High Incidence of Lipid Deposition in the Liver of Rats Fed a Diet Supplemented with Branched-Chain Amino Acids under Vitamin B6 Deficiency

Abstract

73Branched-chain amino acids (BCAAs) composed of valine, leucine, and isoleucine are essential amino acids and account for about 40% of dietary essential amino acids in body protein and about 15% of total amino acids in muscle proteins (1). BCAAs play a role in delayed onset of muscle soreness and fatigue, and suppression of fatigue in the central nervous system (2, 3). BCAAs have been also used for the prevention of hepatic encephalopathy in patients with liver cirrhosis (4, 5). Recently, sport enthusiasts have created an increased demand for dietary supplements with BCAAs and have increased their consumption of BCAAs-enriched soft drinks.The first step in the catabolism of BCAAs involves branched-chain aminotransferase (BCAT; EC 2.6.1.42), a common enzyme. This enzyme requires vitamin B 6, which functions as a cofactor in many enzyme reactions of amino acid metabolism (6, 7). However, little information is available on the relationship between supplementation with BCAAs and the recommended daily allowance of vitamin B6. In addition, it is known that a high-protein diet (e.g., 70% casein diet) under vitamin B6 deficiency has a negative impact on several biochemical parameters and leads to fatty liver in rats (8-10).Our previous study showed that providing supplemented BCAAs under vitamin B6 deficiency and a 20% casein diet caused an accumulation of triacylglycerol in the liver, and individual differences in biological responses were observed (11). It is possible that a disorder of amino acid metabolism in the presence of vitamin B6 deficiency might influence the assembly of lipids and apolipoproteins and/or the secretion of lipoproteins. Among the serum lipoproteins, very low-density lipoprotein (VLDL) is present during endogenous lipogenesis in the liver and its major apolipoproteins are apolipoprotein (apo) B, apo C, and apo E (12). It is interesting to compare serum apo B and apo E levels, and hepatic apoE levels to evaluate lipid deposition, because apo B and apo E are key determinants responsible for cellular recognition and internalization of chylomicron remnants, VLDL, and high-density lipoprotein (HDL) (13,14). In this study, we investigated the possible mechanism of lipid deposition in the liver of rats fed with the supplementation of BCAA under vitamin B 6 deficiency and suggested the presence of impaired secretion of VLDL into the bloodstream from the liver. Materials and MethodsDiets and animals. Four diets composed of purified 20% vitamin-free casein diet with (1) or without (2) vitamin B6 (7.0 mg of pyridoxine HCl/kg of diet) and with (1) or without (2) Summary Male Wistar rats were fed four diets composed of purified 20% vitamin-free casein diet with (1) or without (2) vitamin B6 (7.0 mg of pyridoxine HCl/kg of diet) and with (1) or without (2) branched-chain amino acids (BCAAs) of valine, leucine, and isoleucine (4.75%): B6 (1)BCAA (2); B6(1)BCAA(1); B6 (2)BCAA (2); and B6 (2)BCAA (1) for 21 d. Among rats fed the B6(2)BCAA(1) diet, about a half showed lipid deposition in the liver. On the other...

Choline and betaine ameliorate liver lipid accumulation induced by vitamin B6 deficiency in rats

“…It was reported that B 6 deficiency induced fat deposition in the livers of rats fed with 70% casein diet or 4.75% branched-chain amino acidsupplemented diet. 1,2) Similarly, in our previous studies, rats fed a B 6 -deficient diet supplemented with L-Met (0.9%) developed severe hyperhomocysteinemia accompanied by lipid deposition in the liver. 3,4) We speculated that the accumulation of liver lipids was due to decreased secretion of very low-density lipoprotein (VLDL) from the liver.…”

Accumulation of lipid in rat liver was induced by vitamin B6 deficiency and was ameliorated by supplemental phosphatidylcholine in the diet

“…4,28,29) In addition, serum PC concentration was significantly lower in B 6 -deficient rats than in pair-fed controls. 29) In an analogous fashion, Kaimoto et al 30) reported that about 50% of rats fed a diet supplemented with branched-chain amino acids during B 6 deficiency showed lipid deposition in the liver and tended to have decreased serum TG levels. Moreover, they found that rats with liver lipid deposition also had decreased TG and TC levels in VLDL.…”

Long-term intake of a high-protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats

“…An increased TG synthesis capacity in liver with a concomitant reduction of hepatic VLDL-related TG secretion could help to explain the higher hepatic TG content observed in animals fed with HP diet. It has been previously reported that rats supplemented with branched-chain amino acids under vitamin B6 deficiency showed TG deposition in liver partly explained by impaired secretion of VLDL [44]; this could be relevant as casein, our dietary protein source, is rich in branched-chain amino acids. Intriguingly, other authors have reported reduced liver fat accumulation in rodents with long term increase of the protein content of the diet [45][46][47][48].…”