Further evidence supporting a potential role for ADH1B in obesity

Abstract Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D...

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Autores principales: Liza D. Morales, Douglas T. Cromack, Devjit Tripathy, Marcel Fourcaudot, Satish Kumar, Joanne E. Curran, Melanie Carless, Harald H. H. Göring, Shirley L. Hu, Juan Carlos Lopez-Alvarenga, Kristina M. Garske, Päivi Pajukanta, Kerrin S. Small, Craig A. Glastonbury, Swapan K. Das, Carl Langefeld, Robert L. Hanson, Wen-Chi Hsueh, Luke Norton, Rector Arya, Srinivas Mummidi, John Blangero, Ralph A. DeFronzo, Ravindranath Duggirala, Christopher P. Jenkinson
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/1659f6d5d12d42ebbff7be8f7ccaf33e
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spelling oai:doaj.org-article:1659f6d5d12d42ebbff7be8f7ccaf33e2021-12-02T15:23:29ZFurther evidence supporting a potential role for ADH1B in obesity10.1038/s41598-020-80563-z2045-2322https://doaj.org/article/1659f6d5d12d42ebbff7be8f7ccaf33e2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80563-zhttps://doaj.org/toc/2045-2322Abstract Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D. We previously showed that gene expression of alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity and IR in subcutaneous adipose tissue of Mexican Americans. In the current study, a meta-analysis of the relationship between ADH1B expression and BMI in Mexican Americans, African Americans, Europeans, and Pima Indians verified that BMI was increased with decreased ADH1B expression. Using established human subcutaneous pre-adipocyte cell lines derived from lean (BMI < 30 kg m−2) or obese (BMI ≥ 30 kg m−2) donors, we found that ADH1B protein expression increased substantially during differentiation, and overexpression of ADH1B inhibited fatty acid binding protein expression. Mature adipocytes from lean donors expressed ADH1B at higher levels than obese donors. Insulin further induced ADH1B protein expression as well as enzyme activity. Knockdown of ADH1B expression decreased insulin-stimulated glucose uptake. Our findings suggest that ADH1B is involved in the proper development and metabolic activity of adipose tissues and this function is suppressed by obesity.Liza D. MoralesDouglas T. CromackDevjit TripathyMarcel FourcaudotSatish KumarJoanne E. CurranMelanie CarlessHarald H. H. GöringShirley L. HuJuan Carlos Lopez-AlvarengaKristina M. GarskePäivi PajukantaKerrin S. SmallCraig A. GlastonburySwapan K. DasCarl LangefeldRobert L. HansonWen-Chi HsuehLuke NortonRector AryaSrinivas MummidiJohn BlangeroRalph A. DeFronzoRavindranath DuggiralaChristopher P. JenkinsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Liza D. Morales
Douglas T. Cromack
Devjit Tripathy
Marcel Fourcaudot
Satish Kumar
Joanne E. Curran
Melanie Carless
Harald H. H. Göring
Shirley L. Hu
Juan Carlos Lopez-Alvarenga
Kristina M. Garske
Päivi Pajukanta
Kerrin S. Small
Craig A. Glastonbury
Swapan K. Das
Carl Langefeld
Robert L. Hanson
Wen-Chi Hsueh
Luke Norton
Rector Arya
Srinivas Mummidi
John Blangero
Ralph A. DeFronzo
Ravindranath Duggirala
Christopher P. Jenkinson
Further evidence supporting a potential role for ADH1B in obesity
description Abstract Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D. We previously showed that gene expression of alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity and IR in subcutaneous adipose tissue of Mexican Americans. In the current study, a meta-analysis of the relationship between ADH1B expression and BMI in Mexican Americans, African Americans, Europeans, and Pima Indians verified that BMI was increased with decreased ADH1B expression. Using established human subcutaneous pre-adipocyte cell lines derived from lean (BMI < 30 kg m−2) or obese (BMI ≥ 30 kg m−2) donors, we found that ADH1B protein expression increased substantially during differentiation, and overexpression of ADH1B inhibited fatty acid binding protein expression. Mature adipocytes from lean donors expressed ADH1B at higher levels than obese donors. Insulin further induced ADH1B protein expression as well as enzyme activity. Knockdown of ADH1B expression decreased insulin-stimulated glucose uptake. Our findings suggest that ADH1B is involved in the proper development and metabolic activity of adipose tissues and this function is suppressed by obesity.
format article
author Liza D. Morales
Douglas T. Cromack
Devjit Tripathy
Marcel Fourcaudot
Satish Kumar
Joanne E. Curran
Melanie Carless
Harald H. H. Göring
Shirley L. Hu
Juan Carlos Lopez-Alvarenga
Kristina M. Garske
Päivi Pajukanta
Kerrin S. Small
Craig A. Glastonbury
Swapan K. Das
Carl Langefeld
Robert L. Hanson
Wen-Chi Hsueh
Luke Norton
Rector Arya
Srinivas Mummidi
John Blangero
Ralph A. DeFronzo
Ravindranath Duggirala
Christopher P. Jenkinson
author_facet Liza D. Morales
Douglas T. Cromack
Devjit Tripathy
Marcel Fourcaudot
Satish Kumar
Joanne E. Curran
Melanie Carless
Harald H. H. Göring
Shirley L. Hu
Juan Carlos Lopez-Alvarenga
Kristina M. Garske
Päivi Pajukanta
Kerrin S. Small
Craig A. Glastonbury
Swapan K. Das
Carl Langefeld
Robert L. Hanson
Wen-Chi Hsueh
Luke Norton
Rector Arya
Srinivas Mummidi
John Blangero
Ralph A. DeFronzo
Ravindranath Duggirala
Christopher P. Jenkinson
author_sort Liza D. Morales
title Further evidence supporting a potential role for ADH1B in obesity
title_short Further evidence supporting a potential role for ADH1B in obesity
title_full Further evidence supporting a potential role for ADH1B in obesity
title_fullStr Further evidence supporting a potential role for ADH1B in obesity
title_full_unstemmed Further evidence supporting a potential role for ADH1B in obesity
title_sort further evidence supporting a potential role for adh1b in obesity
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/1659f6d5d12d42ebbff7be8f7ccaf33e
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