title: The role of decreased levels of Niemann-Pick C1 intracellular cholesterol transport on obesity is reversed in the C57BL/6J, metabolic syndrome mouse strain: a metabolic or an inflammatory effect?
abstract: We have previously shown that decreased dosage of Niemann-Pick C1 (Npc1) protein, caused by heterozygosity at the null mutation, Npc1 (nih), locus, causes altered lipid metabolism in mice. When studied on the "lean" BALB/cJ genetic background, the decreased protein was associated with no weight changes in either males or females when on a regular diet but increased weights and adiposity when on a high fat diet Jelinek et al. (Obesity 18: 1457-1459, 2010, Gene 491:128-134, 2012). When the heterozygotes were studied on a mixed C57BL/6J, BALB/cJ background, increased weight and adiposity were also found on a regular diet (sexes pooled Jelinek et al. [Hum Molec Genet 20:312-321, 2011]). We find somewhat different results when the hypomorphic Npc1 mutation, Npc1 (nmf164), is studied on a pure C57BL/6J, "metabolic syndrome" genetic background with male, but not female, heterozygotes having lower weights on the regular diet. The result does not seem to be due to the difference in the two mutations as heterozygous Npc1 (nmf164) mice on the BALB/cJ background acted like the null mutant heterozygotes. Studies of glucose tolerance, liver enzymes, liver triglycerides and fat deposition, and adipose tissue caveolin 1 levels did not disclose reasons for these differing results.
authors.affiliation: Angel Charity for Children Wings For Genetic Research, Steele Childrens Research Center, Department of Pediatrics, University of Arizona, Tucson, AZ 85724-5073, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Borbon
authors.forename: Erin
authors.initials: E
authors.lastname: Campbell
authors.forename: Wangjing
authors.initials: W
authors.lastname: Ke
authors.forename: Robert P
authors.initials: RP
authors.lastname: Erickson
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001391:Azo Compounds; D001692:Biological Transport; D015153:Blotting, Western; D001835:Body Weight; D051242:Caveolin 1 / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D059305:Diet, High-Fat; D005260:Female; D006579:Heterozygote; D007249:Inflammation / Q000473:pathology*; D042541:Intracellular Space / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D052556:Niemann-Pick Disease, Type C / Q000097:blood / Q000150:complications / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D009929:Organ Size; D013194:Staining and Labeling; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001391:Azo Compounds; D051242:Caveolin 1; D014280:Triglycerides; D002784:Cholesterol; C011049:oil red O