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Sexual Dimorphism in Hepatic, Adipose Tissue, and Peripheral Tissue Insulin Sensitivity in Obese Humans

Glucose and lipid metabolism differ between men and women, and women tend to have better whole-body or muscle insulin sensitivity. This may be explained, in part, by differences in sex hormones and adipose tissue distribution. Few studies have investigated gender differences in hepatic, adipose tiss...

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Autores principales: ter Horst, Kasper W., Gilijamse, Pim W., de Weijer, Barbara A., Kilicarslan, Murat, Ackermans, Mariette T., Nederveen, Aart J., Nieuwdorp, Max, Romijn, Johannes A., Serlie, Mireille J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659894/
https://www.ncbi.nlm.nih.gov/pubmed/26635731
http://dx.doi.org/10.3389/fendo.2015.00182
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author ter Horst, Kasper W.
Gilijamse, Pim W.
de Weijer, Barbara A.
Kilicarslan, Murat
Ackermans, Mariette T.
Nederveen, Aart J.
Nieuwdorp, Max
Romijn, Johannes A.
Serlie, Mireille J.
author_facet ter Horst, Kasper W.
Gilijamse, Pim W.
de Weijer, Barbara A.
Kilicarslan, Murat
Ackermans, Mariette T.
Nederveen, Aart J.
Nieuwdorp, Max
Romijn, Johannes A.
Serlie, Mireille J.
author_sort ter Horst, Kasper W.
collection PubMed
description Glucose and lipid metabolism differ between men and women, and women tend to have better whole-body or muscle insulin sensitivity. This may be explained, in part, by differences in sex hormones and adipose tissue distribution. Few studies have investigated gender differences in hepatic, adipose tissue, and whole-body insulin sensitivity between severely obese men and women. In this study, we aimed to determine the differences in glucose metabolism between severely obese men and women using tissue-specific measurements of insulin sensitivity. Insulin sensitivity was compared between age and body mass index (BMI)-matched obese men and women by a two-step euglycemic hyperinsulinemic clamp with infusion of [6,6-(2)H(2)]glucose. Basal endogenous glucose production (EGP) and insulin sensitivity of the liver, adipose tissue, and peripheral tissues were assessed. Liver fat content was assessed by proton magnetic resonance spectroscopy in a subset of included subjects. We included 46 obese men and women (age, 48 ± 2 vs. 46 ± 2 years, p = 0.591; BMI, 41 ± 1 vs. 41 ± 1 kg/m(2), p = 0.832). There was no difference in basal EGP (14.4 ± 1.0 vs. 15.3 ± 0.5 μmol · kg fat-free mass(−1) · min(−1), p = 0.410), adipose tissue insulin sensitivity (insulin-mediated suppression of free fatty acids, 71.6 ± 3.6 vs. 76.1 ± 2.6%, p = 0.314), or peripheral insulin sensitivity (insulin-stimulated rate of disappearance of glucose, 26.2 ± 2.1 vs. 22.7 ± 1.7 μmol · kg(−1) · min(−1), p = 0.211). Obese men were characterized by lower hepatic insulin sensitivity (insulin-mediated suppression of EGP, 61.7 ± 4.1 vs. 72.8 ± 2.5% in men vs. women, respectively, p = 0.028). Finally, these observations could not be explained by differences in liver fat content (men vs. women, 16.5 ± 3.1 vs. 16.0 ± 2.5%, p = 0.913, n = 27). We conclude that obese men have lower hepatic, but comparable adipose tissue and peripheral tissue, insulin sensitivity compared to similarly obese women. Hepatic insulin resistance may contribute to the higher prevalence of diabetes in obese men. Further insight into the mechanisms underlying this gender difference may reveal novel targets for diabetes prevention and/or therapy.
