Impaired Lipolysis, Diminished Fat Oxidation, and Metabolic Inflexibility in Obese Girls With Polycystic Ovary Syndrome

• Published in: The journal of clinical endocrinology and metabolism 2018-02, Vol.103 (2), p.546-554
• Main Authors: Kim, Joon Young, Tfayli, Hala, Michaliszyn, Sara F, Arslanian, Silva
• Format: Article
• Language: English
• Subjects: Abdominal Fat - metabolism; Abdominal Fat - pathology; Adiponectin; Adipose tissue; Adolescent; Body Composition; Body fat; Body mass; Body mass index; Calorimetry; Carbohydrates; Case-Control Studies; Child; Clinical s; Fasting; Female; Flexibility; Glycerol; Humans; Hyperinsulinemia; Insulin; Insulin Resistance - physiology; Lipid Metabolism - physiology; Lipid peroxidation; Lipids; Lipolysis; Lipolysis - physiology; Metabolism; Obesity; Oxidation; Oxidation-Reduction; Pediatric Obesity - complications; Pediatric Obesity - metabolism; Phenotypes; Polycystic ovary syndrome; Polycystic Ovary Syndrome - complications; Polycystic Ovary Syndrome - metabolism; Respiratory quotient; Sex hormones; Substrates; Triglycerides
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2017-01958

Abstract Context Metabolic flexibility reflects the ability to switch from lipid to carbohydrate oxidation during insulin stimulation manifested in increased respiratory quotient (RQ). Little is known about adipose tissue metabolism and metabolic flexibility in adolescent girls with polycystic ovary syndrome (PCOS). Objective We investigated whole-body lipolysis, substrate oxidation, and metabolic flexibility in obese girls with PCOS vs obese girls without PCOS. Patients/Design Twenty-one obese girls with PCOS and 21 obese girls without PCOS were pair-matched for age and race. Body composition, abdominal visceral adipose tissue (VAT), sex hormones, lipid profile, and adiponectin were measured. Whole-body lipolysis ([2H5]glycerol turnover), RQ, and substrate oxidation (indirect calorimetry) were evaluated during fasting and a hyperinsulinemic-euglycemic clamp together with assessment of insulin sensitivity (IS). Results Despite similar body mass index and percent body fat, girls with PCOS vs girls without PCOS had lower fasting lipolysis and fat oxidation, less increase in RQ during hyperinsulinemia with impaired suppression in lipolysis and lipid oxidation, and lower IS. In multiple regression, the best predictors of metabolic flexibility were [using clinical parameters: adiponectin, fasting triglycerides, and insulin (R2 = 0.618, P < 0.0001); using research parameters: IS, VAT, and baseline RQ (R2 = 0.756, P < 0.0001)]. Conclusions Obese girls with PCOS vs obese girls without PCOS have decreased lipid mobilization, diminished fat oxidation, and metabolic inflexibility. Whether this metabolic phenotype of adipose tissue dysfunction, which is conducive to fat accretion, plays a role in the induction and maintenance of obesity in adolescent girls with PCOS remains to be determined. Obese girls with vs without PCOS have the inability to mobilize and burn fat from adipose stores in a fasting state and are metabolically inflexible during hyperinsulinemia to adjust to fuel supply.