LMO3 reprograms visceral adipocyte metabolism during obesity

Area of Science:

• Molecular Biology
• Metabolic Diseases
• Adipocyte Biology

Background:

• Obesity and altered body fat distribution are significant risk factors for type 2 diabetes and metabolic syndrome.
• Adipocyte behavior differences across fat depots contribute to metabolic risk.
• The function of LIM domain only 3 (LMO3) in visceral adipocytes is largely unknown.

Purpose of the Study:

• To investigate the role of LMO3-dependent pathways in modulating mature adipocyte functions during obesity.
• To determine if LMO3 can improve metabolic parameters in diet-induced obesity.

Main Methods:

• Adeno-associated virus (AAV) serotype Rec2 was used to deliver Lmo3 or YFP to epididymal white adipose tissue (eWAT) in mice on a high-fat diet (HFD).
• In vitro studies utilized 3T3-L1 adipocytes and primary human mature adipocytes with engineered LMO3 expression.
• Assessed insulin sensitivity, glucose uptake, insulin signaling, adipocyte bioenergetics, and endocrine function.

Main Results:

• AAV-mediated Lmo3 expression in eWAT improved insulin sensitivity and promoted healthy visceral adipose tissue expansion in HFD mice, increasing serum adiponectin.
• In vitro, LMO3 enhanced PPARγ activity, insulin-stimulated GLUT4 translocation, glucose uptake, and mitochondrial oxidative capacity.
• LMO3 induced nuclear coactivator 1 (Ncoa1), which was essential for LMO3's effects on glucose uptake and mitochondrial gene expression.

Conclusions:

• LMO3 acts as a novel regulator that improves visceral adipose tissue function during obesity.
• LMO3 enhances glucose metabolism, insulin sensitivity, and mitochondrial function in adipocytes, counteracting HFD-induced adipose dysfunction.
• The LMO3-Ncoa1 axis is critical for preserving adipocyte functionality and metabolic health.