Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone
ObjectiveRecent studies have indicated that serum testosterone in aging men is associated with insulin sensitivity and expression of genes involved in oxidative phosphorylation (OxPhos), and that testosterone treatment increases lipid oxidation. Herein, we investigated the effect of testosterone the...
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| Veröffentlicht in: | European journal of endocrinology 2014-07, Vol.171 (1), p.77-88 |
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| creator | Petersson, Stine J Christensen, Louise L Kristensen, Jonas M Kruse, Rikke Andersen, Marianne Højlund, Kurt |
| description | ObjectiveRecent studies have indicated that serum testosterone in aging men is associated with insulin sensitivity and expression of genes involved in oxidative phosphorylation (OxPhos), and that testosterone treatment increases lipid oxidation. Herein, we investigated the effect of testosterone therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels.MethodsSkeletal muscle biopsies were obtained before and after treatment with either testosterone gel (n=12) or placebo (n=13) for 6 months. Insulin sensitivity and substrate oxidation were assessed by euglycemic–hyperinsulinemic clamp and indirect calorimetry. Muscle mRNA levels and protein abundance and phosphorylation of enzymes involved in mitochondrial biogenesis, OxPhos, and lipid metabolism were examined by quantitative real-time PCR and western blotting.ResultsDespite an increase in lipid oxidation (P |
| doi_str_mv | 10.1530/EJE-14-0006 |
| format | Article |
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Herein, we investigated the effect of testosterone therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels.MethodsSkeletal muscle biopsies were obtained before and after treatment with either testosterone gel (n=12) or placebo (n=13) for 6 months. Insulin sensitivity and substrate oxidation were assessed by euglycemic–hyperinsulinemic clamp and indirect calorimetry. Muscle mRNA levels and protein abundance and phosphorylation of enzymes involved in mitochondrial biogenesis, OxPhos, and lipid metabolism were examined by quantitative real-time PCR and western blotting.ResultsDespite an increase in lipid oxidation (P<0.05), testosterone therapy had no effect on insulin sensitivity or mRNA levels of genes involved in mitochondrial biogenesis (PPARGC1A, PRKAA2, and PRKAG3), OxPhos (NDUFS1, ETFA, SDHA, UQCRC1, and COX5B), or lipid metabolism (ACADVL, CD36, CPT1B, HADH, and PDK4). Consistently, protein abundance of OxPhos subunits encoded by both nuclear (SDHA and UQCRC1) and mitochondrial DNA (ND6) and protein abundance and phosphorylation of AMP-activated protein kinase and p38 MAPK were unaffected by testosterone therapy.ConclusionThe beneficial effect of testosterone treatment on lipid oxidation is not explained by increased abundance or phosphorylation-dependent activity of enzymes known to regulate mitochondrial biogenesis or markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels.</description><identifier>ISSN: 0804-4643</identifier><identifier>EISSN: 1479-683X</identifier><identifier>DOI: 10.1530/EJE-14-0006</identifier><identifier>PMID: 24760536</identifier><language>eng</language><publisher>Bristol: Bioscientifica Ltd</publisher><subject>Aging - physiology ; Biological and medical sciences ; Blotting, Western ; Body Composition - drug effects ; Body Composition - physiology ; Clinical Study ; Electrophoresis, Polyacrylamide Gel ; Endocrinopathies ; Fundamental and applied biological sciences. Psychology ; Lipid Metabolism - physiology ; Medical sciences ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Oxidative Phosphorylation - drug effects ; Real-Time Polymerase Chain Reaction ; Testosterone - pharmacology ; Vertebrates: endocrinology</subject><ispartof>European journal of endocrinology, 2014-07, Vol.171 (1), p.77-88</ispartof><rights>2014 European Society of Endocrinology</rights><rights>2015 INIST-CNRS</rights><rights>2014 European Society of