Red blood cell β-adrenergic receptors contribute to diet-induced energy expenditure by increasing O2 supply
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
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
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Research Article Endocrinology Metabolism

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

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.

Authors

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

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Figure 1

HFD feeding reversibly increases energy expenditure and blood O2 content.

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HFD feeding reversibly increases energy expenditure and blood O2 content...
(A) Correlation between blood O2 content and body weight measured in a cohort of C57 male mice (9–10 weeks old, n = 18). (B and C) Energy expenditure (B) and blood O2 content in a cohort of C57 male mice during chow high-fat, high-sucrose diet (HFD) transition (n = 10/group). (D–F) O2 consumption measured a cohort of C57 male mice first fed HFD from 8–18 weeks of age. Then, half of the mice were switched to chow and the other were kept on HFD. O2 consumption was measured during diet switch (D), and comparisons in O2 consumption (E) and O2 contents (F) 3 days before and 1 week after diet switch (n = 6/group) were measured. (G and H) A diagram showing the procedure for O2 content and body weight measurements in a cohort of C57 males reared on chow (9–10 weeks old, n = 17) and then fed HFD for 8 weeks (G), and correlation between net increases in body weight and those in blood O2 content by Parson’s correlation tests (H). L, light period; D, dark period. Dashed lines in B and G indicate dark periods. All data are presented as mean ± SEM; *P < 0.05, **P < 0.01 by paired student’s t tests (C), unpaired student’s t tests (F), or 2 way ANOVA tests with Tukey post-hoc analysis (E).