Chronic intake of high-fat and high-sucrose diets differentially affects glucose intolerance in mice

Intakes of some macronutrients can comprise risk factors for life-style-related diseases such as obesity, hyperlipidemia, diabetes, hypertension, and atherosclerosis. In this study, we examined the effects in C57BL/6J mice of consuming excess fat or sucrose for a long period of time (55 wk). Another group of mice consumed a low-fat, low-sucrose (ILL) diet. Mice fed the high-fat (HF) diet gained weight and developed hyperlipidemia and hyperleptinemia. At 25 wk, but not at 55 wk, hepatic glucose-6-phosphatase (G6Pase) activity of the mice fed the high sucrose (HS) diet was greater than that of mice fed the ILL or HF diet. Those fed the HS diet were not obese and had greater hepatic lipogenic and gluconeogenic enzyme activities. The HF and HS diets resulted in different types of glucose intolerance. In an oral glucose tolerance test, mice fed the HF diet had a delay in the clearance of glucose compared with those fed the ILL diet, perhaps due to the peripheral insulin resistance that resulted from higher levels of circulating free fatty acids. Feeding the HS diet for 55 wk induced hyperglycemia 10 min after oral glucose administration, although blood glucose declined rapidly after i.p. insulin injection. This finding suggests that the effects of chronic HS diet intake may be due to the reduction in early insulin secretion from pancreatic islets and the increase in sucrase activity in the small intestine. It is important to consider the effects of macronutrients in lean as well as obese mice to clarify the pathogenesis of the metabolic disorders.