title: Diet-induced obesity exacerbates metabolic and behavioral effects of polycystic ovary syndrome in a rodent model.
abstract: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Although a comorbidity of PCOS is obesity, many are lean. We hypothesized that increased saturated fat consumption and obesity would exacerbate metabolic and stress indices in a rodent model of PCOS. Female rats were implanted with the nonaromatizable androgen dihydrotestosterone (DHT) or placebo pellets prior to puberty. Half of each group was maintained ad libitum on either a high-fat diet (HFD; 40% butter fat calories) or nutrient-matched low-fat diet (LFD). Irrespective of diet, DHT-treated animals gained more body weight, had irregular cycles, and were glucose intolerant compared with controls on both diets. HFD/DHT animals had the highest levels of fat mass and insulin resistance. DHT animals demonstrated increased anxiety-related behavior in the elevated plus maze by decreased distance traveled and time in the open arms. HFD consumption increased immobility during the forced-swim test. DHT treatment suppressed diurnal corticosterone measurements in both diet groups. In parallel, DHT treatment significantly dampened stress responsivity to a mild stressor. Brains of DHT animals showed attenuated c-Fos activation in the ventromedial hypothalamus and arcuate nucleus; irrespective of DHT-treatment, however, all HFD animals had elevated hypothalamic paraventricular nucleus c-Fos activation. Whereas hyperandrogenism drives overall body weight gain, glucose intolerance, anxiety behaviors, and stress responsivity, HFD consumption exacerbates the effect of androgens on adiposity, insulin resistance, and depressive behaviors.
authors.affiliation: Department of Obstetrics and Gynecology, University of Cincinnati Medical Center, Cincinnati, Ohio; Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Ilana B
authors.initials: IB
authors.lastname: Ressler
authors.affiliation: Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi;
authors.forename: Bernadette E
authors.initials: BE
authors.lastname: Grayson
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio; and.
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Ulrich-Lai
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan seeleyrj@umich.edu.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004195:Disease Models, Animal; D002149:Energy Intake / Q000187:drug effects; D005260:Female; D018149:Glucose Intolerance / Q000150:complications / Q000378:metabolism / Q000523:psychology; D007333:Insulin Resistance / Q000502:physiology; D009765:Obesity / Q000150:complications* / Q000523:psychology*; D011085:Polycystic Ovary Syndrome / Q000209:etiology / Q000378:metabolism* / Q000523:psychology*; D051381:Rats; D020318:Rats, Long-Evans; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism
chemical_list: D013196:Dihydrotestosterone
keywords: anxiety; depression; lean; obesity; polycystic ovary syndrome