Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1783500836898340864 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7039614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT panghuimin lossofvoltagegatedprotonchannelhv1leadstodietinducedobesityinmice AT lijinwen lossofvoltagegatedprotonchannelhv1leadstodietinducedobesityinmice AT duhongyan lossofvoltagegatedprotonchannelhv1leadstodietinducedobesityinmice AT gaoyingtang lossofvoltagegatedprotonchannelhv1leadstodietinducedobesityinmice AT lvjili lossofvoltagegatedprotonchannelhv1leadstodietinducedobesityinmice AT liuyanxia lossofvoltagegatedprotonchannelhv1leadstodietinducedobesityinmice AT lishujie lossofvoltagegatedprotonchannelhv1leadstodietinducedobesityinmice |