Decreased Mitochondrial Dynamics Is Associated with Insulin Resistance, Metabolic Rate, and Fitness in African Americans
Abstract Context African American women (AAW) have a higher incidence of insulin resistance and are at a greater risk for the development of obesity and type 2 diabetes than Caucasian women (CW). Although several factors have been proposed to mediate these racial disparities, the mechanisms remain p...
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creator | Dubé, John J Collyer, Michael L Trant, Sara Toledo, Frederico G S Goodpaster, Bret H Kershaw, Erin E DeLany, James P |
description | Abstract
Context
African American women (AAW) have a higher incidence of insulin resistance and are at a greater risk for the development of obesity and type 2 diabetes than Caucasian women (CW). Although several factors have been proposed to mediate these racial disparities, the mechanisms remain poorly defined. We previously demonstrated that sedentary lean AAW have lower peripheral insulin sensitivity, reduced maximal aerobic fitness (VO2max), and lower resting metabolic rate (RMR) than CW. We have also demonstrated that skeletal muscle mitochondrial respiration is lower in AAW and appears to play a role in these racial differences.
Objective
The goal of this study was to assess mitochondrial pathways and dynamics to examine the potential mechanisms of lower insulin sensitivity, RMR, VO2max, and mitochondrial capacity in AAW.
Design
To achieve this goal, we assessed several mitochondrial pathways in skeletal muscle using gene array technology and semiquantitative protein analysis.
Results
We report alterations in mitochondrial pathways associated with inner membrane small molecule transport genes, fusion–fission, and autophagy in lean AAW. These differences were associated with lower insulin sensitivity, RMR, and VO2max.
Conclusions
Together these data suggest that the metabolic racial disparity of insulin resistance, RMR, VO2max, and mitochondrial capacity may be mediated by perturbations in mitochondrial pathways associated with membrane transport, fission–fusion, and autophagy. The mechanisms contributing to these differences remain unknown. |
doi_str_mv | 10.1210/clinem/dgz272 |
format | Article |
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Context
African American women (AAW) have a higher incidence of insulin resistance and are at a greater risk for the development of obesity and type 2 diabetes than Caucasian women (CW). Although several factors have been proposed to mediate these racial disparities, the mechanisms remain poorly defined. We previously demonstrated that sedentary lean AAW have lower peripheral insulin sensitivity, reduced maximal aerobic fitness (VO2max), and lower resting metabolic rate (RMR) than CW. We have also demonstrated that skeletal muscle mitochondrial respiration is lower in AAW and appears to play a role in these racial differences.
Objective
The goal of this study was to assess mitochondrial pathways and dynamics to examine the potential mechanisms of lower insulin sensitivity, RMR, VO2max, and mitochondrial capacity in AAW.
Design
To achieve this goal, we assessed several mitochondrial pathways in skeletal muscle using gene array technology and semiquantitative protein analysis.
Results
We report alterations in mitochondrial pathways associated with inner membrane small molecule transport genes, fusion–fission, and autophagy in lean AAW. These differences were associated with lower insulin sensitivity, RMR, and VO2max.
Conclusions
Together these data suggest that the metabolic racial disparity of insulin resistance, RMR, VO2max, and mitochondrial capacity may be mediated by perturbations in mitochondrial pathways associated with membrane transport, fission–fusion, and autophagy. The mechanisms contributing to these differences remain unknown.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/clinem/dgz272</identifier><identifier>PMID: 31833547</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adolescent ; Adult ; African American women ; Autophagy ; Basal Metabolism ; Cardiorespiratory fitness ; Clinical s ; Demographic aspects ; Development and progression ; Diabetes mellitus (non-insulin dependent) ; Exercise ; Female ; Follow-Up Studies ; Genetic aspects ; Health aspects ; Humans ; Insulin ; Insulin Resistance ; Male ; Membrane fusion ; Metabolic rate ; Metabolic regulation ; Metabolism ; Mitochondria ; Mitochondria - metabolism ; Mitochondria - pathology ; Mitochondrial Dynamics ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - pathology ; Musculoskeletal system ; Phagocytosis ; Physical fitness ; Prognosis ; Protein arrays ; Skeletal muscle ; Young Adult</subject><ispartof>The journal of clinical endocrinology and metabolism, 2020-04, Vol.105 (4), p.1210-1220</ispartof><rights>Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2019</rights><rights>Copyright © Oxford University Press 2015</rights><rights>Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2020 Oxford University Press</rights><rights>Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5572-7e0084f724cd4dbc95c22dd357044714d8d1d44488ae23e43465164a663ad733</citedby><cites>FETCH-LOGICAL-c5572-7e0084f724cd4dbc95c22dd357044714d8d1d44488ae23e43465164a663ad733</cites><orcidid>0000-0003-0366-3849 ; 0000-0002-0703-5930 ; 0000-0002-3887-4868</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2431029935?