Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion

Abstract

Summary Glucose homeostasis is maintained through organ crosstalk that regulates secretion of insulin to keep blood glucose levels within a physiological range. In type 2 diabetes, this coordinated response is altered, leading to a deregulation of beta cell function and inadequate insulin secretion. Reprogramming of white adipose tissue has a central role in this deregulation, but the critical regulatory components remain unclear. Here, we demonstrate that expression of the transcriptional coregulator GPS2 in white adipose tissue is correlated with insulin secretion rate in humans. The causality of this relationship is confirmed using adipocyte-specific GPS2 knockout mice, in which inappropriate secretion of insulin promotes glucose intolerance. This phenotype is driven by adipose-tissue-secreted factors, which cause increased pancreatic islet inflammation and impaired beta cell function. Thus, our study suggests that, in mice and in humans, GPS2 controls the reprogramming of white adipocytes to influence pancreatic islet function and insulin secretion.

Identification of key genes affecting porcine fat deposition based on co-expression network analysis of weighted genes

“…The decrease in GPS2 expression in adipocytes is closely associated with obesity [ 41 , 42 ]. A previous study suggested that, in mice and humans, GPS2 controls the reprogramming of white adipocytes, influencing pancreatic islet function and insulin secretion, thus affecting fat deposition [ 43 ]. In the blue module, TCAP exists in three significantly enriched terms: myofibril (GO:0030016), I band (GO:0031674), and sarcomere (GO:0030017).…”

Role of the Gut Microbiome in Beta Cell and Adipose Tissue Crosstalk: A Review

“…Specific adipose tissue proteomic and transcriptomic profiles associated with inflammatory pathways may also be involved in beta cell dysfunction ( 51 ). Recently, the transcriptional coregulator GPS2 in white adipose tissue has been associated with beta cell insulin secretion ( 52 ).…”

Transcriptional and epigenetic control of adipocyte remodeling during obesity

“…Not surprisingly, their dysregulated production or secretion is implicated in metabolic and inflammatory diseases (21). We recently demonstrated that the transcriptional reprogramming of adipose tissue during energy surplus leads to the production of adipokines that influence adipose tissue remodeling and pancreatic islet function (insulin secretion) in the context of obesity and type 2 diabetes (22).…”

“…Future studies are still necessary to dissect the relationship between the environment and the possible inheritance of altered adipocyte functionality and plasticity. Closely linked epigenome and transcriptome alterations that originate in different adipocyte subtypes/subpopulations (45), likely along with related alterations in adjacent immune cells including macrophages (111), may affect other aspects to be scrutinized, such as interorgan cross talk to pancreatic islets (22) and liver.…”