Myocyte androgen receptors increase metabolic rate and improve body composition by reducing fat mass

Area of Science:

• Endocrinology
• Muscle Physiology
• Metabolic Research

Background:

• Androgens, like testosterone, are known to influence body composition by activating the androgen receptor.
• The specific tissues and cellular mechanisms mediating these effects remain incompletely understood, limiting clinical applications.

Purpose of the Study:

• To investigate the role of androgen receptor signaling specifically within muscle cells (myocytes) in regulating body composition.
• To elucidate the cellular and metabolic changes associated with targeted androgen receptor activation in muscle.

Main Methods:

• Generation of transgenic male rats with selective overexpression of the androgen receptor in myocytes (HSA-AR rats).
• Analysis of body composition, myofiber size, adipocyte size, and metabolic parameters (mitochondrial enzyme activity, oxygen consumption) in transgenic and control animals.
• Comparison with findings from transgenic mice and testosterone-treated female rats.

Main Results:

• Selective androgen receptor overexpression in myocytes led to increased lean mass percentage and reduced fat mass.
• These compositional changes were linked to hypertrophy of type IIb myofibers and smaller adipocytes.
• Transgenic males exhibited enhanced mitochondrial enzyme activity in skeletal muscle and increased oxygen consumption.

Conclusions:

• Androgen signaling within myocytes is sufficient to increase muscle mass and decrease fat mass.
• The observed reduction in fat mass is likely mediated by increased oxidative metabolism in muscle.
• These findings provide crucial insights into the mechanisms by which androgens modulate body composition.