Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice

Area of Science:

• Endocrinology
• Metabolic research
• Lipid metabolism

Background:

• Sex steroids significantly influence adipose tissue metabolism in men.
• Androgens can impact metabolism directly via androgen receptors (AR) or indirectly through estrogen conversion.
• Estrogen receptor alpha stimulation is known to decrease fat mass in men.

Purpose of the Study:

• To investigate the specific role of androgen receptor (AR) activation in regulating adipose tissue metabolism.
• To elucidate the direct effects of androgens on metabolic processes independent of estrogen pathways.

Main Methods:

• Orchidectomized mice were administered 5alpha-dihydrotestosterone (DHT), a non-aromatizable androgen, 17beta-estradiol, or a vehicle control.
• Key metabolic parameters including oxygen consumption (Vo2), carbon dioxide production (Vco2), resting metabolic rate, activity, and food intake were measured.
• Hepatic gene expression was analyzed to assess molecular changes.

Main Results:

• DHT administration resulted in significant obesity, characterized by reduced energy expenditure and impaired fat oxidation.
• While DHT did not alter food consumption or locomotor activity, it increased high-density lipoprotein-cholesterol and triglyceride levels.
• DHT treatment led to decreased 7alpha-hydroxylase gene expression, suggesting reduced bile acid production.

Conclusions:

• Androgen receptor (AR) activation directly promotes obesity and dysregulates lipid metabolism in male mice.
• These findings suggest that AR antagonists could be a potential therapeutic strategy for managing obesity in men.