High-fat feeding-induced hyperinsulinemia increases cardiac glucose uptake and mitochondrial function despite peripheral insulin resistance

Anisha A. Gupte, Laurie J. Minze, Maricela Reyes, Yuelan Ren, Xukui Wang, Gerd Brunner, Mohamad Ghosn, Andrea M. Cordero-Reyes, Karen Ding, Domenico Pratico, Joel Morrisett, Zheng Zheng Shi, Dale J. Hamilton, Christopher J. Lyon, Willa A. Hsueh

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19 Scopus citations

Abstract

In obesity, reduced cardiac glucose uptake and mitochondrial abnormalities are putative causes of cardiac dysfunction. However, high-fat diet (HFD) does not consistently induce cardiac insulin resistance and mitochondrial damage, and recent studies suggest HFD may be cardioprotective. To determine cardiac responses to HFD, we investigated cardiac function, glucose uptake, and mitochondrial respiration in young (3-month-old) and middle-aged (MA) (12-month-old) male Ldlrβ/β mice fed chow or 3 months HFD to induce obesity, systemic insulin resistance, and hyperinsulinemia. In MA Ldlr -1 mice, HFD induced accelerated atherosclerosis and nonalcoholic steatohepatitis, commoncomplications of human obesity. Surprisingly, HFD-fed mice demonstrated increased cardiac glucose uptake, whichwasmost prominent inMAmice, in the absence of cardiac contractile dysfunction or hypertrophy. Moreover, hearts of HFD-fed mice had enhanced mitochondrial oxidation of palmitoyl carnitine, glutamate, and succinate and greater basal insulin signaling compared with those of chow-fed mice, suggesting cardiac insulin sensitivity was maintained, despite systemic insulin resistance. Streptozotocin-induced ablation of insulin production markedly reduced cardiac glucose uptake and mitochondrial dysfunction in HFD-fed, but not in chow-fed, mice. Insulin injection reversed these effects, suggesting that insulin may protect cardiac mitochondria during HFD. These results have implications for cardiac metabolism and preservation of mitochondrial function in obesity.

Original languageEnglish (US)
Pages (from-to)2650-2662
Number of pages13
JournalEndocrinology
Volume154
Issue number8
DOIs
StatePublished - Aug 1 2013

All Science Journal Classification (ASJC) codes

  • Endocrinology

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    Gupte, A. A., Minze, L. J., Reyes, M., Ren, Y., Wang, X., Brunner, G., Ghosn, M., Cordero-Reyes, A. M., Ding, K., Pratico, D., Morrisett, J., Shi, Z. Z., Hamilton, D. J., Lyon, C. J., & Hsueh, W. A. (2013). High-fat feeding-induced hyperinsulinemia increases cardiac glucose uptake and mitochondrial function despite peripheral insulin resistance. Endocrinology, 154(8), 2650-2662. https://doi.org/10.1210/en.2012-2272