title: Involvement of the neutral amino acid transporter SLC6A15 and leucine in obesity-related phenotypes.
abstract: 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.
authors.affiliation: Molecular Neurobiology Branch, NIH-IRP, NIDA, Baltimore, Maryland, United States of America.
authors.forename: Jana
authors.initials: J
authors.lastname: Drgonova
authors.forename: Josefin A
authors.initials: JA
authors.lastname: Jacobsson
authors.forename: Joan C
authors.initials: JC
authors.lastname: Han
authors.forename: Jack A
authors.initials: JA
authors.lastname: Yanovski
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.forename: Claude
authors.initials: C
authors.lastname: Marcus
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
mesh_terms: D000293:Adolescent; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004435:Eating / Q000187:drug effects; D005260:Female; D005838:Genotype; D006801:Humans; D007930:Leucine / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C508691:Slc6a15 protein, mouse; D007930:Leucine
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