title: Identification of genetic loci associated with different responses to high-fat diet-induced obesity in C57BL/6N and C57BL/6J substrains.
abstract: We have recently demonstrated that C57BL/6NTac and C57BL/6JRj substrains are significantly different in their response to high-fat diet-induced obesity (DIO). The C57BL/6JRj substrain seems to be protected from DIO and genetic differences between C57BL/6J and C57BL/6N substrains at 11 single nucleotide polymorphism (SNP) loci have been identified. To define genetic variants as well as differences in parameters of glucose homeostasis and insulin sensitivity between C57BL/6NTac and C57BL/6JRj substrains that may explain the different response to DIO, we analyzed 208 first backcross (BC1) hybrids of C57BL/6NTac and C57BL/6JRj [(C57BL/6NTac × C57BL/6JRj)F1 × C57BL/6NTac] mice. Body weight, epigonadal and subcutaneous fat mass, circulating leptin, as well as parameters of glucose metabolism were measured after 10 wk of high-fat diet (HFD). Genetic profiling of BC1 hybrids were performed using TaqMan SNP genotyping assays. Furthermore, to assess whether SNP polymorphisms could affect mRNA level, we carried out gene expression analysis in murine liver samples. Human subcutaneous adipose tissue was used to verify murine data of SNAP29. We identified four sex-specific variants that are associated with the extent of HFD-induced weight gain and fat depot mass. BC1 hybrids carrying the combination of risk or beneficial alleles exhibit the phenotypical extremes of the parental strains. Murine and human SC expression analysis revealed Snap29 as strongest candidate. Our data indicate an important role of these loci in responsiveness to HFD-induced obesity and suggest genes of the synaptic vesicle release system such as Snap29 being involved in the regulation of high-fat DIO.
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, Leipzig University, Leipzig, Germany; Institute of Biochemistry, Leipzig University, Leipzig, Germany;
authors.forename: John T
authors.initials: JT
authors.lastname: Heiker
authors.affiliation: IFB AdiposityDiseases, Junior Research Group 2 "Animal models of obesity", Leipzig University, Leipzig, Germany; and.
authors.forename: Anne
authors.initials: A
authors.lastname: Kunath
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, Leipzig University, Leipzig, Germany;
authors.forename: Joanna
authors.initials: J
authors.lastname: Kosacka
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, Leipzig University, Leipzig, Germany; IFB AdiposityDiseases, Leipzig University, Leipzig, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Flehmig
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, Leipzig University, Leipzig, Germany;
authors.forename: Anja
authors.initials: A
authors.lastname: Knigge
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, Leipzig University, Leipzig, Germany;
authors.forename: Matthias
authors.initials: M
authors.lastname: Kern
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, Leipzig University, Leipzig, Germany; IFB AdiposityDiseases, Leipzig University, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.affiliation: IFB AdiposityDiseases, Leipzig University, Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, Leipzig University, Leipzig, Germany; IFB AdiposityDiseases, Leipzig University, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: Department of Medicine, Endocrinology and Diabetes, Leipzig University, Leipzig, Germany; IFB AdiposityDiseases, Junior Research Group 2 "Animal models of obesity", Leipzig University, Leipzig, Germany; and nora.kloeting@medizin.uni-leipzig.de.
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000483:Alleles; D000818:Animals; D001835:Body Weight / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D015430:Weight Gain / Q000235:genetics
chemical_list: D020738:Leptin; D033921:Vesicular Transport Proteins; D005947:Glucose
keywords: C57BL/6; DIO; SNAP29; genetic background; high-fat diet; obesity; visceral fat mass