The Role of The Mitochondrial Carrier Mtch2 And Adipocyte Dysfunction in The Pathogenesis of Metabolic Disorders in Obesity

Background: Obesity has reached pandemic proportions globally, affecting over 1 billion individuals. Recent research has identified the mitochondrial carrier MTCH2 as a key regulator of adipocyte metabolism, but its role in obesity-related metabolic dysfunction remains incompletely understood. Objective: This study aims to investigate the role of MTCH2 in adipocyte dysfunction and its contribution to metabolic disorders in obesity, with particular emphasis on patients treated at Tashkent State Medical University clinics. Methods: The study included 87 participants (43 with obesity, 44 normal-weight controls) recruited from the Endocrinology Clinic. Anthropometric measurements, biochemical profiling, and adipose tissue analysis (from 12 surgical patients) were performed. MTCH2 and CPT1 expression were quantified by real-time PCR and Western blot. MTCH2-CPT1 interaction was assessed by co-immunoprecipitation. Results: Global epidemiological analysis revealed that 45.4% of adults worldwide have abdominal obesity, with 21.7% of normal-weight individuals exhibiting abdominal obesity associated with significantly increased cardiometabolic risk. In our cohort, patients with obesity demonstrated marked leptin elevation (38.7±12.4 vs. 9.2±4.1 ng/mL, p<0.001) and hypoadiponectinemia (4.2±1.8 vs. 12.6±3.9 μg/mL, p<0.001). MTCH2 expression was 2.8-fold higher in visceral adipose tissue of patients with obesity and correlated positively with HOMA-IR (r=0.67, p<0.001). MTCH2 physically interacts with CPT1 and modulates its sensitivity to malonyl-CoA inhibition. MTCH2 overexpression reduced palmitate oxidation by 34% (p<0.01), while MTCH2 silencing increased oxidation by 52% (p<0.001). Conclusion: MTCH2 is a critical negative regulator of adipocyte mitochondrial metabolism and represents a promising therapeutic target for obesity-related metabolic disorders.

Перевод пока недоступен