Ketogenic Diet Superior for Liver Fat and Glycemic Control After Matched Weight Loss: Study

A new study published in the journal of Cell Metabolism showed that following comparable weight reduction, skeletal muscle, insulin sensitivity and metabolic health were enhanced by ketogenic, Mediterranean, and extremely low-fat plant-forward diets.

Obesity raises the risk of type 2 diabetes and cardiovascular disease because it is linked to atherogenic dyslipidemia, prediabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). One of the main causes of these metabolic issues is insulin resistance in the liver and skeletal muscle. Insulin sensitivity and metabolic health are enhanced by weight loss through decreased calorie intake; however, dietary macronutrient composition may have additional impacts apart from weight loss. The effectiveness of very-low-carb ketogenic, Mediterranean, and very-low-fat plant-forward diets in managing obesity may vary slightly. However, it is still unclear if these diets offer unique metabolic advantages beyond weight reduction, in part due to the limitations of earlier studies caused by variations in weight loss and poor dietary compliance.

To ascertain whether 3 diets with significantly different macronutrient compositions produce diet-specific cardiometabolic effects following comparable moderate (~10%) weight loss in people with metabolically unhealthy obesity, this trial was carried out. Before and after weight loss, they measured insulin sensitivity in the skeletal muscle and liver, body composition, intrahepatic triglycerides, hepatic de novo lipogenesis, blood pressure, plasma lipids and cytokines, 24-hour glucose, NEFA, β-hydroxybutyrate, triglyceride, and hormonal profiles, oral glucose tolerance, and β-cell function. All meals were provided, and weekly meetings with a research dietician were held to promote dietary adherence.

All groups saw a roughly 50% improvement in muscle insulin sensitivity after losing weight, but the very-low-carb group experienced a two- to three-fold increase in hepatic insulin sensitivity when compared to the other groups (p < 0.001). The very-low-carbohydrate group saw the greatest reductions in intrahepatic triglyceride content, hepatic de novo lipogenesis, glycated hemoglobin, and 24-hour serial plasma glucose and insulin.

Apolipoprotein B, LDL cholesterol, and 24-hour plasma triglyceride concentrations did not differ across the groups. Overall, this study shows how dietary macronutrient composition can significantly improve the impact of modest weight reduction on cardiometabolic health, 24-hour plasma substrate and hormone concentrations, and hepatic metabolic performance.

Source:

Petersen, M. C., Smith, G. I., Farabi, S. S., Palacios, H. H., Shankaran, M., Hellerstein, M. K., Patterson, B. W., & Klein, S. (2026). Effect of diet macronutrient content on the cardiometabolic response to weight loss: A randomized clinical trial. Cell Metabolism. https://doi.org/10.1016/j.cmet.2026.07.020