title: Partial lipectomy reduces dimethylhydrazine-induced carcinogenic initiation in the colon of rats.
abstract: This study investigated whether visceral adipose tissue directly modulates the development of preneoplastic lesions in the colon of carcinogen-treated rats. Wistar rats (n=64) were randomly assigned to 8 experimental groups in two experiments. In one experiment, 32 rats were exposed or not to either carcinogen treatment (dimethylhydrazine, DMH; 125 mg/kg) or high-fat diet (standard chow enriched with 14% lard) or both for 56 days. In a second experiment, 32 rats were exposed to a carcinogen or they underwent partial lipectomy or both for 30 days (partial lipectomy groups underwent ablation of mesenteric and parametrial fat pads, whereas sham groups did not; all rats were fed with standard chow). Colon was collected for histopathological analysis. After 56 experimental days a high-fat diet increased carcinogenic mutations in the colonic epithelia. Partial lipectomy reduced weight gain in carcinogen-exposed rats and decreased the de novo formation of mesenteric and parametrial fat pads. Partial lipectomy significantly inhibited the mutational process after 30 days: there were fewer colonic preneoplastic lesions and less proliferation, apoptosis, and inflammation. These data suggest that visceral adipose tissue promotes colon carcinogenesis and enhances the establishment and expansion of genetically mutated cells in colonic epithelia.
authors.affiliation: Department of Surgery I, Molecular Oncology and Immunology, University of Wuerzburg, Germany. Electronic address: vinicius.cardoso@uni-wuerzburg.de.
authors.forename: Vinicius
authors.initials: V
authors.lastname: Kannen
authors.affiliation: Department of Pathology, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Mauro César Silveira
authors.initials: MC
authors.lastname: Moreira
authors.affiliation: Department of Surgery I, Molecular Oncology and Immunology, University of Wuerzburg, Germany.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Waaga-Gasser
authors.affiliation: Department of Pathology, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Modiano
authors.affiliation: Radiology Division, Medical School of Ribeirão Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Elias Junior
authors.affiliation: Department of Pathology, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Cleverson R
authors.initials: CR
authors.lastname: Fernandes
authors.affiliation: Department of Pathology, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Sérgio B
authors.initials: SB
authors.lastname: Garcia
mesh_terms: D000818:Animals; D017209:Apoptosis; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D059305:Diet, High-Fat / Q000009:adverse effects; D004127:Dimethylhydrazines / Q000633:toxicity*; D005260:Female; D007249:Inflammation / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000601:surgery; D015187:Lipectomy / Q000379:methods; D008297:Male; D009154:Mutation; D011230:Precancerous Conditions / Q000473:pathology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002273:Carcinogens; D004127:Dimethylhydrazines
keywords: Aberrant crypt foci; Apoptosis; Colon carcinogenesis; Partial lipectomy; Proliferation