“Dietary fat, particularly saturated fat, has been considered harmful for decades,” explains senior author Bente Kiens. “However, more and more epidemiological studies refute this ‘fat scare’, but no solid mechanistic intervention studies in humans have been conducted to underpin such statements.” Now, new research shows that eating a high-fat diet (HFD) that is calorically balanced causes metabolic adaptations that prevent metabolic complications, such as reduced insulin sensitivity.

The authors conducted a randomized parallel intervention study and assigned 18 healthy, untrained and slightly overweight men to either a HFD rich in polyunsaturated or saturated fat for 6 weeks. Both diets were eucaloric to maintain bodyweight.

Kiens and colleagues observed that participants in both diet intervention groups maintained their insulin sensitivity at the whole-body level. Analysis of skeletal muscle biopsy samples taken from the volunteers showed that the expression of lipid transporters and intracellular fatty acid handling proteins were increased after the HFD intervention. Fatty acid oxidation was also elevated, suggesting that in response to a HFD skeletal muscles induced fatty acid uptake and oxidation instead of fat storage. Insulin sensitivity in the skeletal muscle was unaffected by HFD, which supported the observation that insulin sensitivity was maintained at the whole-body level. Additionally, hepatic insulin clearance increased and gluconeogenesis and fasting plasma levels of triacylglycerol decreased, suggesting a change towards a non-diabetic direction.

Furthermore, mice fed the same HFD as humans also maintained their insulin sensitivity. Analysis of liver-specific changes in mice fed a HFD suggests that the liver decreases gluconeogenesis and lipogenesis to adapt to a diet rich in fat. “Thus, if you avoid caloric surplus then a fat-rich diet, be it polyunsaturated or saturated, is not detrimental to health, but in fact has several health benefits.” concludes Kiens.