The role of peroxisomes in skeletal muscles in high-fat diet-induced obesity

Peroxisome biogenesis disorders (PBDs) are a group of rare genetic conditions characterized by the impaired peroxisome formation or function. These disorders are typically caused by mutations in genes encoding peroxisomal proteins involved in peroxisome assembly, import, or metabolism. Individuals with PBDs have dysfunctional or absent peroxisomes, leading to a wide range of severe and often life-threatening clinical symptoms. PBDs includes several disorders with varying degrees of severity, including Zellweger spectrum disorders (ZSDs), rhizomelic chondrodysplasia punctata (RCDP), and single peroxisome enzyme deficiencies. The clinical features of PBDs can involve multiple organ systems, such as brain, liver, kidneys, and skeletal system. Symptoms may include developmental delay, intellectual disability, hearing and vision impairment, skeletal abnormalities, liver dysfunction, and respiratory difficulties. Studying peroxisomes is crucial for several reasons: 1. Understanding peroxisome biology: Peroxisomes have diverse functions, such as lipid metabolism, fatty acid oxidation, detoxification of reactive oxygen species, and biosynthesis of important molecules like bile acids and plasmalogens. Investigating peroxisomes can deepen our knowledge of these vital organelles. 2. Link to human health and disease: Peroxisomal dysfunction, as seen in PBDs, leads to severe metabolic disorders and organ dysfunction. Exploring the molecular mechanisms underlying peroxisomal disorders can provide insights into disease pathology and potential therapeutic targets. 3. Metabolic regulation: Peroxisomes play a significant role in lipid metabolism and energy homeostasis. Dysfunctional peroxisomes can impact lipid metabolism, leading to metabolic disorders such as obesity, dyslipidemia, and insulin resistance. 4. Drug and therapy development: Understanding the underlying mechanisms of peroxisomal disorders can identify potential targets for drug development and gene therapies. 5. Insights into cellular dynamics: Peroxisomes interact with other organelles, such as mitochondria, endoplasmic reticulum, and lipid droplets, to coordinate cellular functions. Researching this interplay provides insights into cellular communication. Obesity is a global health concern, and its high prevalence calls for more research to understand its underlying molecular mechanisms and identify potential therapeutic targets. One area of growing interest is the role of peroxisomes in the development and progression of obesity. Skeletal muscle is a major site for energy expenditure and lipid metabolism. Perturbations in skeletal muscle lipid metabolism have been implicated in the pathogenesis of obesity. Peroxisomes, characterized by their unique enzymatic machinery, play a crucial role in fatty acid oxidation and cellular lipid homeostasis maintenance. Peroxisomal dysfunction has been observed in obesity-related disorders, suggesting their potential involvement in the development of metabolic abnormalities. Furthermore, recent studies have highlighted the interplay between peroxisomes and other cellular compartments, such as mitochondria and endoplasmic reticulum, in the regulation of skeletal muscle metabolism. Peroxisomal biogenesis factors, including PEX proteins, have been found to influence mitochondrial function and insulin signaling pathways, suggesting intricate crosstalk between these organelles in the context of obesity. Understanding the role of peroxisomes in skeletal muscle metabolism during high-fat diet-induced obesity is crucial for the development of targeted therapeutic interventions. In conclusion, targeting peroxisomal pathways represents a potential therapeutic approach for mitigating the deleterious effects of obesity.