fat diet (HFD) 45%] and control mice after 10 wk of treatment. Subcutaneous adipose tissue (SAT) and VAT mass and distribution were measured by nuclear magnetic resonance imaging (NMRI). Fatty acid composition in VAT was analyzed by NMR spectroscopy and gas chromatography. Gene expression of key enzymes involved in DNL was analyzed in liver and VAT. Macrophage infiltration markers and proinflammatory cytokines were measured by gene expression in VAT. HFD or GC treatment induced similar fat mass expansion with comparable distribution between SAT and VAT depots. However, in VAT, GCs induce DNL., higher palmitic acid (PA), macrophage infiltration, and proinflammatory cytokine levels, accompanied by systemic nonesterified fatty acid (NEFA) elevation. hyperinsulinemia, and higher homeostatic model assessment for insulin resistance (HOMA-IR) levels compared with diet-induced obesity. Thus. chronic hypercortisolism induces DNI, and fatty acid composition changes toward increased SFA and reduced polyunsaturated fatty acid (PUPA) levels in VAT, promoting macrophage recruitment and proinflammatory cytokines, suggesting a worse cardiometabolic profile even compared with HFD mice.Funding Information
- Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (FIS PI_1500859, Miguel Servet fellowship (CP II 17/00029))
- Generalitat de Catalunya (FI-AGAUR (2016 FI_B00702))
This publication has 59 references indexed in Scilit:
- De novo lipogenesis in health and diseaseMetabolism, 2014
- Chronic glucocorticoid treatment enhances lipogenic activity in visceral adipocytes of male Wistar ratsActa Physiologica, 2014
- Glucocorticoid excess induces long-lasting changes in body composition in male C57Bl/6J mice only with high-fat dietPhysiological Reports, 2013
- In vivo imaging of lipid storage and regression in diet-induced obesity during nutrition manipulationAmerican Journal of Physiology-Endocrinology and Metabolism, 2012
- Different Adipose Depots: Their Role in the Development of Metabolic Syndrome and Mitochondrial Response to Hypolipidemic AgentsJournal of Obesity, 2011
- Dietary Fatty Acids Differentially Regulate Production of TNF‐α and IL‐10 by Murine 3T3‐L1 AdipocytesObesity, 2008
- ATP-Citrate Lyase Deficiency in the MouseOnline Journal of Public Health Informatics, 2004
- Effects of cortisol on lipolysis and regional interstitial glycerol levels in humansAmerican Journal of Physiology-Endocrinology and Metabolism, 2002
- A method for separation of phosphatidylcholine, triacylglycerol, non-esterified fatty acids and cholesterol esters from plasma by solid-phase extractionBritish Journal of Nutrition, 2000
- Visceral obesity and metabolic syndromeObesity Reviews, 2000