title: Reproductive tissues maintain insulin sensitivity in diet-induced obesity.
abstract: Reproductive dysfunction is associated with obesity. We previously showed that female mice with diet-induced obesity (DIO) exhibit infertility and thus serve as a model of human polycystic ovary syndrome (PCOS). We postulated that differential insulin signaling of tissues leads to reproductive dysfunction; therefore, a comparison of insulin signaling in reproductive tissues and energy storage tissues was performed. Pituitary-specific insulin receptor knockout mice were used as controls. High-fat diet-induced stress, which leads to insulin resistance, was also investigated by assaying macrophage infiltration and phosphorylated Jun NH(2)-terminal kinase (pJNK) signaling. In lean mice, reproductive tissues exhibited reduced sensitivity to insulin compared with peripheral metabolic tissues. However, in obese mice, where metabolic tissues exhibited insulin resistance, the pituitary and ovary maintained insulin sensitivity. Pituitaries responded to insulin through insulin receptor substrate (IRS)2 but not IRS1, whereas in the ovary, both IRS1 and IRS2 were activated by insulin. Macrophage infiltration and pJNK signaling were not increased in the pituitary or ovary of lean mice relative to DIO mice. The lack of inflammation and cytokine signaling in the pituitary and ovary in DIO mice compared with lean mice may be one of the reasons that these tissues remained insulin sensitive. Retained sensitivity of the pituitary and ovary to insulin may contribute to the pathophysiology of PCOS.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. swu24@jhmi.edu
authors.forename: Sheng
authors.initials: S
authors.lastname: Wu
authors.forename: Sara
authors.initials: S
authors.lastname: Divall
authors.forename: Fredric
authors.initials: F
authors.lastname: Wondisford
authors.forename: Andrew
authors.initials: A
authors.lastname: Wolfe
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004032:Diet / Q000009:adverse effects; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D005835:Genitalia / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D008954:Models, Biological; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D012098:Reproduction / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007328:Insulin
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