Effect of pioglitazone treatment on brown adipose tissue volume and activity and hypothalamic gliosis in patients with type 2 diabetes mellitus: a proof-of-concept study

  • José C. de-Lima-Júnior
  • Sylka Rodovalho
  • Simone Van de Sande-Lee
  • Milena Monfort-Pires
  • Briana Rachid
  • Riobaldo M. Cintra
  • Celso D. Ramos
  • Fernando Cendes
  • Franco Folli
  • Lício A. VellosoEmail author
Original Article



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.


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.


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.


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.


Insulin resistance Glucose intolerance Obesity Hypothalamus Brown adipose tissue 


Author’s contributions

JCLJ drafted the first version of the manuscript. JCLJ, FF and LV wrote the manuscript. JCLJ, FF and LV edited and reviewed the manuscript. JCLJ, RMC and MMP performed the statistical analyses, reviewed/edited the manuscript and researched the data. JCLJ and MMP performed PET/CT analysis. CDR performed PET/CT scanning. FC performed MRI scanning and edited partially the manuscript. SVSL performed MRI analysis. LV, SR and BR conceived the design of the study. JCLJ, SR and BR recruited and assisted the patients.


This research was sponsored by GSK (GlaxoSmithKline plc). This research was also supported by the São Paulo Research Foundation (FAPESP 2013/076078).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

The study was approved by the local medical ethical committee of the University of Campinas (Ethics Committee approval CAAE: 32930314.8.0000.5404).

Informed consent

All patients being enrolled into this registry provided written informed consent.

Supplementary material

592_2019_1418_MOESM1_ESM.docx (3.8 mb)
Supplementary material 1 (DOCX 3924 kb)


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  • José C. de-Lima-Júnior
    • 1
    • 2
  • Sylka Rodovalho
    • 1
    • 2
  • Simone Van de Sande-Lee
    • 1
    • 3
  • Milena Monfort-Pires
    • 1
    • 2
  • Briana Rachid
    • 1
    • 2
  • Riobaldo M. Cintra
    • 2
  • Celso D. Ramos
    • 4
  • Fernando Cendes
    • 5
  • Franco Folli
    • 2
    • 6
    • 7
  • Lício A. Velloso
    • 1
    • 2
    Email author
  1. 1.Laboratory of Cell Signaling, Department of Internal MedicineUniversity of Campinas (UNICAMP)CampinasBrazil
  2. 2.Obesity and Comorbidities Research CenterCampinasBrazil
  3. 3.Department of Internal MedicineFederal University of Santa Catarina (UFSC)FlorianópolisBrazil
  4. 4.Department of RadiologyUniversity of CampinasCampinasBrazil
  5. 5.Neuroimaging Laboratory, Department of NeurologyUniversity of CampinasCampinasBrazil
  6. 6.School of Medicine, Endocrinology and Metabolism Dipartimento di Scienze Della SaluteUniversita’ degli Studi di MilanoMilanItaly
  7. 7.Departmental Unit of Diabetes and Metabolic DisordersAzienda Socio-Sanitaria Santi Paolo e CarloMilanItaly

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