Effect of tirzepatide-induced weight loss on adipose tissue in obesity: rationale and design of the randomized placebo-controlled Tirzepatide Brown and Beige Adipose Tissue Activation (TABFAT) trial.
Rok Herman, Mojca Jensterle, Simon Horvat, Luka Lezaic, Ziga Snoj, Igor Pusnik, Katja Goricar, Andrej Cör, Luka Pusnik, Vid Mlacnik, Lara Hanzelic, Andrej Janez
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Abstract
Background: Obesity is a complex disease marked by excessive, dysfunctional adipose tissue accumulation. Recent research underscores the pivotal role of brown adipose tissue (BAT) in metabolic health and its potential as a therapeutic target for obesity management. Emerging preclinical and clinical evidence suggests that second-generation anti-obesity drugs, especially dual agonists such as tirzepatide, may enhance BAT activity. Additionally, beige adipose tissue, derived from white adipose tissue (WAT), may contribute significantly to whole-body thermogenesis, yet its role remains underexplored.
Methods: This investigator-initiated, randomized, placebo-controlled clinical trial aims to evaluate the effects of tirzepatide on BAT activity and WAT browning in premenopausal women with obesity. Thirty-four participants will be randomized 1:1 to receive either tirzepatide or a placebo for 24 weeks. Primary outcomes include changes in BAT volume and activity, assessed using 18F-FDG-PET/CT, MRI, and infrared thermography, as well as the induction of WAT browning, evaluated through changes in mRNA expression patterns and histomorphometric alterations in subcutaneous adipose tissue samples. Secondary outcomes will involve the assessment of whole-body composition, resting energy expenditure, and various metabolic health markers, correlated with thermogenic adipose tissue changes. Comparative analysis of BAT assessment methods will refine protocols for research and clinical use.
Discussion: This study is the first to systematically explore the potential of pharmacological obesity management to enhance BAT activity and induce WAT browning. Results may establish thermogenic adipose tissue augmentation as a novel mechanism of action for second-generation anti-obesity medications.
Trial registration: ClinicalTrials.gov NCT06893211. Registered on 2025 March 25.
期刊介绍：
Trials is an open access, peer-reviewed, online journal that will encompass all aspects of the performance and findings of randomized controlled trials. Trials will experiment with, and then refine, innovative approaches to improving communication about trials. We are keen to move beyond publishing traditional trial results articles (although these will be included). We believe this represents an exciting opportunity to advance the science and reporting of trials. Prior to 2006, Trials was published as Current Controlled Trials in Cardiovascular Medicine (CCTCVM). All published CCTCVM articles are available via the Trials website and citations to CCTCVM article URLs will continue to be supported.
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