Nutrition and Alcoholic Liver Disease: Effects of Alcoholism on Nutrition, Effects of Nutrition on Alcoholic Liver Disease, and Nutritional Therapies for Alcoholic Liver Disease

Abstract

Malnutrition is the most frequent and nearly universal consequence in alcoholic liver disease (ALD) that adversely affects clinical outcomes. Sarcopenia or skeletal muscle loss is the major component of malnutrition in liver disease. There are no effective therapies to prevent or reverse sarcopenia in ALD because the mechanisms are not well understood. Consequences of liver disease including hyperammonemia, hormonal perturbations, endotoxemia and cytokine abnormalities as well as the direct effects of alcohol and its metabolites contribute to sarcopenia in ALD. This article focuses on the prevalence, methods to quantify malnutrition, specifically sarcopenia and potential therapies including novel molecular targeted treatments.

Keywords: Alcoholic liver disease; Malnutrition; Mitochondria; Molecular pathways; Myostatin; Reactive oxygen species; Sarcopenia; Skeletal muscle loss.

Figure 1. Schematic of mediators of sarcopenia in alcoholic liver disease

A number of factors contribute to sarcopenia in ALD including the direct effects of ethanol or its metabolism in the muscle as well as ethanol-induced liver disease with consequent hyperammonemia as well as non-hepatic factors including gut-derived endotoxemia and cytokine-mediated effects.

Figure 2. Schematic of putative molecular pathways contributing to sarcopenia of liver disease

Ethanol or its metabolites (primarily acetaldehyde) activate a number of pathways either via myostatin or reactive oxygen species-mediated impairment of critical molecular signaling component, mammalian target of rapamycin complex 1 (mTORC1) with reduced protein synthesis and increased autophagy, both of which contribute to sarcopenia and loss of muscle mass. Dephosphorylation of critical regulatory proteins (mTORC1, DRP1) at specific sites causes perturbation of downstream signaling responses. AMPK AMP kinase; DRP1 dynamin related protein 1 (mitochondrial fission regulatory protein); PP2A protein phosphatase 2 A; PI3Kγ Phosphoinositide 3 kinase gamma isoform; ROS reactive oxygen species.