Endocrinology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b398t-d35d5cee72819f859e5a0052a886c03eb6a448111c8c6fe4e08ece2769fea8073</citedby><cites>FETCH-LOGICAL-b398t-d35d5cee72819f859e5a0052a886c03eb6a448111c8c6fe4e08ece2769fea8073</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28696529$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24760536$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Petersson, Stine J</creatorcontrib><creatorcontrib>Christensen, Louise L</creatorcontrib><creatorcontrib>Kristensen, Jonas M</creatorcontrib><creatorcontrib>Kruse, Rikke</creatorcontrib><creatorcontrib>Andersen, Marianne</creatorcontrib><creatorcontrib>Højlund, Kurt</creatorcontrib><title>Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone</title><title>European journal of endocrinology</title><addtitle>Eur J Endocrinol</addtitle><description>ObjectiveRecent studies have indicated that serum testosterone in aging men is associated with insulin sensitivity and expression of genes involved in oxidative phosphorylation (OxPhos), and that testosterone treatment increases lipid oxidation. Herein, we investigated the effect of testosterone therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels.MethodsSkeletal muscle biopsies were obtained before and after treatment with either testosterone gel (n=12) or placebo (n=13) for 6 months. Insulin sensitivity and substrate oxidation were assessed by euglycemic–hyperinsulinemic clamp and indirect calorimetry. Muscle mRNA levels and protein abundance and phosphorylation of enzymes involved in mitochondrial biogenesis, OxPhos, and lipid metabolism were examined by quantitative real-time PCR and western blotting.ResultsDespite an increase in lipid oxidation (P<0.05), testosterone therapy had no effect on insulin sensitivity or mRNA levels of genes involved in mitochondrial biogenesis (PPARGC1A, PRKAA2, and PRKAG3), OxPhos (NDUFS1, ETFA, SDHA, UQCRC1, and COX5B), or lipid metabolism (ACADVL, CD36, CPT1B, HADH, and PDK4). Consistently, protein abundance of OxPhos subunits encoded by both nuclear (SDHA and UQCRC1) and mitochondrial DNA (ND6) and protein abundance and phosphorylation of AMP-activated protein kinase and p38 MAPK were unaffected by testosterone therapy.ConclusionThe beneficial effect of testosterone treatment on lipid oxidation is not explained by increased abundance or phosphorylation-dependent activity of enzymes known to regulate mitochondrial biogenesis or markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels.</description><subject>Aging - physiology</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Body Composition - drug effects</subject><subject>Body Composition - physiology</subject><subject>Clinical Study</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Endocrinopathies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Lipid Metabolism - physiology</subject><subject>Medical sciences</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Oxidative Phosphorylation - drug effects</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Testosterone - pharmacology</subject><subject>Vertebrates: endocrinology</subject><issn>0804-4643</issn><issn>1479-683X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EotvCiTvyBQmpCtiJ4zhHVC1fqsQFJG7RxBl3DU682E6hP4d_yqx2-ThxsMbWPPN69L6MPZHihWwb8XL7fltJVQkh9D22karrK22az_fZRhihKqVVc8bOc_4ihKS7eMjOatVp0TZ6w35unUNbeHS8YC4xF0xxQR4XPkP6iikfWrMv0e7iMiUPgccffoLib5HvdzHTSXeB3jQCy8SD3_uJz1hgjMHnmXuSWrMNeFCCG7_cUHfh333Z8byOS0wziY4-wi34ACOB_67yiD1wEDI-PtUL9un19uPV2-r6w5t3V6-uq7HpTammpp1ai9jVRvbOtD22IERbgzHaigZHDUoZKaU1VjtUKAxarDvdOwQjuuaCPT_q7lP8ttICw-yzxRBgwbjmgbwma8lARejlEbUp5pzQDfvkya67QYoDJwbKZJBqOGRC9NOT8DrOOP1hf4dAwLMTANlCcAkW6_Nfzuhet3VPnDxy5FW2Hpfinbfw389_AcQhqLA</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Petersson, Stine J</creator><creator>Christensen, Louise L</creator><creator>Kristensen, Jonas M</creator><creator>Kruse, Rikke</creator><creator>Andersen, Marianne</creator><creator>Højlund, Kurt</creator><general>Bioscientifica Ltd</general><general>BioScientifica</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20140701</creationdate><title>Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone</title><author>Petersson, Stine