Sarcopenia in the setting of nonalcoholic fatty liver

Abstract

Nonalcoholic fatty liver is a worldwide common problem with more prevalence in non-Asian populations that is closely correlated with the muscle-related disorder sarcopenia. The incidence of both health issues has been observed to be strongly interlinked where presence of one exacerbates the other. Nonalcoholic fatty liver disease (NAFLD) pathophysiology increases the muscle loss, while the onset of NAFLD in sarcopenic patients aggravates the liver problems as compared to non-sarcopenic patients. Scarcity of research on the subject provides very little evidence about the cause and effect of disorders. No FDA approved drugs are available to date for NAFLD and sarcopenia. Research is underway to understand the complex biochemical pathways involved in the development of both disorders. This review is a small contribution toward understanding sarcopenia in the setting of NAFLD that provides insight on the common pathophysiological profile of sarcopenia and NAFLD and portrays a novel way of delving into the subject by introducing the concept of cortisol crosstalk with the muscle-liver axis. Sarcopenia and NAFLD are considered metabolism-related problems, and cortisol, being a glucocorticoid, plays an important role in metabolism of fats, carbohydrates, and proteins. Cushing’s syndrome, characterized by abnormally elevated concentrations of blood cortisol/enhanced intracellular activity, shares many pathologic conditions (such as insulin resistance, metabolic syndrome, abnormal levels of specific cytokines, and obesity) with NAFLD and sarcopenia. Hence, cortisol can be a potential biomarker in sarcopenia and NAFLD. As cortisol activity at cellular level is controlled by 11β-hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1/2) enzymes that convert inactive steroid precursor into active cortisol, these enzymes can be targeted for the study of sarcopenia and NAFLD. Combined studies on NAFLD and sarcopenia with respect to cortisol open a new avenue of research in the understanding of both disorders.

Association of NAFLD/NASH, and MAFLD/MASLD with chronic kidney disease: an updated narrative review

“…For example, the role of the dyad comprising skeletal muscle and bone in this arena needs further characterization. This expectation is based on the finding that myosteatosis and sarcopenia are involved in the severity of NAFLD and MAFLD [180,181] and that advanced CKD involves a process of pseudo-ossification of media of large-and medium-caliber vessels that strongly contributes to heart failure [182,183] . Finally, the role of the liver in the risk of incident CKD also needs to be further characterized with specific reference to portal hypertension [43] .…”

The Roles of Non-Pharmacologic and Emerging Pharmacologic Management of Non-alcoholic Fatty Liver Disease and Sarcopenia: A Narrative Review

“…58 Nonetheless, both types of training downregulate circulating inflammatory markers such as IL-6, CRP, and TNF-α. 61 In a meta-analysis on the impact of endurance and combined training (i.e., endurance and resistance) on the sarcopenia criteria in NAFLD, both improved physical performance but not lean body mass. Considering most studies were endurance training protocols, this type of training may not positively impact muscle mass as compared to resistance training, which improves the power-producing capacity and sensitizes muscles to other anabolic stimuli needed in the setting of sarcopenia.…”

Effect of cofactors on NAFLD/NASH and MAFLD. A paradigm illustrating the pathomechanics of organ dysfunction

“…What is certain is that the course of NAFLD exhibits a remarkable variety of target organ dysfunction [ 48 ] . This spans from the liver (cirrhosis and HCC) (2), pancreatic beta-cell (diabetes) [ 49 ] , the kidneys (chronic kidney disease) [ 50 ] , the skeletal (sarcopenia), cardiac muscles (heart failure) [ 51 , 52 ] , and the lungs (impaired function) [ 53 , 54 ] to the development of cancer in a variety of organs [ 55 , 56 ] . What then determines such an impressively diverse clinical course in the individual subject?…”