Topic: Immunometabolic Plasticity in Sarcopenic Obesity: From Mechanisms to Clinical and Therapeutic Perspectives

Sarcopenic obesity represents an increasingly important clinical and public health challenge, characterized by the coexistence of excess adiposity and impaired skeletal muscle mass and function. Its clinical relevance extends beyond aging populations, encompassing individuals with metabolic disorders, chronic diseases, and conditions associated with reduced physical activity or altered nutritional status. The complex interactions among adipose tissue accumulation, muscle dysfunction, metabolic disturbances, and systemic inflammation highlight the need for interdisciplinary approaches to understanding and managing this condition.

Rather than representing the simple coexistence of obesity and sarcopenia, sarcopenic obesity involves interconnected biological processes influencing body composition, physical performance, metabolic health, and clinical outcomes. These processes include adipose tissue dysfunction, skeletal muscle remodeling, chronic low-grade inflammation, insulin resistance, mitochondrial alterations, oxidative stress, hormonal dysregulation, and changes in nutrient metabolism.

An emerging area of investigation concerns the bidirectional communication among adipose tissue, skeletal muscle, and the immune system. Within this network, immunometabolic plasticity may influence tissue adaptation, inflammatory responses, metabolic flexibility, and the balance between anabolic and catabolic pathways. However, the extent to which these responses are compensatory, maladaptive, or potentially reversible remains incompletely understood.

An important dimension of this biological complexity concerns sex-related differences in immunometabolic regulation. Sex hormones, adipose tissue distribution, skeletal muscle characteristics, immune responses, and age-associated endocrine changes may influence susceptibility to sarcopenic obesity and its clinical manifestations. Investigating sex-specific immunometabolic adaptations may therefore provide valuable insights into disease heterogeneity, diagnostic approaches, and differential responses to preventive and therapeutic interventions.

The relationship between liver health and sarcopenic obesity represents another area of growing scientific interest. Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced forms frequently coexist with metabolic disturbances and alterations in skeletal muscle health. The liver participates in systemic metabolic regulation through nutrient metabolism, inflammatory signaling, and hepatokine-mediated communication. Exploring the liver-muscle-adipose tissue axis may contribute to understanding the complex and potentially bidirectional relationships among hepatic steatosis, metabolic dysfunction, muscle impairment, and disease progression.

Importantly, the pathophysiology of sarcopenic obesity cannot be fully understood without considering additional determinants, including nutritional status, physical inactivity, endocrine regulation, gut microbiota, genetic and epigenetic factors, and environmental influences. Understanding how these elements interact may provide new perspectives on individual susceptibility, disease heterogeneity, and opportunities for intervention.

From a clinical standpoint, substantial challenges remain in the identification, diagnosis, and management of sarcopenic obesity. Differences in diagnostic criteria, body composition assessment, muscle strength and performance measurements, and the interpretation of metabolic and inflammatory biomarkers complicate comparisons across studies and clinical populations. Improved diagnostic frameworks and integrated assessment strategies are therefore essential for advancing research and clinical practice.

At the same time, growing interest in nutritional interventions, resistance exercise, physical rehabilitation, pharmacological treatments, and multimodal approaches offers opportunities to investigate how muscle function, adiposity, and metabolic health can be improved. The identification of biological and clinical characteristics associated with treatment response, including sex-related differences and comorbid metabolic conditions, may contribute to more personalized therapeutic strategies.

This Special Issue, “Immunometabolic Plasticity in Sarcopenic Obesity: From Mechanisms to Clinical and Therapeutic Perspectives,” welcomes original research articles, clinical and translational studies, systematic reviews, meta-analyses, and comprehensive narrative reviews addressing the multifaceted nature of sarcopenic obesity.

Topics of particular interest include, but are not limited to:

● Molecular and cellular mechanisms underlying sarcopenic obesity, including adipose–immune–muscle crosstalk and immunometabolic regulation;

● Sex-related differences in sarcopenic obesity, including hormonal regulation, sex-specific immunometabolic adaptations, body composition, and implications for diagnosis and treatment;

● Liver health, MASLD, MASH, hepatic metabolic dysfunction, and liver–muscle–adipose tissue communication;

● Aging, inflammaging, endocrine dysfunction, insulin resistance, and metabolic disorders associated with skeletal muscle impairment;

● Mitochondrial dysfunction, oxidative stress, cellular senescence, and molecular pathways regulating muscle and adipose tissue homeostasis;

● Nutritional status, dietary patterns, protein metabolism, micronutrients, nutraceuticals, and immunonutritional strategies;

● Gut microbiota, microbial metabolites, and their potential interactions with systemic inflammation and skeletal muscle metabolism;

● Physical activity, resistance training, rehabilitation, and integrated lifestyle interventions;

● Diagnostic criteria, body composition assessment, muscle strength, physical performance, biomarkers, and risk stratification;

● Cardiometabolic, hepatic, and other chronic disease-related complications associated with sarcopenic obesity;

● Pharmacological and non-pharmacological treatments, multimodal interventions, and personalized therapeutic approaches;

● Epidemiological studies, longitudinal cohorts, prevention strategies, prognosis, and health-related quality of life.

By encouraging contributions from basic, clinical, and translational research, this Special Issue aims to promote interdisciplinary dialogue, identify critical knowledge gaps, and advance a more comprehensive understanding of sarcopenic obesity. Particular emphasis will be placed on integrating molecular mechanisms, sex-related biological variability, interorgan communication, and clinically relevant evidence to support innovative diagnostic, preventive, and therapeutic strategies.