Reproductive axis function and gonadotropin microheterogeneity in a male rat model of diet-induced obesity.
Obesity causes complex metabolic and endocrine changes that may lead to adverse outcomes, including hypogonadism. We herein studied the reproductive axis function in male rats under a high-fat diet and analyzed the impact of changes in glycosylation of pituitary LH on the bioactivity of this gonadotropin. Rats were fed with a diet enriched in saturated fat (20% of total calories) and euthanized on days 90 or 180 of diet. Long-term (180 days), high-fat feeding rats exhibited a metabolic profile compatible with insulin resistance and metabolic syndrome; they concomitantly showed decreased intrapituitary and serum LH concentrations, low serum testosterone levels, and elevated serum 17beta-estradiol concentrations. A fall in biological to immunological ratio of intrapituitary LH was detected in 180 days control diet-treated rats but not in high-fat-fed animals, as assessed by a homologous in vitro bioassay. Chromatofocusing of pituitary extracts yielded multiple LH charge isoforms; a trend towards decreased abundance of more basic isoforms (pH 9.99-9.0) was apparent in rats fed with the control diet for 180 days but not in those that were fed the diet enriched in saturated fat. It is concluded that long-term high-fat feeding alters the function of the pituitary-testicular axis, resulting in hypogonadotropic hypogonadism. The alterations in LH function found in these animals might be subserved by changes in hypothalamic GnRH output and/or sustained gonadotrope exposure to an altered sex steroid hormone milieu, representing a distinctly different regulatory mechanism whereby the pituitary attempts to counterbalance the effects of long-term obesity on reproductive function.
Olivares
Aleida
A
Research Unit in Reproductive Medicine, Hospital de Ginecobstetricia Luis Castelazo Ayala, IMSS, México D.F., Mexico. cristina.olivaress@imss.gob.mx
Méndez
Juan Pablo
JP
Zambrano
Elena
E
Cárdenas
Mario
M
Tovar
Armando
A
Perera-Marín
Gerardo
G
Ulloa-Aguirre
Alfredo
A
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004958:Estradiol / Q000097:blood; D006031:Glycosylation; D006863:Hydrogen-Ion Concentration; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D007986:Luteinizing Hormone / Q000032:analysis* / Q000097:blood / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome; D009765:Obesity / Q000209:etiology* / Q000503:physiopathology*; D010903:Pituitary Gland, Anterior / Q000737:chemistry; D020033:Protein Isoforms / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000502:physiology*; D013739:Testosterone / Q000097:blood; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004041:Dietary Fats; D020738:Leptin; D020033:Protein Isoforms; D014280:Triglycerides; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone