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

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...

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Bibliographic Details
Published in:Acta diabetologica 2019-12, Vol.56 (12), p.1333-1339
Main Authors: de-Lima-Júnior, José C., Rodovalho, Sylka, Van de Sande-Lee, Simone, Monfort-Pires, Milena, Rachid, Briana, Cintra, Riobaldo M., Ramos, Celso D., Cendes, Fernando, Folli, Franco, Velloso, Lício A.
Format: Article
Language:English
Subjects:
Adipose tissue (brown)
Adipose Tissue, Brown - diagnostic imaging
Adipose Tissue, Brown - drug effects
Adipose Tissue, Brown - pathology
Adult
Aged
Body mass
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - diagnosis
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - pathology
Drug Therapy, Combination
Female
Fluorodeoxyglucose F18
Gliosis
Gliosis - diagnosis
Gliosis - pathology
Gliosis - prevention & control
Humans
Hypothalamus
Hypothalamus - diagnostic imaging
Hypothalamus - drug effects
Hypothalamus - pathology
Internal Medicine
Magnetic resonance imaging
Male
Medicine
Medicine & Public Health
Menopause
Metabolic Diseases
Metabolic disorders
Middle Aged
Obesity - complications
Obesity - diagnosis
Obesity - drug therapy
Obesity - pathology
Organ Size - drug effects
Original Article
Overweight - complications
Overweight - diagnosis
Overweight - drug therapy
Overweight - pathology
Patients
Pioglitazone
Pioglitazone - administration & dosage
Pioglitazone - pharmacology
Positron emission tomography
Positron Emission Tomography Computed Tomography
Proof of Concept Study
Structure-function relationships
Thiazolidinediones - administration & dosage
Thiazolidinediones - pharmacology
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Summary: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 18 F-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.
ISSN:0940-5429
1432-5233
DOI:10.1007/s00592-019-01418-2