Browsing by keyword "Fatty Acids, Nonesterified"
Now showing items 1-2 of 2
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Lipid droplets: FSP27 knockout enhances their sizzleFat-specific protein of 27 kDa (FSP27) is a highly expressed adipocyte protein that promotes triglyceride accumulation within lipid droplets. In this issue of the JCI, Nishino et al. show that FSP27 also helps to maintain the characteristically large unilocular lipid droplet structure within each white adipocyte (see the related article beginning on page 2808). Fragmentation of lipid droplets in white adipocytes from FSP27-KO mice caused both increased lipolysis and upregulation of genes enhancing mitochondrial oxidative metabolism. This increased energy expenditure in turn protected the mice from diet-induced obesity and insulin resistance. These new results highlight powerful mechanisms that tightly coordinate rates of triglyceride storage in lipid droplets with mitochondrial fatty acid oxidation in white adipocytes.
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Nutrient stress activates inflammation and reduces glucose metabolism by suppressing AMP-activated protein kinase in the heartOBJECTIVE: Heart failure is a major cause of mortality in diabetes and may be causally associated with altered metabolism. Recent reports indicate a role of inflammation in peripheral insulin resistance, but the impact of inflammation on cardiac metabolism is unknown. We investigated the effects of diet-induced obesity on cardiac inflammation and glucose metabolism in mice. RESEARCH DESIGN AND METHODS: Male C57BL/6 mice were fed a high-fat diet (HFD) for 6 weeks, and heart samples were taken to measure insulin sensitivity, glucose metabolism, and inflammation. Heart samples were also examined following acute interleukin (IL)-6 or lipid infusion in C57BL/6 mice and in IL-6 knockout mice following an HFD. RESULTS: Diet-induced obesity reduced cardiac glucose metabolism, GLUT, and AMP-activated protein kinase (AMPK) levels, and this was associated with increased levels of macrophages, toll-like receptor 4, suppressor of cytokine signaling 3 (SOCS3), and cytokines in heart. Acute physiological elevation of IL-6 suppressed glucose metabolism and caused insulin resistance by increasing SOCS3 and via SOCS3-mediated inhibition of insulin receptor substrate (IRS)-1 and possibly AMPK in heart. Diet-induced inflammation and defects in glucose metabolism were attenuated in IL-6 knockout mice, implicating the role of IL-6 in obesity-associated cardiac inflammation. Acute lipid infusion caused inflammation and raised local levels of macrophages, C-C motif chemokine receptor 2, SOCS3, and cytokines in heart. Lipid-induced cardiac inflammation suppressed AMPK, suggesting the role of lipid as a nutrient stress triggering inflammation. CONCLUSIONS: Our findings that nutrient stress activates cardiac inflammation and that IL-6 suppresses myocardial glucose metabolism via inhibition of AMPK and IRS-1 underscore the important role of inflammation in the pathogenesis of diabetic heart.
