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Physiology

Response of skeletal muscle UCP2-expression during metabolic adaptation to caloric restriction

International Journal of Obesity volume 42, pages 974–984 (2018)Cite this article

Subjects

Abstract

Background/objectives

Spendthrift vs. thrifty individuals expend more energy and experience greater weight loss during caloric restriction (CR). Adaptive mechanisms in skeletal muscle, adipose tissue, and on hormone level modulate energy expenditure (EE) during weight loss. Metabolic mechanisms underlying the variability in EE during CR are unclear. The present study explored whether during long-term CR (i) gene expression changes in skeletal muscle and adipose tissue relate with the individual EE response and weight loss, and (ii) altered catecholamine and FGF21-concentrations are associated with measures of metabolic adaptation.

Subjects/methods

In a 10-week inpatient study, 24-h EE was measured before and after 6 weeks of 50% CR in 12 subjects using whole-room indirect calorimetry. Weight loss was assessed and repeated hormone measurements performed. Muscle and adipose tissue biopsies were taken before and after CR, and gene expression was assessed (RNA-Seq). Genes showing the most significant changes after CR were tested for association with EE and followed-up for further association with metabolic measures in a separate phenotyping study (n = 103).

Results

Muscle UCP2 showed the strongest change after CR (log2-fold change = −1.57, false discovery rate = 0.10) and was considered the best gene for exploration of metabolic adaptive processes. A greater decrease in UCP2-expression was associated with less weight loss (P = 0.03, r = 0.77) and relatively lower 24-h EE after CR (P = 0.001, r = −0.96). Post-CR changes in FGF21-plasma concentrations correlated with UCP2-expression change (P = 0.02, r = −0.89) and weight loss (P = 0.003, r = −0.83). In a separate metabolic phenotyping study, muscle UCP2-expression correlated with respiratory quotient and macronutrient oxidation. In adipose tissue, no candidate genes for metabolic exploration were found.

Conclusions

Changes in muscle UCP2-expression reflect an inter-individual metabolic response to long-term CR and may influence EE and weight loss via modulation of substrate oxidation.

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Acknowledgements

We thank all volunteers who participated in this study.

Funding

National Institutes of Health Intramural Research Fund.

Author information

Authors and Affiliations

  1. Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 4212 North 16th Street, Phoenix, AZ, 85016, USA

    Sascha Heinitz, Paolo Piaggi, Susan Bonfiglio, Jonathan Krakoff & Susanne B. Votruba

  2. Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, 1001S. McAllister Avenue, Tempe, AZ, 85287, USA

    Shanshan Yang & Jason Steel

Authors
  1. Sascha Heinitz
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  2. Paolo Piaggi
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Correspondence to Susanne B. Votruba.

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The authors declare that they have no conflict of interest.

Additional information

Clinical Trial Registration: NCT00687115, NCT00340132; clinicaltrials.gov

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Heinitz, S., Piaggi, P., Yang, S. et al. Response of skeletal muscle UCP2-expression during metabolic adaptation to caloric restriction. Int J Obes 42, 974–984 (2018). https://doi.org/10.1038/s41366-018-0085-2

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