Metformin mitigates the impaired development of skeletal muscle in the offspring of obese mice

J. F. Tong, X. Yan, J. X. Zhao, M. J. Zhu, P. W. Nathanielsz, M. Du

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background: Maternal obesity is linked with offspring obesity and type 2 diabetes. Skeletal muscle (SM) insulin resistance is central to the development of diabetes. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is inhibited in SM of fetuses born to obese mothers.Objective: The aim of this study was to evaluate the effect of maternal metformin administration on AMPK activity and reversion of adverse changes in offspring SM of obese mice.Design: Female weanling C57BL/6J mice received either control diet (CON, 6 mice) or high-fat diet (HFD; OB, 12 mice) for 8 weeks before mating. After mating, mice continued receiving their respective CON or OB diets. In addition, 6 of those 12 mice fed with fat diet also received metformin administration (2 mg per ml in drinking water) throughout gestation and lactation (MET). After weaning at postnatal 21 days, offspring were fed a HFD to mimic a postnatal obesogenic environment until necropsy.Results: Mothers receiving the fat diet developed obesity. OB offspring showed higher adiposity than CON and MET offspring. AMPK phosphorylation was lower in SM of OB offspring. β-Catenin and myogenic regulatory factors, MyoD and myogenin, were downregulated in OB muscle, whereas the adipogenic marker, peroxisome proliferator-activated receptor-γ, was upregulated compared with CON muscle. Metformin administration prevented these changes in OB offspring SM. OB but not MET offspring demonstrated glucose intolerance. Mitochondrial content decreased, and activities of citrate synthase and β-hydroxyacyl-CoA dehydrogenase also decreased in OB offspring SM, whereas they were recovered in MET offspring SM.Conclusion: Maternal metformin administration improves SM development in OB offspring.

Original languageEnglish (US)
Article numbere7
JournalNutrition and Diabetes
Volume1
Issue number1
DOIs
StatePublished - 2011

Keywords

  • Amp-activated protein kinase
  • developmental programming
  • maternal obesity
  • metformin
  • skeletal muscle

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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