J ; Christensen, Louise L ; Kristensen, Jonas M ; Kruse, Rikke ; Andersen, Marianne ; Højlund, Kurt</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b398t-d35d5cee72819f859e5a0052a886c03eb6a448111c8c6fe4e08ece2769fea8073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aging - physiology</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Body Composition - drug effects</topic><topic>Body Composition - physiology</topic><topic>Clinical Study</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Endocrinopathies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Lipid Metabolism - physiology</topic><topic>Medical sciences</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Oxidative Phosphorylation - drug effects</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Testosterone - pharmacology</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Petersson, Stine J</creatorcontrib><creatorcontrib>Christensen, Louise L</creatorcontrib><creatorcontrib>Kristensen, Jonas M</creatorcontrib><creatorcontrib>Kruse, Rikke</creatorcontrib><creatorcontrib>Andersen, Marianne</creatorcontrib><creatorcontrib>Højlund, Kurt</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Petersson, Stine J</au><au>Christensen, Louise L</au><au>Kristensen, Jonas M</au><au>Kruse, Rikke</au><au>Andersen, Marianne</au><au>Højlund, Kurt</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone</atitle><jtitle>European journal of endocrinology</jtitle><addtitle>Eur J Endocrinol</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>171</volume><issue>1</issue><spage>77</spage><epage>88</epage><pages>77-88</pages><issn>0804-4643</issn><eissn>1479-683X</eissn><abstract>ObjectiveRecent studies have indicated that serum testosterone in aging men is associated with insulin sensitivity and expression of genes involved in oxidative phosphorylation (OxPhos), and that testosterone treatment increases lipid oxidation. Herein, we investigated the effect of testosterone therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels.MethodsSkeletal muscle biopsies were obtained before and after treatment with either testosterone gel (n=12) or placebo (n=13) for 6 months. Insulin sensitivity and substrate oxidation were assessed by euglycemic–hyperinsulinemic clamp and indirect calorimetry. Muscle mRNA levels and protein abundance and phosphorylation of enzymes involved in mitochondrial biogenesis, OxPhos, and lipid metabolism were examined by quantitative real-time PCR and western blotting.ResultsDespite an increase in lipid oxidation (P<0.05), testosterone therapy had no effect on insulin sensitivity or mRNA levels of genes involved in mitochondrial biogenesis (PPARGC1A, PRKAA2, and PRKAG3), OxPhos (NDUFS1, ETFA, SDHA, UQCRC1, and COX5B), or lipid metabolism (ACADVL, CD36, CPT1B, HADH, and PDK4). Consistently, protein abundance of OxPhos subunits encoded by both nuclear (SDHA and UQCRC1) and mitochondrial DNA (ND6) and protein abundance and phosphorylation of AMP-activated protein kinase and p38 MAPK were unaffected by testosterone therapy.ConclusionThe beneficial effect of testosterone treatment on lipid oxidation is not explained by increased abundance or phosphorylation-dependent activity of enzymes known to regulate mitochondrial biogenesis or markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels.</abstract><cop>Bristol</cop><pub>Bioscientifica Ltd</pub><pmid>24760536</pmid><doi>10.1530/EJE-14-0006</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aging - physiology Biological and medical sciences Blotting, Western Body Composition - drug effects Body Composition - physiology Clinical Study Electrophoresis, Polyacrylamide Gel Endocrinopathies Fundamental and applied biological sciences. Psychology Lipid Metabolism - physiology Medical sciences Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Oxidative Phosphorylation - drug effects Real-Time Polymerase Chain Reaction Testosterone - pharmacology Vertebrates: endocrinology |
| title | Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone |
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