Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats

Abstract

Studies on animal models have demonstrated that feeding a low-arginine diet inhibits triacylglycerol (TAG) secretion from the liver, resulting in marked fatty liver development in rats. Here, we first showed that culturing hepatocytes in the medium mimicking the serum amino acid profile of low-arginine diet-fed rats induced TAG accumulation in the cells, indicating that the specific amino acid profile caused TAG accumulation in hepatocytes. Dietary adenine supplementation completely recovered hepatic TAG secretion and abolished hepatic TAG accumulation in rats. A comprehensive non-linear analysis revealed that inhibition of hepatic TAG accumulation by dietary adenine supplementation could be predicted using only serum amino acid concentration data. Comparison of serum amino acid concentrations indicated that histidine, methionine, and branched-chain amino acid (BCAA) concentrations were altered by adenine supplementation. Furthermore, when the serum amino acid profiles of low-arginine diet-fed rats were altered by modifying methionine or BCAA concentrations in their diets, their hepatic TAG accumulation was abolished. Altogether, these results suggest that an increase in methionine and BCAA levels in the serum in response to dietary arginine deficiency is a key causative factor for hepatic TAG accumulation, and dietary adenine supplementation could disrupt this phenomenon by altering serum amino acid profiles.

Dietary lysine restriction induces lipid accumulation in skeletal muscle through an increase in serum threonine levels in rats

“…It is well established that when growing rats are fed a diet in which the protein content is insufficient, or an essential amino acid is lacking, catabolism is enhanced, whereas anabolism is inhibited, resulting in growth retardation. Concurrently, we previously showed that neutral lipids accumulate in the liver of growing rats fed a diet deficient in protein or arginine (3)(4)(5)(6). In addition, a lysine-deficient diet increases the lipid content in the skeletal muscle of pigs (7).…”

Mechanism of the Effect of Compound Anoectochilus roxburghii (Wall.) Lindl. Oral Liquid in Treating Alcoholic Rat Liver Injury by Metabolomics

“…In this study, 22 active ingredients in CAROL were identified by UHPLC -QTOF-MS. It has been reported in the literature that these 22 active ingredients have 15 compounds were identified as having ameliorative effects on liver injury, including vanillin, 18 rutin, 19 baicalein, 20 hesperidin, 21 uridine, 22 guanosine, 23 adenine, 24 scopoletin, 25 riboflavin, 26 betaine, 27 narcissoside, 28 baicalin, 29 ursolic acid, 30 betulonic acid, 31 and citric acid. 32 The hepatoprotective effects of CAROL are attributed to these 15 active ingredients.…”

Effects of Branched-Chain Amino Acids on Skeletal Muscle, Glycemic Control, and Neuropsychological Performance in Elderly Persons with Type 2 Diabetes Mellitus: An Exploratory Randomized Controlled Trial

“…Serum metabolite analyses were performed as previously described [ 40 ]. Briefly, 50 μL of serum samples were mixed with methanol to remove macromolecules, such as proteins.…”