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Declining muscle NAD+ in a hyperandrogenism PCOS mouse model: Possible role in metabolic dysregulation.
Aflatounian, Ali; Paris, Valentina Rodriguez; Richani, Dulama; Edwards, Melissa C; Cochran, Blake J; Ledger, William L; Gilchrist, Robert B; Bertoldo, Michael J; Wu, Lindsay E; Walters, Kirsty A.
Affiliation
  • Aflatounian A; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales, Sydney, NSW 2052, Australia.
  • Paris VR; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales, Sydney, NSW 2052, Australia.
  • Richani D; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales, Sydney, NSW 2052, Australia.
  • Edwards MC; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales, Sydney, NSW 2052, Australia.
  • Cochran BJ; School of Medical Sciences, University of New South Wales Sydney, Sydney, NSW 2052, Australia.
  • Ledger WL; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales, Sydney, NSW 2052, Australia.
  • Gilchrist RB; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales, Sydney, NSW 2052, Australia.
  • Bertoldo MJ; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales, Sydney, NSW 2052, Australia; School of Medical Sciences, University of New South Wales Sydney, Sydney, NSW 2052, Australia.
  • Wu LE; School of Medical Sciences, University of New South Wales Sydney, Sydney, NSW 2052, Australia. Electronic address: lindsay.wu@unsw.edu.au.
  • Walters KA; Fertility and Research Centre, School of Women's & Children's Health, University of New South Wales, Sydney, NSW 2052, Australia.
Mol Metab ; 65: 101583, 2022 11.
Article in En | MEDLINE | ID: mdl-36096453
Polycystic ovary syndrome (PCOS) is a common endocrine disorder, defined by reproductive and endocrine abnormalities, with metabolic dysregulation including obesity, insulin resistance and hepatic steatosis. Recently, it was found that skeletal muscle insulin sensitivity could be improved in obese, post-menopausal, pre-diabetic women through treatment with nicotinamide mononucleotide (NMN), a precursor to the prominent redox cofactor nicotinamide adenine dinucleotide (NAD+). Given that PCOS patients have a similar endocrine profile to these patients, we hypothesised that declining NAD levels in muscle might play a role in the pathogenesis of the metabolic syndrome associated with PCOS, and that this could be normalized through NMN treatment. Here, we tested the impact of NMN treatment on the metabolic syndrome of the dihydrotestosterone (DHT) induced mouse model of PCOS. We observed lower NAD levels in the muscle of PCOS mice, which was normalized by NMN treatment. PCOS mice were hyperinsulinaemic, resulting in increased adiposity and hepatic lipid deposition. Strikingly, NMN treatment completely normalized these aspects of metabolic dysfunction. We propose that addressing the decline in skeletal muscle NAD levels associated with PCOS can normalize insulin sensitivity, preventing compensatory hyperinsulinaemia, which drives obesity and hepatic lipid deposition, though we cannot discount an impact of NMN on other tissues to mediate these effects. These findings support further investigation into NMN treatment as a new therapy for normalizing the aberrant metabolic features of PCOS.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polycystic Ovary Syndrome / Insulin Resistance / Hyperandrogenism / Metabolic Syndrome Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Mol Metab Year: 2022 Document type: Article Affiliation country: Australia Country of publication: Germany

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polycystic Ovary Syndrome / Insulin Resistance / Hyperandrogenism / Metabolic Syndrome Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Mol Metab Year: 2022 Document type: Article Affiliation country: Australia Country of publication: Germany