2177-LB: Mitochondrial Infiltration of Nuclear-Derived circRNA circBirc6 Regulates ATP Synthase Assembly and Fat Differentiation, Linking Energy Metabolism to Obesity

Introduction and Objective: Impaired adipocyte differentiation contributes to insulin resistance and obesity-related type 2 diabetes. Mitochondrial dysfunction is central to impaired adipogenesis. This study investigates how nuclear-encoded circRNA circBirc6 regulates mitochondrial function and adip...

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Published inDiabetes (New York, N.Y.) Vol. 74; no. Supplement_1; p. 1
Main Authors HUANG, YANRUI, ZHU, TIANXIN, LI, YANBING, XIAO, HAIPENG, REN, MENG, SU, SHICHENG
Format Journal Article
LanguageEnglish
Published New York American Diabetes Association 20.06.2025
Subjects
Adipocytes
Adipogenesis
Adipose tissue
Animal models
ATP synthase
Body weight
Circular RNA
Diabetes
Diabetes mellitus (non-insulin dependent)
Energy metabolism
Fat metabolism
Insulin resistance
Metabolic disorders
Mitochondria
Obesity
Therapeutic targets
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Summary:Introduction and Objective: Impaired adipocyte differentiation contributes to insulin resistance and obesity-related type 2 diabetes. Mitochondrial dysfunction is central to impaired adipogenesis. This study investigates how nuclear-encoded circRNA circBirc6 regulates mitochondrial function and adipogenesis, and its role in metabolic disorders. Methods: We used obesity and adipose-specific circBirc6 knockdown mouse models, and clinical samples from obese and diabetic patients. CircBirc6 expression in adipocyte mitochondria was analyzed by high-throughput profiling. In vitro, we evaluated circBirc6 overexpression and knockdown effects on mitochondrial function and adipogenesis. Results: CircBirc6 was upregulated in the mitochondria of obese mice, negatively correlating with mitochondrial function and adipogenesis. In knockdown mice, body weight, adipose tissue volume, and insulin sensitivity improved. In patients, circBirc6 expression was elevated in omental WAT from subjects with obesity and diabetes. Overexpression of circBirc6 impaired mitochondrial function and adipogenesis. CircBirc6 binds to ATP5A and ATP5B in mitochondria, affecting ATP synthase assembly. Conclusion: CircBirc6 regulates mitochondrial function and adipogenesis, linking it to obesity-related metabolic disorders, providing a novel therapeutic target.
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ISSN:0012-1797
1939-327X
DOI:10.2337/db25-2177-LB