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spelling pubmed-46598942015-12-03 Sexual Dimorphism in Hepatic, Adipose Tissue, and Peripheral Tissue Insulin Sensitivity in Obese Humans ter Horst, Kasper W. Gilijamse, Pim W. de Weijer, Barbara A. Kilicarslan, Murat Ackermans, Mariette T. Nederveen, Aart J. Nieuwdorp, Max Romijn, Johannes A. Serlie, Mireille J. Front Endocrinol (Lausanne) Endocrinology Glucose and lipid metabolism differ between men and women, and women tend to have better whole-body or muscle insulin sensitivity. This may be explained, in part, by differences in sex hormones and adipose tissue distribution. Few studies have investigated gender differences in hepatic, adipose tissue, and whole-body insulin sensitivity between severely obese men and women. In this study, we aimed to determine the differences in glucose metabolism between severely obese men and women using tissue-specific measurements of insulin sensitivity. Insulin sensitivity was compared between age and body mass index (BMI)-matched obese men and women by a two-step euglycemic hyperinsulinemic clamp with infusion of [6,6-(2)H(2)]glucose. Basal endogenous glucose production (EGP) and insulin sensitivity of the liver, adipose tissue, and peripheral tissues were assessed. Liver fat content was assessed by proton magnetic resonance spectroscopy in a subset of included subjects. We included 46 obese men and women (age, 48 ± 2 vs. 46 ± 2 years, p = 0.591; BMI, 41 ± 1 vs. 41 ± 1 kg/m(2), p = 0.832). There was no difference in basal EGP (14.4 ± 1.0 vs. 15.3 ± 0.5 μmol · kg fat-free mass(−1) · min(−1), p = 0.410), adipose tissue insulin sensitivity (insulin-mediated suppression of free fatty acids, 71.6 ± 3.6 vs. 76.1 ± 2.6%, p = 0.314), or peripheral insulin sensitivity (insulin-stimulated rate of disappearance of glucose, 26.2 ± 2.1 vs. 22.7 ± 1.7 μmol · kg(−1) · min(−1), p = 0.211). Obese men were characterized by lower hepatic insulin sensitivity (insulin-mediated suppression of EGP, 61.7 ± 4.1 vs. 72.8 ± 2.5% in men vs. women, respectively, p = 0.028). Finally, these observations could not be explained by differences in liver fat content (men vs. women, 16.5 ± 3.1 vs. 16.0 ± 2.5%, p = 0.913, n = 27). We conclude that obese men have lower hepatic, but comparable adipose tissue and peripheral tissue, insulin sensitivity compared to similarly obese women. Hepatic insulin resistance may contribute to the higher prevalence of diabetes in obese men. Further insight into the mechanisms underlying this gender difference may reveal novel targets for diabetes prevention and/or therapy. Frontiers Media S.A. 2015-11-26 /pmc/articles/PMC4659894/ /pubmed/26635731 http://dx.doi.org/10.3389/fendo.2015.00182 Text en Copyright © 2015 ter Horst, Gilijamse, de Weijer, Kilicarslan, Ackermans, Nederveen, Nieuwdorp, Romijn and Serlie. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
ter Horst, Kasper W.
Gilijamse, Pim W.
de Weijer, Barbara A.
Kilicarslan, Murat
Ackermans, Mariette T.
Nederveen, Aart J.
Nieuwdorp, Max
Romijn, Johannes A.
Serlie, Mireille J.
Sexual Dimorphism in Hepatic, Adipose Tissue, and Peripheral Tissue Insulin Sensitivity in Obese Humans
title Sexual Dimorphism in Hepatic, Adipose Tissue, and Peripheral Tissue Insulin Sensitivity in Obese Humans
title_full Sexual Dimorphism in Hepatic, Adipose Tissue, and Peripheral Tissue Insulin Sensitivity in Obese Humans
title_fullStr Sexual Dimorphism in Hepatic, Adipose Tissue, and Peripheral Tissue Insulin Sensitivity in Obese Humans
title_full_unstemmed Sexual Dimorphism in Hepatic, Adipose Tissue, and Peripheral Tissue Insulin Sensitivity in Obese Humans
title_short Sexual Dimorphism in Hepatic, Adipose Tissue, and Peripheral Tissue Insulin Sensitivity in Obese Humans
title_sort sexual dimorphism in hepatic, adipose tissue, and peripheral tissue insulin sensitivity in obese humans
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659894/
https://www.ncbi.nlm.nih.gov/pubmed/26635731
http://dx.doi.org/10.3389/fendo.2015.00182
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