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Fructose ingestion acutely stimulates circulating FGF21 levels in humans

Abstract Objective Fibroblast growth factor 21 (FGF21) is a hormone with pleiotropic metabolic activities which, in rodents, is robustly regulated by fasting and ketogenic diets. In contrast, similar dietary interventions have either no or minimal effects on circulating FGF21 in humans. Moreover, no...

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Published in:Molecular metabolism (Germany) 2015-01, Vol.4 (1), p.51-57
Main Authors: Dushay, Jody R, Toschi, Elena, Mitten, Emilie K, Fisher, Ffolliott M, Herman, Mark A, Maratos-Flier, Eleftheria
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container_title Molecular metabolism (Germany)
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creator Dushay, Jody R
Toschi, Elena
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description Abstract Objective Fibroblast growth factor 21 (FGF21) is a hormone with pleiotropic metabolic activities which, in rodents, is robustly regulated by fasting and ketogenic diets. In contrast, similar dietary interventions have either no or minimal effects on circulating FGF21 in humans. Moreover, no intervention or dietary challenge has been shown to acutely stimulate circulating FGF21 in either humans or animals. Recent animal data suggest that the transcription factor Carbohydrate Responsive-Element Binding Protein (ChREBP) stimulates hepatic FGF21 expression and that fructose may activate hepatic ChREBP more robustly than glucose. Here, we examined whether fructose ingestion can acutely stimulate FGF21 in humans. Methods We measured serum FGF21, glucose, insulin, and triglyceride levels in ten lean, healthy adults and eleven adults with the metabolic syndrome following oral ingestion of 75 g of glucose, fructose, or a combination of the two sugars. Results FGF21 levels rose rapidly following fructose ingestion, achieved a mean 3.4-fold increase at two hours ( P  
doi_str_mv 10.1016/j.molmet.2014.09.008
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In contrast, similar dietary interventions have either no or minimal effects on circulating FGF21 in humans. Moreover, no intervention or dietary challenge has been shown to acutely stimulate circulating FGF21 in either humans or animals. Recent animal data suggest that the transcription factor Carbohydrate Responsive-Element Binding Protein (ChREBP) stimulates hepatic FGF21 expression and that fructose may activate hepatic ChREBP more robustly than glucose. Here, we examined whether fructose ingestion can acutely stimulate FGF21 in humans. Methods We measured serum FGF21, glucose, insulin, and triglyceride levels in ten lean, healthy adults and eleven adults with the metabolic syndrome following oral ingestion of 75 g of glucose, fructose, or a combination of the two sugars. Results FGF21 levels rose rapidly following fructose ingestion, achieved a mean 3.4-fold increase at two hours ( P  &lt; 0.01), and returned to baseline levels within five hours. In contrast, FGF21 did not increase in the first two hours following ingestion of a glucose load, although more modest increases were observed after three to four hours. Both baseline and fructose-stimulated FGF21 levels were 2–3 fold elevated in subjects with metabolic syndrome. Conclusions Fructose ingestion acutely and robustly increases serum FGF21 levels in humans in a pattern consistent with a hormonal response. While FGF21 appears to be critical for the adaptive response to fasting or starvation in rodents, these findings suggest that in humans, FGF21 may play an important role in fructose metabolism.</description><identifier>ISSN: 2212-8778</identifier><identifier>EISSN: 2212-8778</identifier><identifier>DOI: 10.1016/j.molmet.2014.09.008</identifier><identifier>PMID: 25685689</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Brief Communication ; ChREBP ; Endocrinology &amp; Metabolism ; FGF21 ; Fructose ; Metabolic syndrome</subject><ispartof>Molecular metabolism (Germany), 2015-01, Vol.4 (1), p.51-57</ispartof><rights>The Authors</rights><rights>2014 The Authors</rights><rights>2014 The Authors 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c584t-7eb4d93486efb7187974a694f40b9a73d5f55a64c3c6f09253abf49ad93156b13</citedby><cites>FETCH-LOGICAL-c584t-7eb4d93486efb7187974a694f40b9a73d5f55a64c3c6f09253abf49ad93156b13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314524/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S2212877814001653$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,3536,27901,27902,45756,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25685689$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dushay, Jody R</creatorcontrib><creatorcontrib>Toschi, Elena</creatorcontrib><creatorcontrib>Mitten, Emilie K</creatorcontrib><creatorcontrib>Fisher, Ffolliott M</creatorcontrib><creatorcontrib>Herman, Mark A</creatorcontrib><creatorcontrib>Maratos-Flier, Eleftheria</creatorcontrib><title>Fructose ingestion acutely stimulates circulating FGF21 levels in humans</title><title>Molecular metabolism (Germany)</title><addtitle>Mol Metab</addtitle><description>Abstract Objective Fibroblast growth factor 21 (FGF21) is a hormone with pleiotropic metabolic activities which, in rodents, is robustly regulated by fasting and ketogenic diets. In contrast, similar dietary interventions have either no or minimal effects on circulating FGF21 in humans. Moreover, no intervention or dietary challenge has been shown to acutely stimulate circulating FGF21 in either humans or animals. Recent animal data suggest that the transcription factor Carbohydrate Responsive-Element Binding Protein (ChREBP) stimulates hepatic FGF21 expression and that fructose may activate hepatic ChREBP more robustly than glucose. Here, we examined whether fructose ingestion can acutely stimulate FGF21 in humans. Methods We measured serum FGF21, glucose, insulin, and triglyceride levels in ten lean, healthy adults and eleven adults with the metabolic syndrome following oral ingestion of 75 g of glucose, fructose, or a combination of the two sugars. Results FGF21 levels rose rapidly following fructose ingestion, achieved a mean 3.4-fold increase at two hours ( P  &lt; 0.01), and returned to baseline levels within five hours. In contrast, FGF21 did not increase in the first two hours following ingestion of a glucose load, although more modest increases were observed after three to four hours. Both baseline and fructose-stimulated FGF21 levels were 2–3 fold elevated in subjects with metabolic syndrome. Conclusions Fructose ingestion acutely and robustly increases serum FGF21 levels in humans in a pattern consistent with a hormonal response. While FGF21 appears to be critical for the adaptive response to fasting or starvation in rodents, these findings suggest that in humans, FGF21 may play an important role in fructose metabolism.</description><subject>Brief Communication</subject><subject>ChREBP</subject><subject>Endocrinology &amp; Metabolism</subject><subject>FGF21</subject><subject>Fructose</subject><subject>Metabolic syndrome</subject><issn>2212-8778</issn><issn>2212-8778</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqFUk1r3DAQFaWlCWn-QSk-9rKuJOvDuhRK6CaFQA5tz4MsjxNtZSuV7IX995HZNE1zqRBohOa90bw3hLxntGaUqU-7eoxhxLnmlImamprS9hU55ZzxTat1-_pZfELOc97RslqllGRvyQmXqi3bnJKrbVrcHDNWfrrFPPs4VdYtM4ZDVW7jEuyMuXI-uTUsSdX2cstZFXCPIRdUdbeMdsrvyJvBhoznj-cZ-bn9-uPianN9c_nt4sv1xslWzBuNnehNI1qFQ6dZq40WVhkxCNoZq5teDlJaJVzj1EANl43tBmFswTCpOtackc9H3vulG7F3OM3JBrhPfrTpANF6-Pdl8ndwG_cgGiYkF4Xg4yNBir-X0jKMPjsMwU4YlwxMSam51EKXVHFMdSnmnHB4KsMorD7ADo4-wOoDUANF5AL78PyLT6A_qv_toSiIe48JsvM4Oex9QjdDH_3_KrwkcMFP3tnwCw-Yd3FJUzEBGGQOFL6vs7COAhO0cMqmeQAgVrEI</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Dushay, Jody R</creator><creator>Toschi, Elena</creator><creator>Mitten, Emilie K</creator><creator>Fisher, Ffolliott M</creator><creator>Herman, Mark A</creator><creator>Maratos-Flier, Eleftheria</creator><general>Elsevier GmbH</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150101</creationdate><title>Fructose ingestion acutely stimulates circulating FGF21 levels in humans</title><author>Dushay, Jody R ; Toschi, Elena ; Mitten, Emilie K ; Fisher, Ffolliott M ; Herman, Mark A ; Maratos-Flier, Eleftheria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c584t-7eb4d93486efb7187974a694f40b9a73d5f55a64c3c6f09253abf49ad93156b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Brief Communication</topic><topic>ChREBP</topic><topic>Endocrinology &amp; Metabolism</topic><topic>FGF21</topic><topic>Fructose</topic><topic>Metabolic syndrome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dushay, Jody R</creatorcontrib><creatorcontrib>Toschi, Elena</creatorcontrib><creatorcontrib>Mitten, Emilie K</creatorcontrib><creatorcontrib>Fisher, Ffolliott M</creatorcontrib><creatorcontrib>Herman, Mark A</creatorcontrib><creatorcontrib>Maratos-Flier, Eleftheria</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular metabolism (Germany)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dushay, Jody R</au><au>Toschi, Elena</au><au>Mitten, Emilie K</au><au>Fisher, Ffolliott M</au><au>Herman, Mark A</au><au>Maratos-Flier, Eleftheria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fructose ingestion acutely stimulates circulating FGF21 levels in humans</atitle><jtitle>Molecular metabolism (Germany)</jtitle><addtitle>Mol Metab</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>4</volume><issue>1</issue><spage>51</spage><epage>57</epage><pages>51-57</pages><issn>2212-8778</issn><eissn>2212-8778</eissn><abstract>Abstract Objective Fibroblast growth factor 21 (FGF21) is a hormone with pleiotropic metabolic activities which, in rodents, is robustly regulated by fasting and ketogenic diets. In contrast, similar dietary interventions have either no or minimal effects on circulating FGF21 in humans. Moreover, no intervention or dietary challenge has been shown to acutely stimulate circulating FGF21 in either humans or animals. Recent animal data suggest that the transcription factor Carbohydrate Responsive-Element Binding Protein (ChREBP) stimulates hepatic FGF21 expression and that fructose may activate hepatic ChREBP more robustly than glucose. Here, we examined whether fructose ingestion can acutely stimulate FGF21 in humans. Methods We measured serum FGF21, glucose, insulin, and triglyceride levels in ten lean, healthy adults and eleven adults with the metabolic syndrome following oral ingestion of 75 g of glucose, fructose, or a combination of the two sugars. Results FGF21 levels rose rapidly following fructose ingestion, achieved a mean 3.4-fold increase at two hours ( P  &lt; 0.01), and returned to baseline levels within five hours. In contrast, FGF21 did not increase in the first two hours following ingestion of a glucose load, although more modest increases were observed after three to four hours. Both baseline and fructose-stimulated FGF21 levels were 2–3 fold elevated in subjects with metabolic syndrome. Conclusions Fructose ingestion acutely and robustly increases serum FGF21 levels in humans in a pattern consistent with a hormonal response. While FGF21 appears to be critical for the adaptive response to fasting or starvation in rodents, these findings suggest that in humans, FGF21 may play an important role in fructose metabolism.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>25685689</pmid><doi>10.1016/j.molmet.2014.09.008</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Brief Communication
ChREBP
Endocrinology & Metabolism
FGF21
Fructose
Metabolic syndrome
title Fructose ingestion acutely stimulates circulating FGF21 levels in humans
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