The role of glucose-6-phosphate dehydrogenase in adipose tissue inflammation in obesity

Abstract

Obesity is closely associated with metabolic diseases including type 2 diabetes. One hallmark characteristics of obesity is chronic inflammation that is coordinately controlled by complex signaling networks in adipose tissues. Compelling evidence indicates that reactive oxygen species (ROS) and its related signaling pathways play crucial roles in the progression of chronic inflammation in obesity. The pentose phosphate pathway (PPP) is an anabolic pathway that utilizes the glucoses to generate molecular building blocks and reducing equivalents in the form of NADPH. In particular, NADPH acts as one of the key modulators in the control of ROS through providing an electron for both ROS generation and scavenging. Recently, we have reported that glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the PPP, is implicated in adipose tissue inflammation and systemic insulin resistance in obesity. Mechanistically, G6PD potentiates generation of ROS that augments pro-inflammatory responses in adipose tissue macrophages, leading to systemic insulin resistance. Here, we provide an overview of cell type-specific roles of G6PD in the regulation of ROS balance as well as additional details on the significance of G6PD that contributes to pro-oxidant NADPH generation in obesity-related chronic inflammation and insulin resistance.

Antioxidant SMe1EC2 modulates pentose phosphate pathway and glutathione-dependent enzyme activities in tissues of aged diabetic rats

“…NADPH oxidases generally act as pro-oxidant enzymes, playing a crucial role in the pathogenesis of diabetes complications and the aging process. In our study, diabetes in aged rats led to a decrease in G6PDH, 6PGDH and GST only in the liver and no other tissues studied that displayed increased or unchanged G6PDH, 6PGDH or GST, suggesting the cell type-specific roles of PPP in the regulation of ROS balance, as indicated before (Park et al , 2017 ). The decline in liver G6PDH, 6PGDH and GST may be due to excessive oxidative stress as indicated previously, showing that different types of tissue increase the utilization of G6PDH and 6PGDH under oxidative stress conditions to allow efficient regeneration of NADPH and the reduction of glutathione disulfide (GSSG) to GSH via GR, which enhances the antioxidant defense system (Bolaños and Almeida, 2010 ).…”

Stachys sieboldii Miq. Root Attenuates Weight Gain and Dyslipidemia in Rats on a High-Fat and High-Cholesterol Diet

“…In addition, we hypothesized that SS supplementation could change lipid metabolism at the transcriptional level. Increased mRNA levels of G6pdh, a rate-limiting enzyme of the pentose phosphate pathway (PPP), are reportedly associated with adipose tissue inflammation [ 51 ]. As commonly seen in obesity, the hepatic G6pdh mRNA expression was significantly increased following the HFC diet ( Figure 9 C–F).…”

Cooperative and Independent Functions of the miR-23a~27a~24-2 Cluster in Bovine Adipocyte Adipogenesis

“…G6PD is a rate-limiting enzyme in the pentose phosphate pathway and is indispensable in de novo lipogenesis [24]. It has also been implicated in adipose tissue inflammation and systemic insulin resistance in obesity [27]. It was recently demonstrated that abnormal activation of G6PD increases cellular nicotinamide adenine dinucleotide phosphate (NADPH), resulting in lipid dysregulation in obesity [47].…”

“…In the process of preadipocyte differentiation, fatty acids, and lipid synthesis pathways, such as oxidative phosphorylation, pentose phosphate pathway, and triacylglycerol (TAG) synthesis pathway, play essential roles [24,25,26]. In these cellular bioprocesses, adenosine triphosphate synthase peripheral stalk-membrane subunit b (ATP5F1) is important for oxidative phosphorylation [25], G6PD is essential for pentose phosphate pathway [27], and GPAM, DGAT2, DCN, and LPL are the key regulators for TAG synthesis [28,29,30]. Although it is much clearer how these genes affect adipogenesis, the interactions between these pathways and miRNA networks are largely unknown.…”