Obesity-induced TRB3 negatively regulates Brown adipose tissue function in mice

Area of Science:

• Metabolic research
• Adipose tissue biology
• Thermogenesis

Background:

• Brown adipose tissue (BAT) dissipates energy as heat via UCP1, offering potential anti-obesity and anti-diabetic effects.
• TRB3 has been shown to hinder brown preadipocyte differentiation by inhibiting insulin signaling.
• The in vivo role of TRB3 in BAT function and thermogenesis remains largely uncharacterized.

Purpose of the Study:

• To investigate the hypothesis that TRB3 mediates obesity- and diabetes-induced impairments in BAT differentiation and function.
• To determine if inhibiting TRB3 can improve BAT function and ameliorate metabolic dysfunction.

Main Methods:

• Assessed TRB3 expression in BAT from high-fat fed and ob/ob mice.
• Examined the effects of palmitate and ER stressors on TRB3 and UCP1 expression in brown adipocytes.
• Utilized TRB3 knockout (TRB3KO) mice to evaluate BAT function, thermogenesis, and metabolic responses to high-fat diet.

Main Results:

• TRB3 expression was elevated in BAT from high-fat fed and ob/ob mice, correlating with reduced UCP1 expression.
• Palmitate and ER stressors increased TRB3 expression while decreasing UCP1 in brown adipocytes; ER stress markers were elevated in obese models.
• TRB3KO mice exhibited enhanced UCP1 expression, improved cold resistance, and protection against diet-induced obesity and glucose intolerance.

Conclusions:

• High-fat feeding and obesity increase TRB3 expression in BAT, leading to impaired tissue function and thermogenesis.
• TRB3 inhibition represents a potential therapeutic strategy for combating obesity and related metabolic disorders.
• Targeting TRB3 may restore BAT function and improve energy homeostasis in metabolic diseases.