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JCI Insight. 2017 Jul 20;2(14). doi: 10.1172/jci.insight.93367. eCollection 2017 Jul 20.

Red blood cell β-adrenergic receptors contribute to diet-induced energy expenditure by increasing O2 supply.

JCI insight

Eun Ran Kim, Shengjie Fan, Dmitry Akhmedov, Kaiqi Sun, Hoyong Lim, William O'Brien, Yuanzhong Xu, Leandra R Mangieri, Yaming Zhu, Cheng-Chi Lee, Yeonseok Chung, Yang Xia, Yong Xu, Feng Li, Kai Sun, Rebecca Berdeaux, Qingchun Tong

Affiliations

  1. Brown Foundation Institute of Molecular Medicine and University of Texas McGovern Medical School, Houston, Texas, USA.
  2. School of Pharmacy, Shanghai University of Chinese Traditional Medicine, Shanghai, China.
  3. Department of Integrative Biology and Pharmacology, Graduate Program in Cell and Regulatory Biology, Graduate School of Biomedical Sciences.
  4. Department of Biochemistry and Molecular Biology, Graduate Program in Biochemistry, and.
  5. Department of Neurobiology and Anatomy, Graduate Program in Neuroscience, Graduate School of Biological Sciences, University of Texas McGovern Medical School, Houston, Texas, USA.
  6. Children's Nutrition Research Center, Department of Pediatrics, and.
  7. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.

PMID: 28724789 PMCID: PMC5518553 DOI: 10.1172/jci.insight.93367

Abstract

Diet-induced obesity (DIO) represents the major cause for the current obesity epidemic, but the mechanism underlying DIO is unclear. β-Adrenergic receptors (β-ARs) play a major role in sympathetic nervous system-mediated (SNS-mediated) diet-induced energy expenditure (EE). Rbc express abundant β-ARs; however, a potential role for rbc in DIO remains untested. Here, we demonstrated that high-fat, high-caloric diet (HFD) feeding increased both EE and blood O2 content, and the HFD-induced increases in blood O2 level and in body weight gain were negatively correlated. Deficiency of β-ARs in rbc reduced glycolysis and ATP levels, diminished HFD-induced increases in both blood O2 content and EE, and resulted in DIO. Importantly, specific activation of cAMP signaling in rbc promoted HFD-induced EE and reduced HFD-induced tissue hypoxia independent of obesity. Both HFD and pharmacological activation cAMP signaling in rbc led to increased glycolysis and ATP levels. These results identify a previously unknown role for rbc β-ARs in mediating the SNS action on HFD-induced EE by increasing O2 supply, and they demonstrate that HFD-induced EE is limited by blood O2 availability and can be augenmented by increased O2 supply.

Keywords: Endocrinology; Metabolism

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