Opposing effects of dietary sugar and saturated fat on cardiovascular risk factors and glucose metabolism in mitochondrially impaired mice

Both dietary fat and dietary sucrose are major components of Western diets that may differentially affect the risk for body mass gain, diabetes mellitus, and cardiovascular disease. We have phenotypically analyzed mice with ubiquitously impaired expression of mitochondrial frataxin protein that were challenged with diets differing in macronutrient content, namely high-sucrose/low-fat and high-saturated fat/low-sugar diets. We find here that a high-sucrose/low-fat diet has especially detrimental effects in mice with impaired mitochondrial metabolism promoting several independent cardiovascular risk factors, including impaired glucose metabolism, fasting hyperinsulinemia, reduced glucose-stimulated insulin secretion, increased serum triglycerides, and elevated cholesterol levels due to increased expression of HMG-CoA reductase. In contrast, a high-saturated fat/low-sugar diet protects mice with impaired mitochondrial metabolism from diet-induced obesity by increasing total energy expenditure and increasing expression of ACAA2, a rate-limiting enzyme of mitochondrial beta-oxidation, whereas no concomitant improvement of glucose metabolism was observed. Taken together, our results suggest that mitochondrial dysfunction may cause sucrose to become a multifunctional cardiovascular risk factor, whereas low-sugar diets high in saturated fat may prevent weight gain without improving glucose metabolism.