Diet-induced obesity exacerbates metabolic and behavioral effects of polycystic ovary syndrome in a rodent model
Autor: | Yvonne M. Ulrich-Lai, Randy J. Seeley, Ilana B. Ressler, Bernadette E. Grayson |
---|---|
Rok vydání: | 2015 |
Předmět: |
endocrine system
Elevated plus maze medicine.medical_specialty Physiology medicine.drug_class Endocrinology Diabetes and Metabolism Saturated fat Diet High-Fat Insulin resistance Physiology (medical) Internal medicine Glucose Intolerance Animals Medicine Rats Long-Evans Obesity Adiposity Behavior Animal business.industry Body Weight Hyperandrogenism Dihydrotestosterone Articles Androgen medicine.disease Polycystic ovary Rats Disease Models Animal Endocrinology Hypothalamus Female Insulin Resistance Energy Intake business Stress Psychological hormones hormone substitutes and hormone antagonists Polycystic Ovary Syndrome medicine.drug |
Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 308:E1076-E1084 |
ISSN: | 1522-1555 0193-1849 |
DOI: | 10.1152/ajpendo.00182.2014 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |