title: Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect.
abstract: Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ) was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107) of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control) and TP5 (tumor + PGZ/5 mg). Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT) depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group). The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01) when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01) on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05) and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT) mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-γ, adiponectin, LPL and C/EBP-α from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT) was entirely re-established due to PGZ treatment. Taken together, the results demonstrate beneficial effects of PGZ treatment at both the early and final stages of cachexia.
authors: Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil.
authors: Mércia
authors: M
authors: Beluzi
authors: Department of Physiological Sciences, State University of Maringá, Paraná, Brazil.
authors: Sidney B
authors: SB
authors: Peres
authors: Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil.
authors: Felipe S
authors: FS
authors: Henriques
authors: Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil; Laboratory of Physiology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
authors: Rogério A L
authors: RA
authors: Sertié
authors: Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil.
authors: Felipe O
authors: FO
authors: Franco
authors: Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil.
authors: Kaltinaitis B
authors: KB
authors: Santos
authors: Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil.
authors: Pâmela
authors: P
authors: Knobl
authors: Laboratory of Physiology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
authors: Sandra
authors: S
authors: Andreotti
authors: Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil; Department of Biomedical Engineering, Federal University of Sao Paulo, Sao Jose dos Campos, Brazil.
authors: Cláudio S
authors: CS
authors: Shida
authors: Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil; Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
authors: Rodrigo X
authors: RX
authors: Neves
authors: Department of Biochemistry, Boston School of Medicine, Boston, Massachusetts, United States of America.
authors: Stephen R
authors: SR
authors: Farmer
authors: Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
authors: Marília
authors: M
authors: Seelaender
authors: Laboratory of Physiology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
authors: Fábio B
authors: FB
authors: Lima
authors: Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil; Cancer Metabolism Research Group, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
authors: Miguel L
authors: ML
authors: Batista
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002100:Cachexia / Q000473:pathology; D002279:Carcinoma 256, Walker / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D004435:Eating / Q000187:drug effects; D008297:Male; D047495:PPAR gamma / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D052242:Adiponectin; D022762:CCAAT-Enhancer-Binding Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone