title: Overweight in mice and enhanced adipogenesis in vitro are associated with lack of the hedgehog coreceptor boc.
abstract: Obesity arises from a combination of genetic, environmental, and behavioral factors. However, the processes that regulate white adipose tissue (WAT) expansion at the level of the adipocyte are not well understood. The Hedgehog (HH) pathway plays a conserved role in adipogenesis, inhibiting fat formation in vivo and in vitro, but it has not been shown that mice with reduced HH pathway activity have enhanced adiposity. We report that mice lacking the HH coreceptor BOC displayed age-related overweight and excess WAT. They also displayed alterations in some metabolic parameters but normal food intake. Furthermore, they had an exacerbated response to a high-fat diet, including enhanced weight gain and adipocyte hypertrophy, livers with greater fat accumulation, and elevated expression of genes related to adipogenesis, lipid metabolism, and adipokine production. Cultured Boc(-/-) mouse embryo fibroblasts showed enhanced adipogenesis relative to Boc(+/+) cells, and they expressed reduced levels of HH pathway target genes. Therefore, a loss-of-function mutation in an HH pathway component is associated with WAT accumulation and overweight in mice. Variant alleles of such HH regulators may contribute to WAT accumulation in human individuals with additional genetic or lifestyle-based predisposition to obesity.
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Shin-Bum
authors.initials: SB
authors.lastname: Jo
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Anthony I
authors.initials: AI
authors.lastname: Romer
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lim
authors.affiliation: Division of Life Sciences, Korea University, Seoul, Republic of Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Division of Life Sciences, Korea University, Seoul, Republic of Korea.
authors.forename: Seung-Hoi
authors.initials: SH
authors.lastname: Koo
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY kangj01@skku.edu robert.krauss@mssm.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Krauss
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Republic of Korea kangj01@skku.edu robert.krauss@mssm.edu.
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Kang
mesh_terms: D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D050177:Overweight / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C510745:Boc protein, mouse; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface