Oral 3‐hydroxybutyrate ingestion decreases endogenous glucose production, lipolysis, and hormone‐sensitive lipase phosphorylation in adipose tissue in men: a human randomized, controlled, crossover trial
Aims To test whether oral administration of D/L‐3‐hydroxybutyrate as a sodium salt inhibits lipolysis and intracellular lipid signalling, in particular, hormone‐sensitive lipase, and whether D/L‐3‐hydroxybutyrate alters endogenous glucose production. Methods We studied six young men in a randomized,...
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| Veröffentlicht in: | Diabetic medicine 2021-02, Vol.38 (2), p.e14385-n/a |
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| creator | Svart, M. Rittig, N. Pedersen, S.B. Jessen, N. Møller, N. |
| description | Aims
To test whether oral administration of D/L‐3‐hydroxybutyrate as a sodium salt inhibits lipolysis and intracellular lipid signalling, in particular, hormone‐sensitive lipase, and whether D/L‐3‐hydroxybutyrate alters endogenous glucose production.
Methods
We studied six young men in a randomized, controlled, crossover study after ingestion of Na‐D/L‐3‐hydroxybutyrate (hyperketotic condition) or saline (placebo control). We quantified lipolysis and endogenous glucose production using [9,10‐3H]‐palmitate and [3‐3H]glucose tracers, and adipose tissue biopsies were collected to investigate key lipolytic enzymes.
Results
After ingestion, D/L‐3‐hydroxybutyrate increased by more than 2.5 mmol/l, free fatty acid concentrations decreased by >70%, and palmitate rate of appearance was halved. Protein kinase A phosphorylation of perilipin was reduced and hormone‐sensitive lipase 660 phosphorylation in adipose tissue biopsies was 70–80% decreased in the hyperketotic condition and unchanged in the control. Compared to the control, endogenous glucose production was reduced by close to 20% (P |
| doi_str_mv | 10.1111/dme.14385 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2434481809</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2434481809</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3535-33fee64bbd6303abc7e4bda96ca783837191ea504b6930600e0ab93bd05761f53</originalsourceid><addsrcrecordid>eNp1kc9u1DAQxi0EokvhwAsgS1xA2rR27CROb6h_AKmoFzhHdjy768qxFztum554BN6Md-BJ6uwWDkhYGtnS_OYbz3wIvabkiOZzrAc4opyJ6glaUF7zouItfYoWpOFlwUhDD9CLGK8JoWXL2ufogJVNyytRLtCvqyAtZr9__NxMOvi7SaVxCnIEbNwa4mi8wxr6ADJCxOC0X4PzKeK1Tb2PgLfB69TP3BJbs_V2iiYusXQab3wYvIOsHcFFM5obmBE5V218zBEmK3ctjMNS5-qcGk2MaW6PB3AnWOJNGqTDISv6wdyDXuLeuzF4a3fv4GP0NxDwGIy0L9GzlbQRXj3eh-jbxfnX00_F5dXHz6cfLoueVawqGFsB1FwpXTPCpOob4ErLtu5lI5hgDW0pyIpwVbeM1IQAkaplSpOqqemqYofo3V43z_895UV1g4k9WCsd5PV0JWecCypIm9G3_6DXPgWXf5cpURJBSzFT7_fUbqAAq24bzCDD1FHSzS532eVu53Jm3zwqJjWA_kv-sTUDx3vg1liY_q_UnX0530s-AI3DuOg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2482081289</pqid></control><display><type>article</type><title>Oral 3‐hydroxybutyrate ingestion decreases endogenous glucose production, lipolysis, and hormone‐sensitive lipase phosphorylation in adipose tissue in men: a human randomized, controlled, crossover trial</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Svart, M. ; Rittig, N. ; Pedersen, S.B. ; Jessen, N. ; Møller, N.</creator><creatorcontrib>Svart, M. ; Rittig, N. ; Pedersen, S.B. ; Jessen, N. ; Møller, N.</creatorcontrib><description>Aims
To test whether oral administration of D/L‐3‐hydroxybutyrate as a sodium salt inhibits lipolysis and intracellular lipid signalling, in particular, hormone‐sensitive lipase, and whether D/L‐3‐hydroxybutyrate alters endogenous glucose production.
Methods
We studied six young men in a randomized, controlled, crossover study after ingestion of Na‐D/L‐3‐hydroxybutyrate (hyperketotic condition) or saline (placebo control). We quantified lipolysis and endogenous glucose production using [9,10‐3H]‐palmitate and [3‐3H]glucose tracers, and adipose tissue biopsies were collected to investigate key lipolytic enzymes.
Results
After ingestion, D/L‐3‐hydroxybutyrate increased by more than 2.5 mmol/l, free fatty acid concentrations decreased by >70%, and palmitate rate of appearance was halved. Protein kinase A phosphorylation of perilipin was reduced and hormone‐sensitive lipase 660 phosphorylation in adipose tissue biopsies was 70–80% decreased in the hyperketotic condition and unchanged in the control. Compared to the control, endogenous glucose production was reduced by close to 20% (P<0.05) after 3‐hydroxybutyrate ingestion.
Conclusion
We conclude that oral D/L‐Na‐3‐hydroxybutyrate increases D/L‐3‐hydroxybutyrate concentrations within half an hour, decreases free fatty acid concentrations, lowers lipolysis and endogenous glucose production, and dephosphorylates hormone‐sensitive lipase. Collectively these phenomena may be viewed as an orchestrated feedback loop, controlling endogenous glucose production, lipolysis and ketogenesis. Such effects would be beneficial in insulin‐resistant states.
(www.clinicaltrials.gov ID number: NCT02917252)</description><identifier>ISSN: 0742-3071</identifier><identifier>EISSN: 1464-5491</identifier><identifier>DOI: 10.1111/dme.14385</identifier><identifier>PMID: 32794582</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>3-Hydroxybutyric Acid - pharmacology ; Adipose tissue ; Adipose Tissue - drug effects ; Adipose Tissue - metabolism ; Adult ; Biopsy ; Cross-Over Studies ; Cyclic AMP-Dependent Protein Kinases - drug effects ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Diabetes ; Fatty acids ; Feedback, Physiological ; Gluconeogenesis - drug effects ; Glucose ; Humans ; Insulin ; Intracellular signalling ; Ketogenesis ; Kinases ; Lipase ; Lipolysis ; Lipolysis - drug effects ; Male ; Mens health ; Oral administration ; Palmitic acid ; Perilipin-1 - drug effects ; Perilipin-1 - metabolism ; Phosphorylation ; Phosphorylation - drug effects ; Placebos ; Protein kinase A ; Random Allocation ; Sterol Esterase - drug effects ; Sterol Esterase - metabolism ; Tracers ; Young Adult</subject><ispartof>Diabetic medicine, 2021-02, Vol.38 (2), p.e14385-n/a</ispartof><rights>2020 Diabetes UK</rights><rights>2020 Diabetes UK.</rights><rights>Diabetic Medicine © 2021 Diabetes UK</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3535-33fee64bbd6303abc7e4bda96ca783837191ea504b6930600e0ab93bd05761f53</citedby><cites>FETCH-LOGICAL-c3535-33fee64bbd6303abc7e4bda96ca783837191ea504b6930600e0ab93bd05761f53</cites><orcidid>0000-0001-9938-2181 ; 0000-0002-7838-8063 ; 0000-0002-9574-0612 ; 0000-0001-5627-7322 ; 0000-0001-5613-7274</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdme.14385$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdme.14385$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32794582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Svart, M.</creatorcontrib><creatorcontrib>Rittig, N.</creatorcontrib><creatorcontrib>Pedersen, S.B.</creatorcontrib><creatorcontrib>Jessen, N.</creatorcontrib><creatorcontrib>Møller, N.</creatorcontrib><title>Oral 3‐hydroxybutyrate ingestion decreases endogenous glucose production, lipolysis, and hormone‐sensitive lipase phosphorylation in adipose tissue in men: a human randomized, controlled, crossover trial</title><title>Diabetic medicine</title><addtitle>Diabet Med</addtitle><description>Aims
To test whether oral administration of D/L‐3‐hydroxybutyrate as a sodium salt inhibits lipolysis and intracellular lipid signalling, in particular, hormone‐sensitive lipase, and whether D/L‐3‐hydroxybutyrate alters endogenous glucose production.
Methods
We studied six young men in a randomized, controlled, crossover study after ingestion of Na‐D/L‐3‐hydroxybutyrate (hyperketotic condition) or saline (placebo control). We quantified lipolysis and endogenous glucose production using [9,10‐3H]‐palmitate and [3‐3H]glucose tracers, and adipose tissue biopsies were collected to investigate key lipolytic enzymes.
Results
After ingestion, D/L‐3‐hydroxybutyrate increased by more than 2.5 mmol/l, free fatty acid concentrations decreased by >70%, and palmitate rate of appearance was halved. Protein kinase A phosphorylation of perilipin was reduced and hormone‐sensitive lipase 660 phosphorylation in adipose tissue biopsies was 70–80% decreased in the hyperketotic condition and unchanged in the control. Compared to the control, endogenous glucose production was reduced by close to 20% (P<0.05) after 3‐hydroxybutyrate ingestion.
Conclusion
We conclude that oral D/L‐Na‐3‐hydroxybutyrate increases D/L‐3‐hydroxybutyrate concentrations within half an hour, decreases free fatty acid concentrations, lowers lipolysis and endogenous glucose production, and dephosphorylates hormone‐sensitive lipase. Collectively these phenomena may be viewed as an orchestrated feedback loop, controlling endogenous glucose production, lipolysis and ketogenesis. Such effects would be beneficial in insulin‐resistant states.
