Little is known about the role of specific saturated fatty acids in the development of high-fat diet-induced obesity and insulin resistance. Here, we investigated the effects of stearate in a high-fat diet (45% energy as fat) on whole-body energy metabolism and tissue-specific insulin sensitivity stearate
C57Bl/6 mice were fed either a palm oil-based low-stearate diet or one of two stearate-rich diets, a lard-based diet and a palm oil-based supplemented with tristearin diet (to reach stearate levels of a lard-based diet) for a period of 5 weeks. Oxidative metabolism was assessed by indirect calorimetry at week 5 of feeding ad libitum. Changes in body weight and composition were assessed by DEXA scan analysis. At the end of week 5, tissue-specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp analysis and Western blot.
Indirect calorimetry analysis revealed that high levels of dietary stearate resulted in lower caloric energy expenditure, characterized by lower fatty acid oxidation. Consistent with this metabolic phenotype, mice on a stearate-enriched diet gained more adipose tissue mass. Systemic and tissue-specific insulin sensitivity assessed by hyperinsulinemic-euglycemic clamp and insulin-induced PKBser473 phosphorylation assays. All high-fat diets reduce whole-body insulin sensitivity. However, while all high-fat diets impair insulin-stimulated glucose uptake in peripheral tissues, hepatic insulin sensitivity is only affected by a stearate-rich diet. This tissue-specific pattern of decreased insulin sensitivity was confirmed by similar impairments in insulin-induced phosphorylation of PKBser473 in liver and skeletal muscle.
In C57Bl/6 mice, a stearate-enriched high-fat diet for 5 weeks induced a metabolic state favoring hypooxidative metabolism, increased adiposity, and systemic insulin resistance, characterized by severe hepatic insulin resistance. These results suggest that dietary fatty acid composition itself, rather than dietary fat content, determines insulin sensitivity in the liver of high-fat-fed C57Bl/6 mice.