Involvement of the neutral amino acid transporter SLC6A15 and leucine in obesity-related phenotypes
Brain pathways, including those in hypothalamus and nucleus of the solitary tract, influence food intake, nutrient preferences, metabolism and development of obesity in ways that often differ between males and females. Branched chain amino acids, including leucine, can suppress food intake, alter me...
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| creator | Drgonova, Jana Jacobsson, Josefin A Han, Joan C Yanovski, Jack A Fredriksson, Robert Marcus, Claude Schiöth, Helgi B Uhl, George R |
| description | Brain pathways, including those in hypothalamus and nucleus of the solitary tract, influence food intake, nutrient preferences, metabolism and development of obesity in ways that often differ between males and females. Branched chain amino acids, including leucine, can suppress food intake, alter metabolism and change vulnerability to obesity. The SLC6A15 (v7-3) gene encodes a sodium-dependent transporter of leucine and other branched chain amino acids that is expressed by neurons in hypothalamus and nucleus of the solitary tract. We now report that SLC6A15 knockout attenuates leucine's abilities to reduce both: a) intake of normal chow and b) weight gain produced by access to a high fat diet in gender-selective fashions. We identify SNPs in the human SLC6A15 that are associated with body mass index and insulin resistance in males. These observations in mice and humans support a novel, gender-selective role for brain amino acid compartmentalization mediated by SLC6A15 in diet and obesity-associated phenotypes. |
| doi_str_mv | 10.1371/journal.pone.0068245 |
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Branched chain amino acids, including leucine, can suppress food intake, alter metabolism and change vulnerability to obesity. The SLC6A15 (v7-3) gene encodes a sodium-dependent transporter of leucine and other branched chain amino acids that is expressed by neurons in hypothalamus and nucleus of the solitary tract. We now report that SLC6A15 knockout attenuates leucine's abilities to reduce both: a) intake of normal chow and b) weight gain produced by access to a high fat diet in gender-selective fashions. We identify SNPs in the human SLC6A15 that are associated with body mass index and insulin resistance in males. These observations in mice and humans support a novel, gender-selective role for brain amino acid compartmentalization mediated by SLC6A15 in diet and obesity-associated phenotypes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0068245</identifier><identifier>PMID: 24023709</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Amino Acid Transport Systems, Neutral - genetics ; Amino Acid Transport Systems, Neutral - metabolism ; Amino acids ; Animals ; Body mass ; Body mass index ; Body size ; Body weight gain ; Brain ; Branched chain amino acids ; Chain branching ; Chains ; Child ; Child, Preschool ; Eating - drug effects ; Female ; Females ; Food intake ; Food preferences ; Genetic aspects ; Genotype ; High fat diet ; Humans ; Hypothalamus ; Insulin ; Insulin resistance ; Leucine ; Leucine - metabolism ; Leucine - pharmacology ; Male ; Males ; Medicin och hälsovetenskap ; Metabolism ; Mice ; Mice, Knockout ; Neurosciences ; Nuclei ; Obesity ; Obesity - chemically induced ; Obesity - genetics ; Obesity - metabolism ; Phenotypes ; Physiological aspects ; Polymorphism, Single Nucleotide - genetics ; Rodents ; Single-nucleotide polymorphism ; Sodium ; Solitary tract nucleus ; Weight reduction ; Young Adult</subject><ispartof>PloS one, 2013-09, Vol.8 (9), p.e68245</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. 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Branched chain amino acids, including leucine, can suppress food intake, alter metabolism and change vulnerability to obesity. The SLC6A15 (v7-3) gene encodes a sodium-dependent transporter of leucine and other branched chain amino acids that is expressed by neurons in hypothalamus and nucleus of the solitary tract. We now report that SLC6A15 knockout attenuates leucine's abilities to reduce both: a) intake of normal chow and b) weight gain produced by access to a high fat diet in gender-selective fashions. We identify SNPs in the human SLC6A15 that are associated with body mass index and insulin resistance in males. These observations in mice and humans support a novel, gender-selective role for brain amino acid compartmentalization mediated by SLC6A15 in diet and obesity-associated phenotypes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24023709</pmid><doi>10.1371/journal.pone.0068245</doi><tpages>e68245</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2013-09, Vol.8 (9), p.e68245 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adolescent Amino Acid Transport Systems, Neutral - genetics Amino Acid Transport Systems, Neutral - metabolism Amino acids Animals Body mass Body mass index Body size Body weight gain Brain Branched chain amino acids Chain branching Chains Child Child, Preschool Eating - drug effects Female Females Food intake Food preferences Genetic aspects Genotype High fat diet Humans Hypothalamus Insulin Insulin resistance Leucine Leucine - metabolism Leucine - pharmacology Male Males Medicin och hälsovetenskap Metabolism Mice Mice, Knockout Neurosciences Nuclei Obesity Obesity - chemically induced Obesity - genetics Obesity - metabolism Phenotypes Physiological aspects Polymorphism, Single Nucleotide - genetics Rodents Single-nucleotide polymorphism Sodium Solitary tract nucleus Weight reduction Young Adult |
| title | Involvement of the neutral amino acid transporter SLC6A15 and leucine in obesity-related phenotypes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-04T04%3A39%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Involvement%20of%20the%20neutral%20amino%20acid%20transporter%20SLC6A15%20and%20leucine%20in%20obesity-related%20phenotypes&rft.jtitle=PloS%20one&rft.au=Drgonova,%20Jana&rft.date=2013-09-04&rft.volume=8&rft.issue=9&rft.spage=e68245&rft.pages=e68245-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0068245&rft_dat=%3Cgale_plos_%3EA478425600%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1430192812&rft_id=info:pmid/24023709&rft_galeid=A478425600&rft_doaj_id=oai_doaj_org_article_d3ca691d021a4d298989253ee80b807f&rfr_iscdi=true |