Testosterone is sequestered in dysfunctional adipose tissue, modifying androgen-responsive genes.

Area of Science:

• Endocrinology
• Adipose Tissue Biology
• Metabolic Syndrome

Background:

• Obesity is linked to male hypogonadism, affecting adipose tissue (AT) physiology.
• Testosterone (T) may sequester in fat depots, lowering circulating levels in obese individuals.
• Steroids can influence adipogenesis and lipolysis, but their role in dysfunctional AT is unclear.

Purpose of the Study:

• To investigate testosterone trafficking and activity in dysfunctional adipose tissue.
• To understand the impact of obesity on androgen signaling in subcutaneous AT.
• To explore the relationship between T accumulation and AT dysfunction.

Main Methods:

• Subcutaneous AT samples from obese and lean males were analyzed.
• Experiments were conducted on SAT explants and insulin-resistant 3T3-L1 adipocytes.
• Real-time PCR and mass spectrometry were used for quantification.

Main Results:

• Obese SAT and insulin-resistant cells showed deregulation of androgen-responsive genes.
• Reduced T release after adrenergic stimulation was observed in obese SAT.
• Higher intracellular T and estradiol concentrations were found in obese SAT, correlating with reduced lipolytic gene expression.

Conclusions:

• Dysfunctional fat cells exhibit an altered response to testosterone.
• Reduced lipolytic T release in obese SAT contributes to AT dysfunction.
• This creates a feedforward loop exacerbating hypogonadism in obese males.