Sex specific effect of ATPase inhibitory factor 1 on body weight: studies in high fat diet induced obese mice and genetic association studies in humans
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kwak, So-Young | - |
dc.contributor.author | Chung, InHyeok | - |
dc.contributor.author | Kang, Joon | - |
dc.contributor.author | Perakakis, Nikolaos | - |
dc.contributor.author | Yoo, Eun Hye | - |
dc.contributor.author | Lee, Juhee | - |
dc.contributor.author | Jung, Hun Taek | - |
dc.contributor.author | Mun, Bo-Ram | - |
dc.contributor.author | Choi, Won-Seok | - |
dc.contributor.author | Kim, Oh Yoen | - |
dc.contributor.author | Kim, Seolsong | - |
dc.contributor.author | Kim, Eun-Kyoung | - |
dc.contributor.author | Oh, Hannah | - |
dc.contributor.author | Mantzoros, Christos S. | - |
dc.contributor.author | Chung, Ji Hyung | - |
dc.contributor.author | Kim, Hyeon Soo | - |
dc.contributor.author | Shin, Min-Jeong | - |
dc.date.accessioned | 2021-08-31T05:20:08Z | - |
dc.date.available | 2021-08-31T05:20:08Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2020-04 | - |
dc.identifier.issn | 0026-0495 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/56878 | - |
dc.description.abstract | Background: Based on the metabolic effect of exogenous ATPase inhibitory factor 1 (IF1) on glucose metabolism, we tested whether IF1 treatment is effective in ameliorating weight gain and whether its effects are sex specific. Methods: HFD-fed C57BL/6 mice were treated with IF1 (5mg/kg body weight, injected intraperitoneally). The underlying mechanisms of effect of IF1 on body weight were investigated in vitro and in vivo. Associations between genotypes of IF1 and obesity and relevant phenotype were further tested at the population level. Results: Chronic treatment with IF1 significantly decreased body weight gain by regulating food intake of HFD-fed male mice. IF1 activated the AKT/mTORC pathway and modulated the expression of appetite genes in the hypothalamus of HFD-fed male mice and its effect was confirmed in hypothalamic cell lines as well as hypothalamic primary cells. This required the interaction of IF1 with beta-F1-ATPase on the plasma membrane of hypothalamic cells, which led to an increase in extracellular ATP production. In addition, IF1 treatment showed sympathetic nerve activation as measured by serum norepinephrine levels and UCP-1 expression in the subcutaneous fat of HFD-fedmalemice. Notably, administration of recombinant IF1 to HFD-fed ovariectomized female mice showed remarkable reductions in food intake as well as body weight, which was not observed in wild-type 5-week female mice. Lastly, sex-specific genotype associations of IF1 with obesity prevalence and metabolic traits were demonstrated at the population level in humans. IF1 genetic variant (rs3767303) was significantly associated with lower prevalence of obesity and lower levels of body mass index, waist circumference, hemoglobin A(1c), and glucose response area only in male participants. Conclusion: IF1 is involved in weight regulation by controlling food intake and potentially sympathetic nerve activation in a sex-specific manner. (C) 2020 Elsevier Inc. All rights reserved. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | W B SAUNDERS CO-ELSEVIER INC | - |
dc.subject | ENERGY-BALANCE | - |
dc.subject | FOOD-INTAKE | - |
dc.subject | PROTEIN | - |
dc.subject | SYNTHASE | - |
dc.subject | MECHANISMS | - |
dc.subject | MYOKINES | - |
dc.subject | LEPTIN | - |
dc.subject | FOXO1 | - |
dc.subject | TOR | - |
dc.title | Sex specific effect of ATPase inhibitory factor 1 on body weight: studies in high fat diet induced obese mice and genetic association studies in humans | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Oh, Hannah | - |
dc.contributor.affiliatedAuthor | Kim, Hyeon Soo | - |
dc.contributor.affiliatedAuthor | Shin, Min-Jeong | - |
dc.identifier.doi | 10.1016/j.metabol.2020.154171 | - |
dc.identifier.scopusid | 2-s2.0-85078818468 | - |
dc.identifier.wosid | 000523185800010 | - |
dc.identifier.bibliographicCitation | METABOLISM-CLINICAL AND EXPERIMENTAL, v.105 | - |
dc.relation.isPartOf | METABOLISM-CLINICAL AND EXPERIMENTAL | - |
dc.citation.title | METABOLISM-CLINICAL AND EXPERIMENTAL | - |
dc.citation.volume | 105 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Endocrinology & Metabolism | - |
dc.relation.journalWebOfScienceCategory | Endocrinology & Metabolism | - |
dc.subject.keywordPlus | ENERGY-BALANCE | - |
dc.subject.keywordPlus | FOOD-INTAKE | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | SYNTHASE | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | MYOKINES | - |
dc.subject.keywordPlus | LEPTIN | - |
dc.subject.keywordPlus | FOXO1 | - |
dc.subject.keywordPlus | TOR | - |
dc.subject.keywordAuthor | ATPase inhibitory factor 1 | - |
dc.subject.keywordAuthor | Obesity | - |
dc.subject.keywordAuthor | Hypothalamus | - |
dc.subject.keywordAuthor | mTORC | - |
dc.subject.keywordAuthor | beta-F1-ATPase | - |
dc.subject.keywordAuthor | Akt | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
145 Anam-ro, Seongbuk-gu, Seoul, 02841, Korea+82-2-3290-2963
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.