Objective: To investigate the relationship of early obesity to metabolic syndrome during sex hormonal imbalances in mutant female mice at different ages.
Research methods and procedures: Hormonal imbalances, accumulation and nature of adipose tissue, food intake, glucose tolerance, and expression of candidate genes and markers of inflammation were studied by comparing wild-type, null, and haploinsufficient follitropin receptor knockout female mice at different ages.
Results: Follitropin receptor deletion in mice produced null females that are infertile and haploinsufficient mice that undergo accelerated biological aging. Both types of mutants with sex hormonal imbalances have central obesity without hyperphagia, but circulating leptin is elevated. Adipocyte hyperplasia and hypertrophy is attributed to elevated peroxisome proliferator-activated receptor gamma expression. Adiponectin protein levels increase in fat tissue and plasma. Only mutants but not controls acquire age-dependent decline in glucose tolerance with high insulin and altered pancreatic beta cells. Changes in inflammation markers, decreased muscle insulin receptor phosphorylation, and increase of the enzyme protein tyrosine phosphatase 1B indicate insulin resistance.
Discussion: In this animal model, the chronological appearance of early obesity induced by hormonal imbalances culminates in characteristics that are attributable to metabolic syndrome, including cardiovascular abnormalities. Dissection of the depot-specific alterations and defining molecular interrelationships could help in developing targeted remedies and resolving complications and controversies related to health benefits and adversities of current hormone replacement therapy.