期刊
MOLECULAR ENDOCRINOLOGY
卷 27, 期 11, 页码 1887-1896出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/me.2013-1137
关键词
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资金
- Pediatric Scientist Development Program National Institutes of Health [5K12HD000850-27]
- Digestive Diseases Research Core Center [P30 DK52574, R01DK078187, R01HD040390-07]
- Diabetes Research and Training Center [P60 DK020579]
Members of the glucose transporter (GLUT) family of membrane-spanning hexose transporters are subjects of intensive investigation for their potential as modifiable targets to treat or prevent obesity, metabolic syndrome, and type 2 diabetes mellitus. Mounting evidence suggests that the ubiquitously expressed class III dual-specificity glucose and fructose transporter, GLUT8, has important metabolic homeostatic functions. We therefore tested the hypothesis that GLUT8 mediates the deleterious metabolic effects of chronic high-fructose diet exposure. Here we demonstrate resistance to high-fructose diet-induced glucose intolerance and dyslipidemia concomitant with enhanced oxygen consumption and thermogenesis in GLUT8-deficient male mice. Independent of diet, significantly lower systolic blood pressure both at baseline and after high-fructose diet feeding was also observed by tail-cuff plethysmography in GLUT8-deficient mice vs wild-type controls. Resistance to fructose-induced metabolic dysregulation occurred in the context of enhanced hepatic peroxisome proliferator antigen receptor-gamma (PPAR gamma) protein abundance, whereas in vivo hepatic adenoviral GLUT8 overexpression suppressed hepatic PPAR gamma expression. Taken together, these findings suggest that GLUT8 blockade prevents fructose-induced metabolic dysregulation, potentially by enhancing hepatic fatty acid metabolism through PPAR gamma and its downstream targets. We thus establish GLUT8 as a promising target in the prevention of diet-induced obesity, metabolic syndrome, and type 2 diabetes mellitus in males.
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