title: Administration of granulocyte-colony stimulating factor accompanied with a balanced diet improves cardiac function alterations induced by high fat diet in mice.
abstract: OBJECTIVE
  High fat diet (HFD) is a major contributor to the development of obesity and cardiovascular diseases due to the induction of cardiac structural and hemodynamic abnormalities. We used a model of diabetic cardiomyopathy in C57Bl/6 mice fed with a HFD to investigate the effects of granulocyte-colony stimulating factor (G-CSF), a cytokine known for its beneficial effects in the heart, on cardiac anatomical and functional abnormalities associated with obesity and type 2 diabetes.
  
  
  METHODS
  Groups of C57Bl/6 mice were fed with standard diet (n = 8) or HFD (n = 16). After 36 weeks, HFD animals were divided into a group treated with G-CSF + standard diet (n = 8) and a vehicle control group + standard diet (n = 8). Cardiac structure and function were assessed by electrocardiography, echocardiography and treadmill tests, in addition to the evaluation of body weight, fasting glicemia, insulin and glucose tolerance at different time points. Histological analyses were performed in the heart tissue.
  
  
  RESULTS
  HFD consumption induced metabolic alterations characteristic of type 2 diabetes and obesity, as well as cardiac fibrosis and reduced exercise capacity. Upon returning to a standard diet, obese mice body weight returned to non-obese levels. G-CSF administration accelerated the reduction in of body weight in obese mice. Additionally, G-CSF treatment reduced insulin levels, diminished heart fibrosis, increased exercise capacity and reversed cardiac alterations, including bradycardia, elevated QRS amplitude, augmented P amplitude, increased septal wall thickness, left ventricular posterior thickening and cardiac output reduction.
  
  
  CONCLUSIONS
  Our results indicate that G-CSF administration caused beneficial effects on obesity-associated cardiac impairment.
authors.affiliation: Center for Biotechnology and Cell Therapy, Hospital Sao Rafael, Salvador, BA, Brazil. ps.daltro@yahoo.com.br.
authors.forename: Pâmela Santana
authors.initials: PS
authors.lastname: Daltro
authors.affiliation: Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (CPqGM/FIOCRUZ), Salvador, BA, Brazil. paula.s.alves@hotmail.com.
authors.forename: Paula Santana
authors.initials: PS
authors.lastname: Alves
authors.affiliation: Center for Biotechnology and Cell Therapy, Hospital Sao Rafael, Salvador, BA, Brazil. fagundescastro@yahoo.com.br.
authors.forename: Murilo Fagundes
authors.initials: MF
authors.lastname: Castro
authors.affiliation: Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (CPqGM/FIOCRUZ), Salvador, BA, Brazil. cariazevedo@hotmail.com.
authors.forename: Carine M
authors.initials: CM
authors.lastname: Azevedo
authors.affiliation: Federal University of Bahia, Salvador, BA, Brazil. julianafvs@gmail.com.
authors.forename: Juliana Fraga
authors.initials: JF
authors.lastname: Vasconcelos
authors.affiliation: Center for Biotechnology and Cell Therapy, Hospital Sao Rafael, Salvador, BA, Brazil. kyan.allahdadi@gmail.com.
authors.forename: Kyan James
authors.initials: KJ
authors.lastname: Allahdadi
authors.affiliation: Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (CPqGM/FIOCRUZ), Salvador, BA, Brazil. lfreitas@bahia.fiocruz.br.|Federal University of Bahia, Salvador, BA, Brazil. lfreitas@bahia.fiocruz.br.
authors.forename: Luiz Antônio Rodrigues
authors.initials: LA
authors.lastname: de Freitas
authors.affiliation: Center for Biotechnology and Cell Therapy, Hospital Sao Rafael, Salvador, BA, Brazil. brunosolanosouza@gmail.com.|Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (CPqGM/FIOCRUZ), Salvador, BA, Brazil. brunosolanosouza@gmail.com.
authors.forename: Bruno Solano
authors.initials: BS
authors.lastname: de Freitas Souza
authors.affiliation: Center for Biotechnology and Cell Therapy, Hospital Sao Rafael, Salvador, BA, Brazil. ricardoribeiro@cbtc-hsr.org.
authors.forename: Ricardo Ribeiro
authors.initials: RR
authors.lastname: Dos Santos
authors.affiliation: Center for Biotechnology and Cell Therapy, Hospital Sao Rafael, Salvador, BA, Brazil. milena@bahia.fiocruz.br.|Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (CPqGM/FIOCRUZ), Salvador, BA, Brazil. milena@bahia.fiocruz.br.
authors.forename: Milena Botelho Pereira
authors.initials: MB
authors.lastname: Soares
authors.affiliation: Center for Biotechnology and Cell Therapy, Hospital Sao Rafael, Salvador, BA, Brazil. simone@bahia.fiocruz.br.|Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (CPqGM/FIOCRUZ), Salvador, BA, Brazil. simone@bahia.fiocruz.br.|Federal University of Bahia, Salvador, BA, Brazil. simone@bahia.fiocruz.br.
authors.forename: Simone Garcia
authors.initials: SG
authors.lastname: Macambira
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005355:Fibrosis; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006439:Hemodynamics; D007328:Insulin / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D009765:Obesity / Q000150:complications* / Q000473:pathology / Q000503:physiopathology
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D016179:Granulocyte Colony-Stimulating Factor; D002784:Cholesterol