Chronic hyperinsulinemia promotes meta-inflammation and extracellular matrix deposition in adipose tissue: Implications of nitric oxide

Molecular and Cellular Endocrinology
Durgesh KumarAnil N Gaikwad

Abstract

Various imperative studies support the notion that hyperinsulinemia (HI) itself serves as the common link between adipose tissue inflammation (ATI) and metabolic syndrome. However, the contribution of HI mediated ATI and its metabolic consequences are yet to be explored. We induced chronic HI per se in mice by administration of exogenous insulin for 8 weeks through mini-osmotic pumps. For the reduction of circulating insulin in response to excess calorie intake, we have partially ablated β-cells by using streptozotocin (STZ) in the diet-induced obesity (DIO) and genetic mice models (db/db). Flow cytometry analysis was performed for the quantification of immune cells in stromal vascular fraction (SVF) isolated from epididymal white adipose tissue (eWAT). Our studies demonstrated that chronic HI augmented ATI in terms of elevated pro-inflammatory cells (M1 macrophages and NK-cells) and suppressed anti-inflammatory cells (M2 macrophages, eosinophils and regulatory T-cells). These results were correlated with altered obesity-associated metabolic phenotype. Partial reduction of circulating insulin level attenuated excess calorie-induced ATI and improved insulin sensitivity. Mechanistically, an imbalance in M1 and M2 macrophage propo...Continue Reading

Citations

Feb 5, 2019·Climacteric : the Journal of the International Menopause Society·P Chedraui, F R Pérez-López
Nov 7, 2019·Trends in Endocrinology and Metabolism : TEM·Zahra BahadoranAsghar Ghasemi
Mar 2, 2019·European Journal of Pharmacology·Kripa ShankarAnil Nilkanth Gaikwad
Mar 13, 2020·The Journal of Nutritional Biochemistry·Rachel M GolonkaMatam Vijay-Kumar
May 29, 2021·Reproductive Sciences·Nan-Xing Jiang, Xue-Lian Li
Mar 21, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Joseph W BealsSamuel Klein

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