title: Adipose-specific Vdr deletion alters body fat and enhances mammary epithelial density.
abstract: Vitamin D status has been associated with obesity, metabolic syndrome and several cancers including colon and breast. Since adipocytes express VDR and obesity is a known risk factor for cancer, vitamin D actions in adipose tissue may contribute to its cancer protective effects. In the mammary gland, signaling from adipocytes to epithelial cells is necessary for breast cancer initiation, but the impact of vitamin D on this cross-talk is unclear. To examine the role of VDR in adipose tissue, particularly in the context of the mammary gland, we crossed Vdr-flox mice with Fabp4-cre mice to generate mice with adipose-specific Vdr deletion (termed CVF mice). CVF mice and Fabp4-cre control mice (termed CN1 mice) were reared on high calcium "rescue" diets (for comparison to global VDRKO mice) or on high fat diets (to stimulate adiposity). Vdr expression was significantly reduced in adipose tissue of CVF mice compared to CN1 mice. In contrast to global VDRKO mice (which exhibit adipose atrophy), female CVF mice exhibited higher growth rates and increased visceral fat pad weight compared to control mice. Expression of Ucp1 and Pparg were elevated in white adipose tissue of CVF mice supporting these genes as Vdr targets in mature adipocytes. Adipose-specific Vdr deletion did not impair glucose tolerance or alter the weight of brown adipose tissue, liver, pancreas or bone in response to high fat feeding. In contrast to the effect of adipose-specific Vdr deletion on visceral fat pads, the weight of the subcutaneous (mammary) fat pad was not increased in high fat fed CVF female mice compared to control mice. Quantitative analysis of mammary ductal development on whole mounts and H&E stained sections indicated that adipose-deletion of Vdr significantly enhanced mammary epithelial density and branching. Collectively, these data support the hypothesis that Vdr in mature adipocytes alters the metabolic response to high fat diets and exerts anti-proliferative effects on the mammary epithelium.
authors.affiliation: University at Albany Cancer Research Center, Rensselaer, NY 12144, United States.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Matthews
authors.affiliation: University at Albany Cancer Research Center, Rensselaer, NY 12144, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: D'Angelo
authors.affiliation: University at Albany Cancer Research Center, Rensselaer, NY 12144, United States.
authors.forename: Jordan
authors.initials: J
authors.lastname: Drelich
authors.affiliation: University at Albany Cancer Research Center, Rensselaer, NY 12144, United States. Electronic address: jwelsh@albany.edu.
authors.forename: JoEllen
authors.initials: J
authors.lastname: Welsh
mesh_terms: D052438:Adipocytes, White / Q000378:metabolism* / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D059305:Diet, High-Fat; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction; D000071256:Uncoupling Protein 1 / Q000235:genetics / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism
chemical_list: C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D018167:Receptors, Calcitriol; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D014807:Vitamin D; C045073:Cre recombinase; D019426:Integrases
keywords: Adipose; Mammary gland; VDR; Vitamin D; Western-style diet