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,780,784,885,21388,21389,27924,27925,33530,33531,33744,33745,43659,43805,64385,64387,64389,72469,73123,73128,73129,73131</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31833547$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dubé, John J</creatorcontrib><creatorcontrib>Collyer, Michael L</creatorcontrib><creatorcontrib>Trant, Sara</creatorcontrib><creatorcontrib>Toledo, Frederico G S</creatorcontrib><creatorcontrib>Goodpaster, Bret H</creatorcontrib><creatorcontrib>Kershaw, Erin E</creatorcontrib><creatorcontrib>DeLany, James P</creatorcontrib><title>Decreased Mitochondrial Dynamics Is Associated with Insulin Resistance, Metabolic Rate, and Fitness in African Americans</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Abstract
Context
African American women (AAW) have a higher incidence of insulin resistance and are at a greater risk for the development of obesity and type 2 diabetes than Caucasian women (CW). Although several factors have been proposed to mediate these racial disparities, the mechanisms remain poorly defined. We previously demonstrated that sedentary lean AAW have lower peripheral insulin sensitivity, reduced maximal aerobic fitness (VO2max), and lower resting metabolic rate (RMR) than CW. We have also demonstrated that skeletal muscle mitochondrial respiration is lower in AAW and appears to play a role in these racial differences.
Objective
The goal of this study was to assess mitochondrial pathways and dynamics to examine the potential mechanisms of lower insulin sensitivity, RMR, VO2max, and mitochondrial capacity in AAW.
Design
To achieve this goal, we assessed several mitochondrial pathways in skeletal muscle using gene array technology and semiquantitative protein analysis.
Results
We report alterations in mitochondrial pathways associated with inner membrane small molecule transport genes, fusion–fission, and autophagy in lean AAW. These differences were associated with lower insulin sensitivity, RMR, and VO2max.
Conclusions
Together these data suggest that the metabolic racial disparity of insulin resistance, RMR, VO2max, and mitochondrial capacity may be mediated by perturbations in mitochondrial pathways associated with membrane transport, fission–fusion, and autophagy. The mechanisms contributing to these differences remain unknown.</description><subject>Adolescent</subject><subject>Adult</subject><subject>African American women</subject><subject>Autophagy</subject><subject>Basal Metabolism</subject><subject>Cardiorespiratory fitness</subject><subject>Clinical s</subject><subject>Demographic aspects</subject><subject>Development and progression</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Exercise</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Male</subject><subject>Membrane fusion</subject><subject>Metabolic rate</subject><subject>Metabolic regulation</subject><subject>Metabolism</subject><subject>Mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - pathology</subject><subject>Mitochondrial Dynamics</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - pathology</subject><subject>Musculoskeletal system</subject><subject>Phagocytosis</subject><subject>Physical fitness</subject><subject>Prognosis</subject><subject>Protein arrays</subject><subject>Skeletal muscle</subject><subject>Young Adult</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkk1vEzEQhlcIRNPCkSuyxKWHbuvPdfaCFPUDIrVCqnrgZjn2bOLitYO9Syi_HpeEQhEI-TCW_cw7nvFbVa8IPiaU4BPjXYD-xC6_UUmfVBPSclFL0sqn1QRjSupW0o971X7OtxgTzgV7Xu0xMmVMcDmpvp6BSaAzWHTlhmhWMdjktEdnd0H3zmQ0z2iWczRODwXauGGF5iGPpSy6huzyoIOBI3QFg15E7wy6LuAR0sGiCzcEyBkVdNYlZ3SJPfzY5BfVs077DC938aC6uTi_OX1fX354Nz-dXdZGCElrCRhPeScpN5bbhWmFodRaJiTmXBJup5ZYzvl0qoEy4Iw3gjRcNw3TVjJ2UL3dyq7HRQ_WQBiS9mqdXK_TnYraqcc3wa3UMn5REjdSCFoEDncCKX4eIQ-qd9mA9zpAHLOijEmMccObgr75A72NYwqlO0U5I5i2LRO_qKX2oFzoYqlr7kXVrOG0vB7jtlDHf6HKslB-JQboXDl_lFBvE0yKOSfoHnokWN07RW2dorZOKfzr3wfzQP-0RgHIFthEP0DKn_y4gaRWoP2w-qfoblhxXP-n_nf0TNmt</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Dubé, John J</creator><creator>Collyer, Michael L</creator><creator>Trant, Sara</creator><creator>Toledo, Frederico G S</creator><creator>Goodpaster, Bret H</creator><creator>Kershaw, Erin E</creator><creator>DeLany, James P</creator><general>Oxford University Press</general><general>Copyright Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0366-3849</orcidid><orcidid>https://orcid.org/0000-0002-0703-5930</orcidid><orcidid>https://orcid.org/0000-0002-3887-4868</orcidid></search><sort><creationdate>20200401</creationdate><title>Decreased