卷:10 | |
Skeletal muscle mitochondrial uncoupling prevents diabetes but not obesity in NZO mice, a model for polygenic diabesity | |
Voigt, Anja ; Katterle, Yvonne ; Kahle, Melanie ; Kluge, Reinhart ; Schuermann, Annette ; Joost, Hans-Georg ; Klaus, Susanne | |
关键词: Polygenic obesity; Skeletal muscle; Uncoupling protein 1; Fibroblast growth factor 21; Diabetes; White adipose tissue; Body composition; Glucose tolerance test; Gene expression; Lipid metabolism; Glucose metabolism; | |
DOI : 10.1007/s12263-015-0507-x | |
学科分类:食品科学和技术 | |
【 摘 要 】
Induction of skeletal muscle (SM) mitochondrial stress by expression of uncoupling protein 1 (UCP1) in mice results in a healthy metabolic phenotype associated with increased secretion of FGF21 from SM. Here, we investigated whether SM mitochondrial uncoupling can compensate obesity and insulin resistance in the NZO mouse, a polygenic diabesity model. Male NZO mice were crossed with heterozygous UCP1 transgenic (tg) mice (mixed C57BL/6/CBA background) and further back-crossed to obtain F1 and N2 offspring with 50 and 75 % NZO background, respectively. Male F1 and N2 progeny were fed a high-fat diet ad libitum for 20 weeks from weaning. Blood glucose was reduced, and diabetes (severe hyperglycemia >300 mg/dl) was fully prevented in both F1- and N2-tg progeny compared to a diabetes prevalence of 15 % in F1 and 42 % in N2 wild type. In contrast, relative body fat content and plasma insulin were decreased, and glucose tolerance was improved, in F1-tg only. Both F1 and N2-tg showed decreased lean body mass. Accordingly, induction of SM stress response including FGF21 expression and secretion was similar in both F1 and N2-tg mice. In white adipose tissue, expression of FGF21 target genes was enhanced in F1 and N2-tg mice, whereas lipid metabolism genes were induced in F1-tg only. There was no evidence for induction of browning in either UCP1 backcross. We conclude that SM mitochondrial uncoupling induces FGF21 expression and prevents diabetes in mice with a 50-75 % NZO background independent of its effects on adipose tissue.
【 授权许可】
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