کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2793125 1155116 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Deletion of the Mammalian INDY Homolog Mimics Aspects of Dietary Restriction and Protects against Adiposity and Insulin Resistance in Mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
Deletion of the Mammalian INDY Homolog Mimics Aspects of Dietary Restriction and Protects against Adiposity and Insulin Resistance in Mice
چکیده انگلیسی

SummaryReduced expression of the Indy (I'm Not Dead, Yet) gene in D. melanogaster and its homolog in C. elegans prolongs life span and in D. melanogaster augments mitochondrial biogenesis in a manner akin to caloric restriction. However, the cellular mechanism by which Indy does this is unknown. Here, we report on the knockout mouse model of the mammalian Indy (mIndy) homolog, SLC13A5. Deletion of mIndy in mice (mINDY−/− mice) reduces hepatocellular ATP/ADP ratio, activates hepatic AMPK, induces PGC-1α, inhibits ACC-2, and reduces SREBP-1c levels. This signaling network promotes hepatic mitochondrial biogenesis, lipid oxidation, and energy expenditure and attenuates hepatic de novo lipogenesis. Together, these traits protect mINDY−/− mice from the adiposity and insulin resistance that evolve with high-fat feeding and aging. Our studies demonstrate a profound effect of mIndy on mammalian energy metabolism and suggest that mINDY might be a therapeutic target for the treatment of obesity and type 2 diabetes.

Graphical AbstractFigure optionsDownload high-quality image (239 K)Download as PowerPoint slideHighlights
► A mIndy (SLC13A5) knockout mouse was generated
► Loss of mIndy decreases hepatic ATP/ADP ratio and activates AMPK
► mIndy deletion promotes mitochondrial biogenesis and energy expenditure
► Loss of mIndy protects from diet- and age-associated insulin resistance

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 14, Issue 2, 3 August 2011, Pages 184–195
نویسندگان
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