title: Pioglitazone improves insulin sensitivity and reduces weight loss in Walker-256 tumor-bearing rats.
abstract: OBJECTIVE
  The lipogenic effect of pioglitazone (PGZ), an insulin (INS) sensitizer, is well established. However, few studies have evaluated PGZ effects in preventing weight loss in cancer. We investigated PGZ effects, alone or associated with INS, on INS resistance, cachexia and metabolic abnormalities induced by Walker-256 tumor in rats.
  
  
  METHODS
  PGZ (5.0mg·kg-1, oral) or PGZ+INS (NPH, 1.0UI·kg-1, sc), were once-daily administered during 12days, starting on the day inoculation of Walker-256 tumor cells. Rats were separated in small (about 17g) and big (about 30g) tumor-bearing.
  
  
  RESULTS
  Big tumor-bearing rats showed greater cachexia, blood triacylglycerol and free fatty acids and INS resistance. PGZ and PGZ+INS treatments did not change tumor growth and food intake, but reduced several abnormalities such as INS resistance, increased blood free fatty acids, retroperitoneal fat wasting and body weight loss in small tumor-bearing rats. The prevention of retroperitoneal fat wasting did not involve reduction of tumor necrosis factor-α expression increased. In big tumor-bearing rats, PGZ and PGZ+INS treatments reversed the high blood triacylglycerol and free fatty acids levels, but had no effect on other parameters.
  
  
  CONCLUSIONS
  PGZ and PGZ+INS improved INS peripheral sensitivity, possibly by decreasing blood free fatty acids, and reduced fat tissue wasting and body weight loss in small tumor-bearing rats. The results suggest clinical benefits of PGZ in preventing INS resistance, adipose tissue wasting and weight loss when the tumor is small, i.e., in less severe cachexia.
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Flaviane
authors.initials: F
authors.lastname: de Fatima Silva
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Milene
authors.initials: M
authors.lastname: Ortiz-Silva
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Winny Beatriz
authors.initials: WB
authors.lastname: de Souza Galia
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: Cassolla
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Maria Fernanda Rodrigues
authors.initials: MF
authors.lastname: Graciano
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Cassia Thaïs Bussamra Vieira
authors.initials: CT
authors.lastname: Zaia
authors.affiliation: Department of Chemistry, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Dimas
authors.initials: D
authors.lastname: Zaia
authors.affiliation: Department of Physiology and Biophysics, University of São Paulo, 05508-900 São Paulo, PR, Brazil.
authors.forename: Ângelo Rafael
authors.initials: ÂR
authors.lastname: Carpinelli
authors.affiliation: Department of Physiology and Biophysics, University of São Paulo, 05508-900 São Paulo, PR, Brazil.
authors.forename: Francemilson Goulart
authors.initials: FG
authors.lastname: da Silva
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil. Electronic address: hmedri@uel.br.
authors.forename: Helenir Medri
authors.initials: HM
authors.lastname: de Souza
mesh_terms: D000818:Animals; D002100:Cachexia / Q000188:drug therapy*; D007333:Insulin Resistance; D008297:Male; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: Cachexia; Cancer; Hypercatabolism; Insulin resistance; Metabolic changes; Thiazolidinediones