The Impact of Short-term Eucaloric Low-Carbohydrate and High-Carbohydrate Diet on Liver Triacylglycerol Content in Males with Overweight and Obesity; a Randomized Cross-Over Study.

BACKGROUND:Intrahepatic triacylglycerol (liver TG) content is associated with hepatic insulin resistance and dyslipidemia. Liver TG content can be modulated within days under hypocaloric conditions. OBJECTIVE:We hypothesized that four days of eucaloric low-carbohydrate/high-fat (LC) intake would decrease liver TG content while a high-carbohydrate/low-fat (HC) intake would increase liver TG content, and further that alterations in liver TG would be linked to dynamic changes in hepatic glucose and lipid metabolism. METHODS:A randomized cross-over trial in males with 4 days + 4 days of LC and HC, respectively, with at least 2 weeks of wash-out. 1H-Magnetic Resonance Spectroscopy (1H-MRS) was used to measure liver TG content, with metabolic testing before and after intake of LC diet (11E% carbohydrate corresponding to 102±12 (mean±SD) g/day, 70E% fat) and a HC diet (65E% carbohydrate corresponding to 537±56 g/day, 16E% fat). Stable [6,6-2H2]-glucose and [1,1,2,3,3-D5]-glycerol tracer infusions combined with hyperinsulinemic-euglycemic clamps and indirect calorimetry were used to measure rates of hepatic glucose production (HGP) and lipolysis, whole body insulin sensitivity and substrate oxidation. RESULTS:Eleven normoglycemic males with overweight or obesity (BMI 31.6±3.7 kg/m2) completed both diets. The LC diet reduced liver TG content by 35.3% (95%CI: -46.6;-24.1) from 4.9 % [2.4-11.0] (median [IQR]) to 2.9% [1.4-6.9], while there was no change after the HC diet. After the LC diet, fasting whole-body fat oxidation and plasma beta-hydroxybutyrate concentration increased, while markers of de novo lipogenesis diminished. Fasting plasma TG and insulin concentrations were lowered and the hepatic insulin sensitivity index (HISI) increased after LC. Peripheral glucose disposal was unchanged. CONCLUSION:Reduced carbohydrate and increased fat intake for four days induced a marked reduction in liver TG content and increased hepatic insulin sensitivity. Increased rates of fat oxidation and ketogenesis combined with lower rates of de novo lipogenesis are suggested to be responsible for lowering of liver TG. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE WHERE IT WAS OBTAINED: clinicaltrials.gov (NCT04581421).