Protein and amino acids in nonalcoholic fatty liver disease

In this review, the latest evidence on the influence of dietary protein and plasma amino acids in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) is discussed.

Increasing protein consumption during weight loss and maintenance may help reduce liver fat content. Conversely, high protein intake characteristic of the unhealthy Western diet is associated with increased NAFLD prevalence and severity. Plasma concentration of several amino acids, including branched-chain (BCAA) and aromatic amino acids (AAA), is altered in NAFLD. Excess amino acid availability contributes to intrahepatic fat accumulation and may reflect poor dietary habits and dysregulation of amino acid metabolic processing in both liver and peripheral tissues. Specific amino acid patterns, characterized by increased BCAA, AAA, alanine, glutamate, lysine levels, and decreased glycine and serine levels, may be used for early detection of NAFLD and noninvasive assessment of its histological severity.

Mechanistic studies in NAFLD have been mostly focused on carbohydrate and fat metabolism, while little is known about the influence of protein and amino acids. Moreover, intervention and observational studies on the relation between protein intake and NAFLD yielded conflicting results. Filling the current knowledge gaps would help define the optimal diet composition for NAFLD prevention and management. Furthermore, metabolomics studies may provide insight into the pathogenesis of NAFLD, identify useful diagnostic and prognostic biomarkers, and unravel novel pharmacological targets and treatment options.