Sarcopenia and Metabolic Dysfunction in Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and sarcopenia share interconnected pathophysiological pathways. NAFLD is defined by excessive hepatic lipid accumulation in the absence of significant alcohol consumption, spanning a spectrum from benign steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Sarcopenia, characterised by progressive loss of skeletal muscle mass and function, has emerged as both a consequence and a driver of metabolic dysfunction in NAFLD. The muscle–liver axis encompasses a network of endocrine and paracrine signals, including insulin, myokines and hepatokines, which regulate energy homeostasis, inflammation and substrate metabolism. Insulin resistance, systemic inflammation and ectopic fat deposition underlie both conditions, creating a vicious cycle whereby hepatic steatosis exacerbates muscle catabolism and reduced muscle mass worsens glucose and lipid handling in the liver. Clinical phenotypes such as sarcopenic obesity and myosteatosis—fat infiltration of muscle—further complicate prognosis by enhancing the risk of disease progression, adverse metabolic outcomes and physical disability. Therapeutic approaches targeting both hepatic and muscular compartments, including lifestyle intervention, exercise training and agents modulating anabolic and catabolic pathways, hold promise for interrupting this bidirectional deterioration.

Research from Nature Portfolio

Recent studies have highlighted the gut–liver–muscle axis as a key modulator of NAFLD severity. Analysis of gut microbiota in obese patients revealed that shifts in microbial composition correlate with both liver fibrosis and muscle fat infiltration, suggesting a microbiome-mediated link in disease progression. Reduced abundance of specific bacterial taxa was associated with increased measures of steatohepatitis and myosteatosis, pointing to potential microbial biomarkers and targets for intervention. In population-based analyses, grip strength adjusted for body weight emerged as an independent predictor of fatty liver prevalence. Higher muscle strength was inversely associated with hepatic steatosis and transaminase elevations, underscoring the prognostic value of simple functional measures in identifying individuals at risk of NAFLD.

Sarcopenia and Metabolic Dysfunction in Non-Alcoholic Fatty Liver Disease publication trend

The graph below shows the total number of articles in sarcopenia and metabolic dysfunction in non-alcoholic fatty liver disease across all publications each year (not limited to Nature Index journals).

Technical terms

Sarcopenia: Progressive decline in skeletal muscle mass, strength and performance.

Non-alcoholic fatty liver disease (NAFLD): Spectrum of liver disorders characterised by excessive lipid accumulation in hepatocytes not due to alcohol use.

Myosteatosis: Infiltration of lipid into skeletal muscle fibres, impairing muscle quality.

Steatohepatitis: Inflammatory subtype of NAFLD marked by hepatocellular injury and immune cell infiltration.

Insulin resistance: Reduced responsiveness of tissues to insulin, leading to impaired glucose uptake and metabolism.

References

1. ADAR2 deficiency ameliorates non‐alcoholic fatty liver disease and muscle atrophy through modulating serum amyloid A1. Journal of Cachexia Sarcopenia and Muscle (2024).
2. Myosteatosis rather than sarcopenia associates with non‐alcoholic steatohepatitis in non‐alcoholic fatty liver disease preclinical models. Journal of Cachexia Sarcopenia and Muscle (2020).
3. Relationship of sarcopenia with steatohepatitis and advanced liver fibrosis in non-alcoholic fatty liver disease: a meta-analysis. BMC Gastroenterology (2018).
4. Relationship between grip strength and newly diagnosed nonalcoholic fatty liver disease in a large-scale adult population. Scientific Reports (2016).
5. Microbiota analysis and transient elastography reveal new extra-hepatic components of liver steatosis and fibrosis in obese patients. Scientific Reports (2021).