(www.clinicaltrials.gov ID number: NCT02917252)</description><subject>3-Hydroxybutyric Acid - pharmacology</subject><subject>Adipose tissue</subject><subject>Adipose Tissue - drug effects</subject><subject>Adipose Tissue - metabolism</subject><subject>Adult</subject><subject>Biopsy</subject><subject>Cross-Over Studies</subject><subject>Cyclic AMP-Dependent Protein Kinases - drug effects</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Diabetes</subject><subject>Fatty acids</subject><subject>Feedback, Physiological</subject><subject>Gluconeogenesis - drug effects</subject><subject>Glucose</subject><subject>Humans</subject><subject>Insulin</subject><subject>Intracellular signalling</subject><subject>Ketogenesis</subject><subject>Kinases</subject><subject>Lipase</subject><subject>Lipolysis</subject><subject>Lipolysis - drug effects</subject><subject>Male</subject><subject>Mens health</subject><subject>Oral administration</subject><subject>Palmitic acid</subject><subject>Perilipin-1 - drug effects</subject><subject>Perilipin-1 - metabolism</subject><subject>Phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Placebos</subject><subject>Protein kinase A</subject><subject>Random Allocation</subject><subject>Sterol Esterase - drug effects</subject><subject>Sterol Esterase - metabolism</subject><subject>Tracers</subject><subject>Young Adult</subject><issn>0742-3071</issn><issn>1464-5491</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9u1DAQxi0EokvhwAsgS1xA2rR27CROb6h_AKmoFzhHdjy768qxFztum554BN6Md-BJ6uwWDkhYGtnS_OYbz3wIvabkiOZzrAc4opyJ6glaUF7zouItfYoWpOFlwUhDD9CLGK8JoWXL2ufogJVNyytRLtCvqyAtZr9__NxMOvi7SaVxCnIEbNwa4mi8wxr6ADJCxOC0X4PzKeK1Tb2PgLfB69TP3BJbs_V2iiYusXQab3wYvIOsHcFFM5obmBE5V218zBEmK3ctjMNS5-qcGk2MaW6PB3AnWOJNGqTDISv6wdyDXuLeuzF4a3fv4GP0NxDwGIy0L9GzlbQRXj3eh-jbxfnX00_F5dXHz6cfLoueVawqGFsB1FwpXTPCpOob4ErLtu5lI5hgDW0pyIpwVbeM1IQAkaplSpOqqemqYofo3V43z_895UV1g4k9WCsd5PV0JWecCypIm9G3_6DXPgWXf5cpURJBSzFT7_fUbqAAq24bzCDD1FHSzS532eVu53Jm3zwqJjWA_kv-sTUDx3vg1liY_q_UnX0530s-AI3DuOg</recordid><startdate>202102</startdate><enddate>202102</enddate><creator>Svart, M.</creator><creator>Rittig, N.</creator><creator>Pedersen, S.B.</creator><creator>Jessen, N.</creator><creator>Møller, N.</creator><general>Wiley Subscription Services, Inc</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>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9938-2181</orcidid><orcidid>https://orcid.org/0000-0002-7838-8063</orcidid><orcidid>https://orcid.org/0000-0002-9574-0612</orcidid><orcidid>https://orcid.org/0000-0001-5627-7322</orcidid><orcidid>https://orcid.org/0000-0001-5613-7274</orcidid></search><sort><creationdate>202102</creationdate><title>Oral 3‐hydroxybutyrate ingestion decreases endogenous glucose production, lipolysis, and hormone‐sensitive lipase phosphorylation in adipose tissue in men: a human randomized, controlled, crossover trial</title><author>Svart, M. ; Rittig, N. ; Pedersen, S.B. ; Jessen, N. ; Møller, N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3535-33fee64bbd6303abc7e4bda96ca783837191ea504b6930600e0ab93bd05761f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>3-Hydroxybutyric Acid - pharmacology</topic><topic>Adipose tissue</topic><topic>Adipose Tissue - drug effects</topic><topic>Adipose Tissue - metabolism</topic><topic>Adult</topic><topic>Biopsy</topic><topic>Cross-Over Studies</topic><topic>Cyclic AMP-Dependent Protein Kinases - drug effects</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Diabetes</topic><topic>Fatty acids</topic><topic>Feedback, Physiological</topic><topic>Gluconeogenesis - drug effects</topic><topic>Glucose</topic><topic>Humans</topic><topic>Insulin</topic><topic>Intracellular signalling</topic><topic>Ketogenesis</topic><topic>Kinases</topic><topic>Lipase</topic><topic>Lipolysis</topic><topic>Lipolysis - drug effects</topic><topic>Male</topic><topic>Mens health</topic><topic>Oral administration</topic><topic>Palmitic acid</topic><topic>Perilipin-1 - drug effects</topic><topic>Perilipin-1 - metabolism</topic><topic>Phosphorylation</topic><topic>Phosphorylation - drug effects</topic><topic>Placebos</topic><topic>Protein kinase A</topic><topic>Random Allocation</topic><topic>Sterol Esterase - drug effects</topic><topic>Sterol Esterase - metabolism</topic><topic>Tracers</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Svart, M.