Pioglitazone Treatment Increases Survival and Prevents Body Weight Loss in Tumor-Bearing Animals: Possible Anti-Cachectic Effect

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 anticancer 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 (2x10(7)) 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 -80oC (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-gamma, adiponectin, LPL and C/EBP-alpha 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Mogi das Cruzes, Integrated Grp Biotechnol, Lab Adipose Tissue Biol, Mogi Das Cruzes, BrazilUniv São Paulo, Inst Biomed Sci, Canc Metab Res Grp, São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Physiol Lab, São Paulo, BrazilUniv Estadual Maringa, Dept Physiol Sci, Maringa, Parana, BrazilUniversidade Federal de São Paulo, Dept Biomed Engn, Sao Jose Dos Campos, BrazilBoston Sch Med, Dept Biochem, Boston, MA USAUniversidade Federal de São Paulo, Dept Biomed Engn, Sao Jose Dos Campos, BrazilFAPESP: 2010/51078-1FAPESP: 2008/54091-9FAPESP: 2012/51094-1Web of Scienc

The mechanisms involved in the increased adiposity induced by interruption of regular physical exercise practice

We investigated the effects of physical detraining on lipogenesis/lipolysis and cellularity (apoptosis/adipogenesis) in rat subcutaneous (inguinal; SC) and visceral (retroperitoneal; RP) white adipose depots. Main methods: Three groups of male Wistar rats (6-wk old) were studied: (1) (T) trained for 12 weeks; (2) (D) trained for 8 weeks and detrained for 4 weeks; and (3) (S) age-matched sedentary. Training consisted of treadmill running sessions (1 h/day, 5 days/week, 50-60% maximal race capacity). Key findings: Physical detraining increased glucose oxidation, lipogenesis, and adipocyte size in the SC and RP depots. The number of apoptotic SC adipocytes was reduced by 53% in the T (p < 0.0001) and by 43% in the D (p < 0.001) as compared with S. RP adipocyte apoptosis in the T and D was 9.48% and 10.9% greater compared to the S, respectively (p < 0.05). In the SC stromal vascular fraction (SVF) of D rats, adiponectin, sterol regulatory element binding protein (SREBP)-1c, Peroxisome proliferator-activated receptor gamma (PPAR.), and Perilipin A mRNA expressions were more pronounced than S group, suggesting a more intense adipogenesis. This putative adipogenic effect was not observed in the RP depot. The physical detraining promoted rapid increase in the SC and RP depots however not through the same mechanisms. Significance: Physical detraining induced fat cell hypertrophy (increase of lipogenesis) in both SC and RP whereas hyperplasia (increase of adipogenesis and reduction of apoptosis) was found in SC only. These results indicate the mechanism associated with obesogenic effects of detraining varies with the fat depot222103111CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP449814/2014-92013/13601-2; 2006/60403-