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Physiology

Insulin suppression of fatty acid skeletal muscle enzyme activity in postmenopausal women, and improvements in metabolic flexibility and lipoprotein lipase with aerobic exercise and weight loss

International Journal of Obesity volume 43, pages 276–284 (2019)Cite this article

Subjects

Abstract

Background

Obesity and insulin resistance are characterized by metabolic inflexibility, a condition described as an inability to switch from fat oxidation during fasting to carbohydrate oxidation during hyperinsulinemia. The purpose of this study was to examine predictors of metabolic flexibility in 103 obese (37–59% fat), sedentary (VO2max: 19.4 ± 0.5 ml/kg/min), postmenopausal (45–76 years) women, and changes in metabolic flexibility with exercise and weight loss interventions.

Methods

Insulin sensitivity (M) and metabolic flexibility via an 80 mU/m2/min hyperinsulinemic–euglycemic clamp, VO2max, and body composition were measured. Metabolic flexibility was measured after 6-months aerobic training + weight loss (AEX + WL: n = 43) or weight loss (WL: n = 31). Basal and insulin-stimulated vastus lateralis skeletal muscle samples were available from a subset of these women (n = 45).

Results

Metabolic flexibility correlated inversely with glucose120 min of OGTT, fasting insulin, and the percent change (insulin–basal) in lipoprotein lipase (LPL) activity and positively with M, but not with VO2max, total body fat, visceral fat, or subcutaneous abdominal fat. Skeletal muscle acyl-CoA synthase and citrate synthase activities decreased during hyperinsulinemia. Metabolic flexibility increased after AEX + WL but not WL, and the percent change in metabolic flexibility was inversely related to the percent change in insulin’s effect on LPL activity.

Conclusion

Metabolic flexibility is related to insulin sensitivity and insulin’s action on LPL. Furthermore, metabolic flexibility and insulin suppression of skeletal muscle LPL activity increase with AEX + WL in overweight and obese, sedentary older women.

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Acknowledgements

Our appreciation is extended to the women who participated in this study. We are grateful to Andrew P. Goldberg, M.D., the medical team, nurses, laboratory technicians, and exercise physiologists of the Division of Gerontology and Geriatric Medicine and GRECC, for their assistance to this project. This study was supported by VA Senior Research Career Scientist Award from the United States (U.S., Department of Veterans Affairs (Rehabilitation Research and Development Service) to AS Ryan, and resources of VA Medical Center Baltimore Geriatric Research, Education and Clinical Center (GRECC). This study was supported by NIH grants RO1-AG19310, R01 AG20116, P30-AG028747, and P30 DK072488.

Author contributions

ASR and HKO conceived of this research, performed the experiments, analyzed the data, and interpreted the results of the experiments; ASR drafted the manuscript; ASR and HKO edited and approved the manuscript.

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Authors and Affiliations

  1. VA Research Service, VA Maryland Health Care System, Baltimore, MD, 21201, USA

    Alice S. Ryan & Heidi K. Ortmeyer

  2. Department of Medicine, Division of Gerontology and Geriatric Medicine at the University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Alice S. Ryan & Heidi K. Ortmeyer

  3. Baltimore VA, GRECC, Baltimore, MD, 21201, USA

    Alice S. Ryan & Heidi K. Ortmeyer

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  1. Alice S. Ryan
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Correspondence to Alice S. Ryan.

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Ryan, A.S., Ortmeyer, H.K. Insulin suppression of fatty acid skeletal muscle enzyme activity in postmenopausal women, and improvements in metabolic flexibility and lipoprotein lipase with aerobic exercise and weight loss. Int J Obes 43, 276–284 (2019). https://doi.org/10.1038/s41366-018-0068-3

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