A high‐fat diet supplemented with medium‐chain triglycerides ameliorates hepatic steatosis by reducing ceramide and diacylglycerol accumulation in mice

Abstract

Non‐alcoholic fatty liver disease (NAFLD) is projected to be the most common chronic liver disease worldwide and is closely linked to obesity, insulin resistance and type 2 diabetes. Currently, no pharmacological treatments are available to treat NAFLD, and lifestyle modification, including dietary interventions, is the only remedy. Therefore, we conducted a study to determine whether supplementation with medium‐chain triglycerides (MCTs), containing a mixture of C8 and C10 (60/40), attenuates NAFLD in obese and insulin‐resistant mice. To achieve that, we fed C57BL/6 male mice a high‐fat diet (HFD) for 12 weeks to induce obesity and hepatic steatosis, after which obese mice were assigned randomly either to remain on the HFD or to transition to an HFD supplemented with MCTs (HFD + MCTs) or a low‐fat diet (LFD) for 6 weeks as another dietary intervention model. Another group of mice was kept on an LFD throughout the study and used as a lean control group. Obese mice that transitioned to HFD + MCTs exhibited improvement in glucose and insulin tolerance tests, and the latter improvement was independent of changes in adiposity when compared with HFD‐fed mice. Additionally, supplementation with MCTs significantly reduced hepatic steatosis, improved liver enzymes and decreased hepatic expression of inflammation‐related genes to levels similar to those observed in obese mice transitioned to an LFD. Importantly, HFD + MCTs markedly lowered hepatic ceramide and diacylglycerol content and prevented protein kinase C‐ε translocation to the plasma membrane. Our study demonstrated that supplementation with MCTs formulated mainly from C8 and C10 effectively ameliorated NAFLD in obese mice.

Ceramides as Emerging Players in Cardiovascular Disease: Focus on Their Pathogenetic Effects and Regulation by Diet

“…In terms of the mechanisms underpinning the ability of medium-chain fatty acids to counter ceramide accumulation, these may rely on an increase in oxidative metabolism. Medium-chain fatty acids have been reported to act as signaling molecules able to increase the adenosine monophosphate/adenosine triphosphate ratio, leading to the activation of adenosine monophosphate-activated protein kinase with consequent inhibition of enzymes involved in anabolic pathways, including ceramide synthesis, and activation of β-oxidation [ 78 ].…”