Abstract
BackgroundRelatively 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 have studied the effect of stearate in high fat diets (45% energy as fat) on whole body energy metabolism and tissue specific insulin sensitivity.MethodsC57Bl/6 mice were fed a low stearate diet based on palm oil or one of two stearate rich diets, one diet based on lard and one diet based on palm oil supplemented with tristearin (to the stearate level of the lard based diet), for a period of 5 weeks. Ad libitum fed Oxidative metabolism was assessed by indirect calorimetry at week 5. Changes in body mass and composition was assessed by DEXA scan analysis. Tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp analysis and Western blot at the end of week 5.ResultsIndirect calorimetry analysis revealed that high levels of dietary stearate resulted in lower caloric energy expenditure characterized by lower oxidation of fatty acids. In agreement with this metabolic phenotype, mice on the stearate rich diets gained more adipose tissue mass. Whole body and tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp and analysis of insulin induced PKBser473 phosphorylation. Whole body insulin sensitivity was decreased by all high fat diets. However, while insulin-stimulated glucose uptake by peripheral tissues was impaired by all high fat diets, hepatic insulin sensitivity was affected only by the stearate rich diets. This tissue-specific pattern of reduced insulin sensitivity was confirmed by similar impairment in insulin-induced phosphorylation of PKBser473 in both liver and skeletal muscle.ConclusionIn C57Bl/6 mice, 5 weeks of a high fat diet rich in stearate induces a metabolic state favoring low oxidative metabolism, increased adiposity and whole body insulin resistance characterized by severe hepatic insulin resistance. These results indicate that dietary fatty acid composition per sé rather than dietary fat content determines insulin sensitivity in liver of high fat fed C57Bl/6 mice.
Highlights
High fat diets are widely used to study the development of obesity and insulin resistance in rodent models
The effect of dietary stearate on whole body energy metabolism To determine whether a high level of dietary stearate induces changes in whole body substrate selection or energy metabolism, three high fat diets were evaluated: a low stearate diet based on palm oil (HFP, containing 4.4% stearate) and two stearate rich diets based on lard (HFL, containing 15.0% stearate) or the palm oil diet supplemented with tristearin (HFPS, containing 13.9% stearate)
The animals fed the stearate rich High Fat Palm oil diet (HFP) controls (HFL) and HFPS diets exhibited significant lower energy expenditure rates compared to animals fed the HFP diet
Summary
High fat diets are widely used to study the development of obesity and insulin resistance in rodent models. Different high fat diets clearly induce different effects [1,2,3], it has been a challenge to assign specific effects to individual fatty acids. This is of interest and relevance for differential effects of the saturated long chain fatty acids (FA). Oxidative efficiency of FA decreases with increasing chain length and saturation level. Little is known about the role of specific saturated fatty acids in the development of high fat diet induced obesity and insulin resistance. We have studied the effect of stearate in high fat diets (45% energy as fat) on whole body energy metabolism and tissue specific insulin sensitivity
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