Androgen receptor gene polymorphisms and maximal fat oxidation in healthy men. A longitudinal study.

Introduction: Androgens play a major role in fat oxidation; however, the effects of androgens depend, among other factors, on the intrinsic characteristics of the androgen receptor (AR). Lower repetitions of CAG and GGN polymorphism appear to have a protective effect on fat accumulation in the transition from adolescent to mid-twenties. Whether a similar protective effect is present later in life remains unknown. The aims of this study were: a) to evaluate if extreme CAG and GGN repeat polymorphisms of the androgen receptors influence body fat mass, its regional distribution, resting metabolic rate (RMR), maximal fat oxidation capacity (MFO) and serum leptin, free testosterone and osteocalcin in healthy adult men; and b) to determine the longitudinal effects on fat tissue accumulation after 6.4 years of follow-up.

Methods: CAG and GGN repeats length were measured in 319 healthy men (mean ± standard deviation [SD]: 28.3 ± 7.6 years). From these, we selected the subjects with extreme short (CAGS < or equal 19; n = 7) and long (CAGL > or equal 24; n = 10) CAG repeats, and the subjects with short (GGNS < or equal to 22; n = 9) and long (GGNL > or equal to 25; n = 10) GGN repeats. Body composition was assessed by DXA and serum levels of leptin, free testosterone and osteocalcin by ELISA. After 6.4 years of follow-up, DXA was repeated, and resting metabolic rate (RMR), MFO and VO2max determined by indirect calorimetry.

Results: CAGS and CAGL subjects had similar RMR and accumulated comparable amounts of fat tissue over 6.4 ± 1.0 years of follow-up. However, CAGL had higher MFO and total lean mass than CAGS (p < 0.05). Men with GGNS accumulated greater amount of total fat mass than men with GGNL, particularly in the trunk region seven years later. This concurred with a greater MFO in the GGNL group (p < 0.05), who accumulated less fat mass. Free testosterone was associated with MFO in absolute values (r = 0.45; p < 0.05) and MFO per kg of lower extremity lean mass per height squared (r = 0.35; p < 0.05).

Conclusiones: CAG and GGN repeat polymorphisms may influence muscle fat oxidation capacity and may have a role in the accumulation of fat over the years.