</creatorcontrib><creatorcontrib>Rittig, N.</creatorcontrib><creatorcontrib>Pedersen, S.B.</creatorcontrib><creatorcontrib>Jessen, N.</creatorcontrib><creatorcontrib>Møller, N.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetic medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Svart, M.</au><au>Rittig, N.</au><au>Pedersen, S.B.</au><au>Jessen, N.</au><au>Møller, N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oral 3‐hydroxybutyrate ingestion decreases endogenous glucose production, lipolysis, and hormone‐sensitive lipase phosphorylation in adipose tissue in men: a human randomized, controlled, crossover trial</atitle><jtitle>Diabetic medicine</jtitle><addtitle>Diabet Med</addtitle><date>2021-02</date><risdate>2021</risdate><volume>38</volume><issue>2</issue><spage>e14385</spage><epage>n/a</epage><pages>e14385-n/a</pages><issn>0742-3071</issn><eissn>1464-5491</eissn><abstract>Aims
To test whether oral administration of D/L‐3‐hydroxybutyrate as a sodium salt inhibits lipolysis and intracellular lipid signalling, in particular, hormone‐sensitive lipase, and whether D/L‐3‐hydroxybutyrate alters endogenous glucose production.
Methods
We studied six young men in a randomized, controlled, crossover study after ingestion of Na‐D/L‐3‐hydroxybutyrate (hyperketotic condition) or saline (placebo control). We quantified lipolysis and endogenous glucose production using [9,10‐3H]‐palmitate and [3‐3H]glucose tracers, and adipose tissue biopsies were collected to investigate key lipolytic enzymes.
Results
After ingestion, D/L‐3‐hydroxybutyrate increased by more than 2.5 mmol/l, free fatty acid concentrations decreased by >70%, and palmitate rate of appearance was halved. Protein kinase A phosphorylation of perilipin was reduced and hormone‐sensitive lipase 660 phosphorylation in adipose tissue biopsies was 70–80% decreased in the hyperketotic condition and unchanged in the control. Compared to the control, endogenous glucose production was reduced by close to 20% (P<0.05) after 3‐hydroxybutyrate ingestion.
Conclusion
We conclude that oral D/L‐Na‐3‐hydroxybutyrate increases D/L‐3‐hydroxybutyrate concentrations within half an hour, decreases free fatty acid concentrations, lowers lipolysis and endogenous glucose production, and dephosphorylates hormone‐sensitive lipase. Collectively these phenomena may be viewed as an orchestrated feedback loop, controlling endogenous glucose production, lipolysis and ketogenesis. Such effects would be beneficial in insulin‐resistant states.
(www.clinicaltrials.gov ID number: NCT02917252)</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32794582</pmid><doi>10.1111/dme.14385</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-9938-2181</orcidid><orcidid>https://orcid.org/0000-0002-7838-8063</orcidid><orcidid>https://orcid.org/0000-0002-9574-0612</orcidid><orcidid>https://orcid.org/0000-0001-5627-7322</orcidid><orcidid>https://orcid.org/0000-0001-5613-7274</orcidid></addata></record> |
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| ispartof | Diabetic medicine, 2021-02, Vol.38 (2), p.e14385-n/a |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | 3-Hydroxybutyric Acid - pharmacology Adipose tissue Adipose Tissue - drug effects Adipose Tissue - metabolism Adult Biopsy Cross-Over Studies Cyclic AMP-Dependent Protein Kinases - drug effects Cyclic AMP-Dependent Protein Kinases - metabolism Diabetes Fatty acids Feedback, Physiological Gluconeogenesis - drug effects Glucose Humans Insulin Intracellular signalling Ketogenesis Kinases Lipase Lipolysis Lipolysis - drug effects Male Mens health Oral administration Palmitic acid Perilipin-1 - drug effects Perilipin-1 - metabolism Phosphorylation Phosphorylation - drug effects Placebos Protein kinase A Random Allocation Sterol Esterase - drug effects Sterol Esterase - metabolism Tracers Young Adult |
| title | Oral 3‐hydroxybutyrate ingestion decreases endogenous glucose production, lipolysis, and hormone‐sensitive lipase phosphorylation in adipose tissue in men: a human randomized, controlled, crossover trial |
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