Abstract
Dietary protein insufficiency has been linked to excessive triglyceride storage (TG) and non-alcoholic fatty liver disease (NAFLD) in developing countries. Hepatic TG accumulation following a low-protein diet may be due to altered peroxisomal, mitochondrial and gut microbiota function. Hepatic peroxisomes and mitochondria normally mediate metabolism of nutrients to provide energy and substrates for lipogenesis. Peroxisome biogenesis and activities can be modulated by odd (OCFA) and short-chain (SCFA) fatty acids that are derived from gut bacteria e.g. propionate and butyrate. Also produced during amino acid metabolism by peroxisomes and mitochondria, propionate and butyrate correlate with reduced risk of obesity, insulin resistance and NAFLD. In this horizon-scanning review, we have compiled available evidence on the effects of protein malnutrition on OCFA production, arising from loss in mitochondrial, peroxisomal and gut microbiota function, and its association with lipid accumulation in the liver. The methyl donor amino acid composition of dietary protein is an important contributor to liver function and lipid storage; the presence and abundance of dietary branched chain amino acids can modulate the composition and metabolic activity of the gut microbiome and on the other hand, can affect protective OCFA and SCFA production in the liver. In preclinical animal models fed with low protein diets, specific amino acid supplementation can ameliorate fatty liver disease. The association between low dietary protein intake and fatty liver disease is underexplored and merits further investigation, particularly in vulnerable groups with dietary protein restriction in developing countries.