Involvement of the Neutral Amino Acid Transporter SLC6A15 and Leucine in Obesity-Related Phenotypes

Jana Drgonova, Josefin A. Jacobsson, Joan Han, Jack A. Yanovski, Robert Fredriksson, Claude Marcus, Helgi B. Schiöth, George R. Uhl

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere68245
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 4 2013

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Neutral Amino Acid Transport Systems
amino acid transporters
Leucine
leucine
Branched Chain Amino Acids
Solitary Nucleus
obesity
branched chain amino acids
Obesity
hypothalamus
Nutrition
Phenotype
phenotype
Metabolism
Hypothalamus
food intake
Brain
Eating
brain
Aptitude

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Drgonova, J., Jacobsson, J. A., Han, J., Yanovski, J. A., Fredriksson, R., Marcus, C., ... Uhl, G. R. (2013). Involvement of the Neutral Amino Acid Transporter SLC6A15 and Leucine in Obesity-Related Phenotypes. PloS one, 8(9), [e68245]. https://doi.org/10.1371/journal.pone.0068245

Involvement of the Neutral Amino Acid Transporter SLC6A15 and Leucine in Obesity-Related Phenotypes. / Drgonova, Jana; Jacobsson, Josefin A.; Han, Joan; Yanovski, Jack A.; Fredriksson, Robert; Marcus, Claude; Schiöth, Helgi B.; Uhl, George R.

In: PloS one, Vol. 8, No. 9, e68245, 04.09.2013.

Research output: Contribution to journalArticle

Drgonova, J, Jacobsson, JA, Han, J, Yanovski, JA, Fredriksson, R, Marcus, C, Schiöth, HB & Uhl, GR 2013, 'Involvement of the Neutral Amino Acid Transporter SLC6A15 and Leucine in Obesity-Related Phenotypes', PloS one, vol. 8, no. 9, e68245. https://doi.org/10.1371/journal.pone.0068245
Drgonova, Jana ; Jacobsson, Josefin A. ; Han, Joan ; Yanovski, Jack A. ; Fredriksson, Robert ; Marcus, Claude ; Schiöth, Helgi B. ; Uhl, George R. / Involvement of the Neutral Amino Acid Transporter SLC6A15 and Leucine in Obesity-Related Phenotypes. In: PloS one. 2013 ; Vol. 8, No. 9.
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