Mechanisms of insulin resistance related to white, beige, and brown adipocytes

Background: The diminished glucose lowering effect of insulin in obesity, called “insulin resistance,” is associated with glucose intolerance, type 2 diabetes, and other serious maladies. Many publications on this topic have suggested numerous hypotheses on the molecular and cellular disruptions tha...

Full description

Bibliographic Details
Main Author: Michael P. Czech
Format: Article
Language:English
Published: Elsevier 2020-04-01
Series:Molecular Metabolism
Online Access:http://www.sciencedirect.com/science/article/pii/S2212877819309664
id doaj-7285670ef27449178d19d995ed4e7201
record_format Article
spelling doaj-7285670ef27449178d19d995ed4e72012020-11-25T03:10:05ZengElsevierMolecular Metabolism2212-87782020-04-01342742Mechanisms of insulin resistance related to white, beige, and brown adipocytesMichael P. Czech0Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USABackground: The diminished glucose lowering effect of insulin in obesity, called “insulin resistance,” is associated with glucose intolerance, type 2 diabetes, and other serious maladies. Many publications on this topic have suggested numerous hypotheses on the molecular and cellular disruptions that contribute to the syndrome. However, significant uncertainty remains on the mechanisms of its initiation and long-term maintenance. Scope of review: To simplify insulin resistance analysis, this review focuses on the unifying concept that adipose tissue is a central regulator of systemic glucose homeostasis by controlling liver and skeletal muscle metabolism. Key aspects of adipose function related to insulin resistance reviewed are: 1) the modes by which specific adipose tissues control hepatic glucose output and systemic glucose disposal, 2) recently acquired understanding of the underlying mechanisms of these modes of regulation, and 3) the steps in these pathways adversely affected by obesity that cause insulin resistance. Major conclusions: Adipocyte heterogeneity is required to mediate the multiple pathways that control systemic glucose tolerance. White adipocytes specialize in sequestering triglycerides away from the liver, muscle, and other tissues to limit toxicity. In contrast, brown/beige adipocytes are very active in directly taking up glucose in response to β adrenergic signaling and insulin and enhancing energy expenditure. Nonetheless, white, beige, and brown adipocytes all share the common feature of secreting factors and possibly exosomes that act on distant tissues to control glucose homeostasis. Obesity exerts deleterious effects on each of these adipocyte functions to cause insulin resistance. Keywords: Adipokines, Adipose tissues, Adrenergic receptors, Bioactive lipids, Glucose tolerance, Lipogenesis, Signaling, Thermogenesis, Uncoupling proteinhttp://www.sciencedirect.com/science/article/pii/S2212877819309664
collection DOAJ
language English
format Article
sources DOAJ
author Michael P. Czech
spellingShingle Michael P. Czech
Mechanisms of insulin resistance related to white, beige, and brown adipocytes
Molecular Metabolism
author_facet Michael P. Czech
author_sort Michael P. Czech
title Mechanisms of insulin resistance related to white, beige, and brown adipocytes
title_short Mechanisms of insulin resistance related to white, beige, and brown adipocytes
title_full Mechanisms of insulin resistance related to white, beige, and brown adipocytes
title_fullStr Mechanisms of insulin resistance related to white, beige, and brown adipocytes
title_full_unstemmed Mechanisms of insulin resistance related to white, beige, and brown adipocytes
title_sort mechanisms of insulin resistance related to white, beige, and brown adipocytes
publisher Elsevier
series Molecular Metabolism
issn 2212-8778
publishDate 2020-04-01
description Background: The diminished glucose lowering effect of insulin in obesity, called “insulin resistance,” is associated with glucose intolerance, type 2 diabetes, and other serious maladies. Many publications on this topic have suggested numerous hypotheses on the molecular and cellular disruptions that contribute to the syndrome. However, significant uncertainty remains on the mechanisms of its initiation and long-term maintenance. Scope of review: To simplify insulin resistance analysis, this review focuses on the unifying concept that adipose tissue is a central regulator of systemic glucose homeostasis by controlling liver and skeletal muscle metabolism. Key aspects of adipose function related to insulin resistance reviewed are: 1) the modes by which specific adipose tissues control hepatic glucose output and systemic glucose disposal, 2) recently acquired understanding of the underlying mechanisms of these modes of regulation, and 3) the steps in these pathways adversely affected by obesity that cause insulin resistance. Major conclusions: Adipocyte heterogeneity is required to mediate the multiple pathways that control systemic glucose tolerance. White adipocytes specialize in sequestering triglycerides away from the liver, muscle, and other tissues to limit toxicity. In contrast, brown/beige adipocytes are very active in directly taking up glucose in response to β adrenergic signaling and insulin and enhancing energy expenditure. Nonetheless, white, beige, and brown adipocytes all share the common feature of secreting factors and possibly exosomes that act on distant tissues to control glucose homeostasis. Obesity exerts deleterious effects on each of these adipocyte functions to cause insulin resistance. Keywords: Adipokines, Adipose tissues, Adrenergic receptors, Bioactive lipids, Glucose tolerance, Lipogenesis, Signaling, Thermogenesis, Uncoupling protein
url http://www.sciencedirect.com/science/article/pii/S2212877819309664
work_keys_str_mv AT michaelpczech mechanismsofinsulinresistancerelatedtowhitebeigeandbrownadipocytes
_version_ 1724660692603109376