Glucose-6-phosphate dehydrogenase deficiency improves insulin resistance with reduced adipose tissue inflammation in obesity

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Title
Glucose-6-phosphate dehydrogenase deficiency improves insulin resistance with reduced adipose tissue inflammation in obesity
Author(s)
M Ham; S S Choe; K C Shin; G Choi; J W Kim; Jung Ran NohYong-Hoon Kim; J W Ryu; K H Yoon; Chul Ho Lee; Jae Bum Kim
Bibliographic Citation
Diabetes, vol. 65, no. 9, pp. 2624-2638
Publication Year
2016
Abstract
Glucose-6-phosphate dehydrogenase (G6PD), a ratelimiting enzyme of the pentose phosphate pathway, plays important roles in redox regulation and de novo lipogenesis. It was recently demonstrated that aberrant upregulation of G6PD in obese adipose tissue mediates insulin resistance as a result of imbalanced energy metabolism and oxidative stress. It remains elusive, however, whether inhibition of G6PD in vivo may relieve obesity-induced insulin resistance. In this study we showed that a hematopoietic G6PD defect alleviates insulin resistance in obesity, accompanied by reduced adipose tissue inflammation. Compared with wild-type littermates, G6PD-deficient mutant (G6PDmut) mice were glucose tolerant upon high-fat-diet (HFD) feeding. Intriguingly, the expression of NADPH oxidase genes to produce reactive oxygen species was alleviated, whereas that of antioxidant genes was enhanced in the adipose tissue of HFD-fed G6PDmut mice. In diet-induced obesity (DIO), the adipose tissue of G6PDmut mice decreased the expression of inflammatory cytokines, accompanied by downregulated proinflammatory macrophages. Accordingly, macrophages from G6PDmut mice greatly suppressed lipopolysaccharide-induced proinflammatory signaling cascades, leading to enhanced insulin sensitivity in adipocytes and hepatocytes. Furthermore, adoptive transfer of G6PDmut bone marrow to wild-type mice attenuated adipose tissue inflammation and improved glucose tolerance in DIO. Collectively, these data suggest that inhibition of macrophage G6PD would ameliorate insulin resistance in obesity through suppression of proinflammatory responses.
ISSN
0012-1797
Publisher
Amer Diabetes Assoc
DOI
http://dx.doi.org/10.2337/db16-0060
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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