title: Cancer cachexia differentially regulates visceral adipose tissue turnover.
abstract: Cancer cachexia (CC) is a progressive metabolic syndrome that is marked by severe body weight loss. Metabolic disarrangement of fat tissues is a very early event in CC, followed by adipose tissue (AT) atrophy and remodelling. However, there is little information regarding the possible involvement of cellular turnover in this process. Thus, in this study, we evaluated the effect of CC on AT turnover and fibrosis of mesenteric (MEAT) and retroperitoneal (RPAT) adipose tissue depots as possible factors that contribute to AT atrophy. CC was induced by a subcutaneous injection of Walker tumour cells (2 × 107) in Wistar rats, and control animals received only saline. The experimental rats were randomly divided into four experimental groups: 0 days, 4 days, 7 days and 14 days after injection. AT turnover was analysed according to the Pref1/Adiponectin ratio of gene expression from the stromal vascular fraction and pro-apoptotic CASPASE3 and CASPASE9 from MEAT and RPAT. Fibrosis was verified according to the total collagen levels and expression of extracellular matrix genes. AT turnover was verified by measurements of lipolytic protein expression. We found that the Pref1/Adiponectin ratio was decreased in RPAT (81.85%, P < 0.05) with no changes in MEAT compared with the respective controls. CASPASE3 and CASPASE9 were activated on day 14 only in RPAT. Collagen was increased on day 7 in RPAT (127%) and MEAT (4.3-fold). The Collagen1A1, Collagen3A1, Mmp2 and Mmp9 mRNA levels were upregulated only in MEAT in CC. Lipid turnover was verified in RPAT and was not modified in CC. We concluded that the results suggest that CC affects RPAT cellular turnover, which may be determinant for RPAT atrophy.
authors.affiliation: Laboratory of Adipose Tissue BiologyCenter for Integrated Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil.
authors.forename: Felipe de Oliveira
authors.initials: FO
authors.lastname: Franco
authors.affiliation: Laboratory of Adipose Tissue BiologyCenter for Integrated Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil.
authors.forename: Magno Alves
authors.initials: MA
authors.lastname: Lopes
authors.affiliation: Laboratory of Adipose Tissue BiologyCenter for Integrated Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil.
authors.forename: Felipe Dos Santos
authors.initials: FS
authors.lastname: Henriques
authors.affiliation: Cancer Metabolism Research GroupInstitute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Rodrigo Xavier das
authors.initials: RX
authors.lastname: Neves
authors.affiliation: Center for Clinical and Translational ResearchUniversity of Mogi das Cruzes, Mogi das Cruzes, Brazil.
authors.forename: Cesário
authors.initials: C
authors.lastname: Bianchi Filho
authors.affiliation: Laboratory of Adipose Tissue BiologyCenter for Integrated Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil miguelj@umc.br.|Cancer Metabolism Research GroupInstitute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Miguel Luiz
authors.initials: ML
authors.lastname: Batista
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D002100:Cachexia / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D053148:Caspase 3; D053453:Caspase 9
keywords: adipose tissue; apoptosis; cancer cachexia; cellular turnover; extracellular matrix