Mitochondrial Dynamics Is Associated with Insulin Resistance, Metabolic Rate, and Fitness in African Americans</title><author>Dubé, John J ; Collyer, Michael L ; Trant, Sara ; Toledo, Frederico G S ; Goodpaster, Bret H ; Kershaw, Erin E ; DeLany, James P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5572-7e0084f724cd4dbc95c22dd357044714d8d1d44488ae23e43465164a663ad733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>African American women</topic><topic>Autophagy</topic><topic>Basal Metabolism</topic><topic>Cardiorespiratory fitness</topic><topic>Clinical s</topic><topic>Demographic aspects</topic><topic>Development and progression</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Exercise</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Male</topic><topic>Membrane fusion</topic><topic>Metabolic rate</topic><topic>Metabolic regulation</topic><topic>Metabolism</topic><topic>Mitochondria</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - pathology</topic><topic>Mitochondrial Dynamics</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - pathology</topic><topic>Musculoskeletal system</topic><topic>Phagocytosis</topic><topic>Physical fitness</topic><topic>Prognosis</topic><topic>Protein arrays</topic><topic>Skeletal muscle</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dubé, John J</creatorcontrib><creatorcontrib>Collyer, Michael L</creatorcontrib><creatorcontrib>Trant, Sara</creatorcontrib><creatorcontrib>Toledo, Frederico G S</creatorcontrib><creatorcontrib>Goodpaster, Bret H</creatorcontrib><creatorcontrib>Kershaw, Erin E</creatorcontrib><creatorcontrib>DeLany, James P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dubé, John J</au><au>Collyer, Michael L</au><au>Trant, Sara</au><au>Toledo, Frederico G S</au><au>Goodpaster, Bret H</au><au>Kershaw, Erin E</au><au>DeLany, James P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased Mitochondrial Dynamics Is Associated with Insulin Resistance, Metabolic Rate, and Fitness in African Americans</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>105</volume><issue>4</issue><spage>1210</spage><epage>1220</epage><pages>1210-1220</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>Abstract
Context
African American women (AAW) have a higher incidence of insulin resistance and are at a greater risk for the development of obesity and type 2 diabetes than Caucasian women (CW). Although several factors have been proposed to mediate these racial disparities, the mechanisms remain poorly defined. We previously demonstrated that sedentary lean AAW have lower peripheral insulin sensitivity, reduced maximal aerobic fitness (VO2max), and lower resting metabolic rate (RMR) than CW. We have also demonstrated that skeletal muscle mitochondrial respiration is lower in AAW and appears to play a role in these racial differences.
Objective
The goal of this study was to assess mitochondrial pathways and dynamics to examine the potential mechanisms of lower insulin sensitivity, RMR, VO2max, and mitochondrial capacity in AAW.
Design
To achieve this goal, we assessed several mitochondrial pathways in skeletal muscle using gene array technology and semiquantitative protein analysis.
Results
We report alterations in mitochondrial pathways associated with inner membrane small molecule transport genes, fusion–fission, and autophagy in lean AAW. These differences were associated with lower insulin sensitivity, RMR, and VO2max.
Conclusions
Together these data suggest that the metabolic racial disparity of insulin resistance, RMR, VO2max, and mitochondrial capacity may be mediated by perturbations in mitochondrial pathways associated with membrane transport, fission–fusion, and autophagy. The mechanisms contributing to these differences remain unknown.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>31833547</pmid><doi>10.1210/clinem/dgz272</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-0366-3849</orcidid><orcidid>https://orcid.org/0000-0002-0703-5930</orcidid><orcidid>https://orcid.org/0000-0002-3887-4868</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult African American women Autophagy Basal Metabolism Cardiorespiratory fitness Clinical s Demographic aspects Development and progression Diabetes mellitus (non-insulin dependent) Exercise Female Follow-Up Studies Genetic aspects Health aspects Humans Insulin Insulin Resistance Male Membrane fusion Metabolic rate Metabolic regulation Metabolism Mitochondria Mitochondria - metabolism Mitochondria - pathology Mitochondrial Dynamics Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Musculoskeletal system Phagocytosis Physical fitness Prognosis Protein arrays Skeletal muscle Young Adult |
title | Decreased Mitochondrial Dynamics Is Associated with Insulin Resistance, Metabolic Rate, and Fitness in African Americans |
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