Effect of High Glucose Levels on White Adipose Cells and Adipokines-Fuel for the Fire.

Alexander Sorisky

doi:10.3390/ijms18050944

Abstract

White adipocytes release adipokines that influence metabolic and vascular health. Hypertrophic obesity is associated with adipose tissue malfunctioning, leading to inflammation and insulin resistance. When pancreatic islet β cells can no longer compensate, the blood glucose concentration rises (hyperglycemia), resulting in type 2 diabetes. Hyperglycaemia may further aggravate adipose cell dysfunction in ~90% of patients with type 2 diabetes who are obese or overweight. This review will focus on the effects of high glucose levels on human adipose cells and the regulation of adipokines.

Highlights

The mature white adipocyte is distinguished morphologically by the large lipid droplet that occupies most of its interior space
The recent recognition of brown/beige adipose tissue in humans has stimulated new avenues of investigation to determine its role in human physiology and pathophysiology, but this topic is beyond the scope of this review
Dentelli et al reported that visceral preadipocytes isolated from patients with type 2 diabetes were more numerous than those from control subjects, and that they exist in a more de-differentiated versus a committed state, based on a higher expression of Oct4 and Nanog [19]

Summary

Introduction

The mature white adipocyte is distinguished morphologically by the large lipid droplet that occupies most of its interior space. Adipocytes are recognized for the myriad of adipokines (cytokines) they produce and release These bioactive factors have far-ranging effects on many physiological systems including appetite, energy expenditure, insulin sensitivity, inflammation, and coagulation. The widespread effects include increases in BiP/GRP78, calnexin, protein disulfide isomerase, X-BP1, as well as an increase in the phosphorylation of eIF2α, that increases ATF-4 protein and its action on target genes CCAAT/enhancer-binding protein homologous protein (CHOP) and ER oxidoreductin This induces inflammation and insulin resistance e.g., via JNK activation by IRE-1α, and via activation of the inhibitor of IκB kinase (IKK)β-nuclear factor (NF) κB pathway to up-regulate adipokine expression and release e.g., tumour necrosis factor (TNF)α, interleukin (IL)-6, and C-C motif chemokine ligand 2 (CCL2; known as monocyte chemotactic protein 1). Most of these studies used an elevated value of 15–25 mM glucose (some with dose-response studies) in comparison to a normal glucose concentration of 5 mM

High Glucose Levels and Preadipocyte Responses

High Glucose Levels and Adipocyte Differentiation