Impact of diet-induced obesity in male mouse reproductive system: The
role of advanced glycation end product-receptor for advanced glycation
end product axis
Obesity represents a route to broad physiological dysfunction affecting
major organs including male urogenital system. Hyperglycemia,
hyperlipidemia, and oxidative stress associated with obesity augment the
formation of reactive metabolic by-products, namely advanced glycation
end products (AGEs), leading to increased tissue deposition and damage.
The exogenous intake and the endogenous accumulation of AGEs contribute
to metabolic and reproductive abnormalities in both women and men. The
present study assessed the effects of a diet high in saturated fatty
acids (SAFA) on the lipid and metabolic profile (AGE levels, oxidative
stress) as well as pathogenic (AGE, receptor for AGEs [RAGE]
expression, apoptosis) and morphometric parameters of male reproductive
system in vivo. Effects of switching to a diet rich in monounsaturated
fatty acids (MUFA) or equal in the proportion MUFA to SAFA were further
investigated. SAFA-fed animals were characterized by increased serum
lipid concentrations (p < .05) compared to controls, but AGEs and
peroxide levels were not significantly different across the different
experimental groups. Elevated AGE deposition was detected for the first
time in germ cells with a higher staining intensity in animals on the
SAFA diet, compared to MUFA or MUFA-SAFA-fed animals or the control
samples (p = .018). In Leydig cells, AGE localization was higher in the
entire cohort of high-fat-fed animals compared to controls (p < .05).
High-fat-fed mice displayed enhanced apoptosis compared to controls (p <
.005). Furthermore, prostatic tissue demonstrated reduction in
epithelial folding, an effect which was significantly reversed after
MUFA diet administration. Our findings provide the basis for further
investigation of AGE-RAGE axis in testicular and prostatic disturbances
associated with diet-induced obesity. Simple dietetic intervention has
beneficial effects on metabolic dysfunction of reproductive system
before overt manifestations, indicating glycation as a promising
therapeutic target