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Loss of voltage-gated proton channel Hv1 leads to diet-induced obesity in mice

OBJECTIVE: The voltage-gated proton channel Hv1 has been proposed to mediate NADPH oxidase (NOX) function by regulating intracellular pH during respiratory bursts. In our previous work, we showed that Hv1 is expressed in pancreatic β cells and positively regulates insulin secretion. Here, we investi...

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Autores principales: Pang, Huimin, Li, Jinwen, Du, Hongyan, Gao, Yingtang, Lv, Jili, Liu, Yanxia, Li, Shu Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039614/
https://www.ncbi.nlm.nih.gov/pubmed/32049639
http://dx.doi.org/10.1136/bmjdrc-2019-000951
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author Pang, Huimin
Li, Jinwen
Du, Hongyan
Gao, Yingtang
Lv, Jili
Liu, Yanxia
Li, Shu Jie
author_facet Pang, Huimin
Li, Jinwen
Du, Hongyan
Gao, Yingtang
Lv, Jili
Liu, Yanxia
Li, Shu Jie
author_sort Pang, Huimin
collection PubMed
description OBJECTIVE: The voltage-gated proton channel Hv1 has been proposed to mediate NADPH oxidase (NOX) function by regulating intracellular pH during respiratory bursts. In our previous work, we showed that Hv1 is expressed in pancreatic β cells and positively regulates insulin secretion. Here, we investigated the role of Hv1 in adipose tissue differentiation, metabolic homeostasis and insulin sensitivity using Hv1 knockout (KO) mice. DESIGN: Mice with genetic deletion of Hv1 are treated with high-fat diet (HFD) similar to wild-type (WT) mice. Body weight gain, adiposity, insulin sensitivity and gene expressions in both adipose tissue and liver were analyzed. RESULTS: Mice with genetic deletion of Hv1 display overt obesity with higher body weight gain and accumulation of adipose tissue compared with similarly HFD-treated WT. Hv1-deficient mice develop more glucose intolerance than WT, but no significant difference in insulin resistance, after fed with HFD. Deficiency of Hv1 results in a remarkable increase in epididymal adipocyte weight and size, while the gene expressions of proinflammatory factors and cytokines are obviously enhanced in the HFD-fed mice. Furthermore, the gene expression of Hv1 is increased in the HFD-fed mice, which is accompanied by the increase of NOX2 and NOX4. In addition, there is more severely diet-induced steatosis and inflammation in liver in KO mice. CONCLUSION: Our data demonstrated that lacking of Hv1 results in diet-induced obesity in mice through inflammation and hepatic steatosis. This study suggested that Hv1 acts as a positive regulator of metabolic homeostasis and a potential target for antiobesity drugs in therapy and may serve as an adaptive mechanism in cooperating with NOX to mediate reactive oxygen species for adipogenesis and insulin sensitivity.
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spelling pubmed-70396142020-03-03 Loss of voltage-gated proton channel Hv1 leads to diet-induced obesity in mice Pang, Huimin Li, Jinwen Du, Hongyan Gao, Yingtang Lv, Jili Liu, Yanxia Li, Shu Jie BMJ Open Diabetes Res Care Obesity Studies OBJECTIVE: The voltage-gated proton channel Hv1 has been proposed to mediate NADPH oxidase (NOX) function by regulating intracellular pH during respiratory bursts. In our previous work, we showed that Hv1 is expressed in pancreatic β cells and positively regulates insulin secretion. Here, we investigated the role of Hv1 in adipose tissue differentiation, metabolic homeostasis and insulin sensitivity using Hv1 knockout (KO) mice. DESIGN: Mice with genetic deletion of Hv1 are treated with high-fat diet (HFD) similar to wild-type (WT) mice. Body weight gain, adiposity, insulin sensitivity and gene expressions in both adipose tissue and liver were analyzed. RESULTS: Mice with genetic deletion of Hv1 display overt obesity with higher body weight gain and accumulation of adipose tissue compared with similarly HFD-treated WT. Hv1-deficient mice develop more glucose intolerance than WT, but no significant difference in insulin resistance, after fed with HFD. Deficiency of Hv1 results in a remarkable increase in epididymal adipocyte weight and size, while the gene expressions of proinflammatory factors and cytokines are obviously enhanced in the HFD-fed mice. Furthermore, the gene expression of Hv1 is increased in the HFD-fed mice, which is accompanied by the increase of NOX2 and NOX4. In addition, there is more severely diet-induced steatosis and inflammation in liver in KO mice. CONCLUSION: Our data demonstrated that lacking of Hv1 results in diet-induced obesity in mice through inflammation and hepatic steatosis. This study suggested that Hv1 acts as a positive regulator of metabolic homeostasis and a potential target for antiobesity drugs in therapy and may serve as an adaptive mechanism in cooperating with NOX to mediate reactive oxygen species for adipogenesis and insulin sensitivity. BMJ Publishing Group 2020-02-10 /pmc/articles/PMC7039614/ /pubmed/32049639 http://dx.doi.org/10.1136/bmjdrc-2019-000951 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Obesity Studies
Pang, Huimin
Li, Jinwen
Du, Hongyan
Gao, Yingtang
Lv, Jili
Liu, Yanxia
Li, Shu Jie
Loss of voltage-gated proton channel Hv1 leads to diet-induced obesity in mice
title Loss of voltage-gated proton channel Hv1 leads to diet-induced obesity in mice
title_full Loss of voltage-gated proton channel Hv1 leads to diet-induced obesity in mice
title_fullStr Loss of voltage-gated proton channel Hv1 leads to diet-induced obesity in mice
title_full_unstemmed Loss of voltage-gated proton channel Hv1 leads to diet-induced obesity in mice
title_short Loss of voltage-gated proton channel Hv1 leads to diet-induced obesity in mice
title_sort loss of voltage-gated proton channel hv1 leads to diet-induced obesity in mice
topic Obesity Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039614/
https://www.ncbi.nlm.nih.gov/pubmed/32049639
http://dx.doi.org/10.1136/bmjdrc-2019-000951
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