Striatal dopamine 2 receptor upregulation during development predisposes to diet-induced obesity by reducing energy...

Area of Science:

• Neuroscience
• Metabolic Research
• Obesity Studies

Background:

• Dopaminergic signaling, specifically at dopamine 2 receptors (D2R) in the striatum, is implicated in obesity research.
• Previous human studies show conflicting results regarding D2R variations and obesity risk, suggesting a complex relationship.
• Animal studies indicate chronic obesogenic diets decrease striatal D2R function, but D2R down-regulation doesn't cause obesity.

Purpose of the Study:

• To investigate the consequences of striatal D2R up-regulation on body weight gain and energy balance.
• To determine if increased striatal D2R function contributes to obesity susceptibility.
• To elucidate the underlying mechanisms linking striatal D2R levels to energy homeostasis.

Main Methods:

• Utilized a mouse model with selective D2R overexpression (D2R-OE) in striatal medium spiny neurons.
• Assessed body weight gain, energy expenditure, and eating behavior in D2R-OE mice.
• Examined the effects of developmental D2R-OE on long-term obesity and energy balance.

Main Results:

• Striatal D2R-OE led to reduced brown adipose tissue thermogenesis and decreased overall energy expenditure.
• Mice with striatal D2R-OE exhibited accelerated obesity despite reduced food intake.
• Developmental D2R-OE was sufficient to promote obesity and induce persistent energy balance deficits.

Conclusions:

• Striatal D2R up-regulation promotes obesity by impairing energy expenditure, particularly thermogenesis.
• Early-life alterations in the striatal dopamine system can persistently increase obesity predisposition.
• These findings highlight a pathological mechanism where increased striatal D2R function contributes to obesity development.