José C de-Lima-Júnior1,2, Sylka Rodovalho1,2, Simone Van de Sande-Lee1,3, Milena Monfort-Pires1,2, Briana Rachid1,2, Riobaldo M Cintra2, Celso D Ramos4, Fernando Cendes5, Franco Folli2,6,7, Lício A Velloso8,9. 1. Laboratory of Cell Signaling, Department of Internal Medicine, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil. 2. Obesity and Comorbidities Research Center, Campinas, São Paulo, Brazil. 3. Department of Internal Medicine, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil. 4. Department of Radiology, University of Campinas, Campinas, São Paulo, 13084-970, Brazil. 5. Neuroimaging Laboratory, Department of Neurology, University of Campinas, Campinas, Brazil. 6. School of Medicine, Endocrinology and Metabolism Dipartimento di Scienze Della Salute, Universita' degli Studi di Milano, Milan, Italy. 7. Departmental Unit of Diabetes and Metabolic Disorders, Azienda Socio-Sanitaria Santi Paolo e Carlo, Via A. Di Rudini, 8, 20143, Milan, Italy. 8. Laboratory of Cell Signaling, Department of Internal Medicine, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil. lavelloso@fcm.unicamp.br. 9. Obesity and Comorbidities Research Center, Campinas, São Paulo, Brazil. lavelloso@fcm.unicamp.br.
Abstract
AIMS: This study aimed to evaluate the effect of pioglitazone on brown adipose tissue function and hypothalamic gliosis in humans. Brown adipose tissue and the hypothalamus are regarded as important potential pharmacological targets to metabolic diseases, and defining the impact of current therapies on their structure and/or function could provide therapeutic advance in this field. METHODS: Six patients with type 2 diabetes were treated for 24 weeks with pioglitazone 30 mg/day as an add-on therapy. Brown adipose tissue glucose uptake and volume were determined using 18F-FDG PET/CT scans; hypothalamic gliosis was determined using MRI scans; blood was collected for hormone and biochemistry measurements. All tests were performed at inclusion and six months after pioglitazone introduction. RESULTS: Pioglitazone treatment led to a significant 3% body mass increase. There were neither changes in cold-induced brown adipose tissue glucose uptake and volume nor changes in hypothalamic gliosis. CONCLUSIONS: This is a proof-of-concept study that provides clinical evidence for a lack of action of a thiazolidinedione, pioglitazone, to promote homogeneous and measurable changes in brown adipose tissue volume and also in hypothalamic gliosis after 6 months of treatment.
AIMS: This study aimed to evaluate the effect of pioglitazone on brown adipose tissue function and hypothalamic gliosis in humans. Brown adipose tissue and the hypothalamus are regarded as important potential pharmacological targets to metabolic diseases, and defining the impact of current therapies on their structure and/or function could provide therapeutic advance in this field. METHODS: Six patients with type 2 diabetes were treated for 24 weeks with pioglitazone 30 mg/day as an add-on therapy. Brown adipose tissue glucose uptake and volume were determined using 18F-FDG PET/CT scans; hypothalamic gliosis was determined using MRI scans; blood was collected for hormone and biochemistry measurements. All tests were performed at inclusion and six months after pioglitazone introduction. RESULTS:Pioglitazone treatment led to a significant 3% body mass increase. There were neither changes in cold-induced brown adipose tissue glucose uptake and volume nor changes in hypothalamic gliosis. CONCLUSIONS: This is a proof-of-concept study that provides clinical evidence for a lack of action of a thiazolidinedione, pioglitazone, to promote homogeneous and measurable changes in brown adipose tissue volume and also in hypothalamic gliosis after 6 months of treatment.
Entities:
Keywords:
Brown adipose tissue; Glucose intolerance; Hypothalamus; Insulin resistance; Obesity
Authors: Cornelia Brendle; Norbert Stefan; Eva Grams; Martin Soekler; Christian la Fougère; Christina Pfannenberg Journal: Sci Rep Date: 2020-12-11 Impact factor: 4.379
Authors: Milena Monfort-Pires; Giulianna Regeni-Silva; Prince Dadson; Guilherme A Nogueira; Mueez U-Din; Sandra R G Ferreira; Marcelo Tatit Sapienza; Kirsi A Virtanen; Licio A Velloso Journal: Front Endocrinol (Lausanne) Date: 2022-07-19 Impact factor: 6.055