Effects of supplementation with essential amino acids on intrahepatic lipid concentrations during fructose overfeeding in humans

Background: A high dietary protein intake has been shown to blunt the deposition of intrahepatic lipids in high-fat- and high-carbohydrate-fed rodents and humans. Objective: The aim of this study was to evaluate the effect of essential amino acid supplementation on the increase in hepatic fat content induced by a high-fructose diet in healthy subjects. Design: Nine healthy male volunteers were studied on 3 occasions in a randomized, crossover design after 6 d of dietary intervention. Dietary conditions consisted of a weight-maintenance balanced diet (control) or the same balanced diet supplemented with 3 g fructose kg(-1) . d(-1) and 6.77 g of a mixture of 5 essential amino acids 3 times/d (leucine, isoleucine, valine, lysine, and threonine) (HFrAA) or with 3 g fructose . kg(-1) . d(-1) and a maltodextrin placebo 3 times/d (HFr); there was a washout period of 4 to 10 wk between each condition. For each condition, the intrahepatocellular lipid (IHCL) concentration, VLDL-triglyceride concentration, and VLDL-[C-13]palmitate production were measured after oral loading with [C-13]fructose. Results: HFr increased the IHCL content (1.27 +/- 0.31 compared with 2.74 +/- 0.55 vol %; P < 0.05) and VLDL-triglyceride (0.55 +/- 0.06 compared with 1.40 +/- 0.15 mmol/L; P < 0.05). HFr also enhanced VLDL-[C-13]palmitate production. HFrAA significantly decreased IHCL compared with HFr (to 2.30 +/- 0.43 vol%; P < 0.05) but did not change VLDL- triglyceride concentrations or VLDL-[C-13] palmitate production. Conclusions: Supplementation with essential amino acids blunts the fructose-induced increase in IHCL but not hypertriglyceridemia. This is not because of inhibition of VLDL-[13 C] palmitate production. This trial was registered at www.clinicaltrials.gov as NCT01119989. Am J Clin Nutr 2012;96:1008-16.