Herman Rok, Jensterle Mojca, Horvat Simon, Lezaic Luka, Snoj Ziga, Pusnik Igor, Goricar Katja, Cör Andrej, Pusnik Luka, Mlacnik Vid, Hanzelic Lara, Janez Andrej
Department for Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, 1000, Slovenia.
Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, 1000, Slovenia.
Trials. 2025 Aug 22;26(1):300. doi: 10.1186/s13063-025-09045-9.
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.
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.
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.
ClinicalTrials.gov NCT06893211. Registered on 2025 March 25.
肥胖是一种复杂的疾病，其特征是功能失调的脂肪组织过度堆积。最近的研究强调了棕色脂肪组织（BAT）在代谢健康中的关键作用及其作为肥胖管理治疗靶点的潜力。新出现的临床前和临床证据表明，第二代抗肥胖药物，尤其是如替尔泊肽这样的双重激动剂，可能会增强BAT活性。此外，源自白色脂肪组织（WAT）的米色脂肪组织可能对全身产热有显著贡献，但其作用仍未得到充分探索。
这项由研究者发起的随机、安慰剂对照临床试验旨在评估替尔泊肽对肥胖绝经前女性BAT活性和WAT褐变的影响。34名参与者将按1:1随机分组，接受替尔泊肽或安慰剂治疗24周。主要结局包括使用18F-FDG-PET/CT、MRI和红外热成像评估的BAT体积和活性变化，以及通过皮下脂肪组织样本中mRNA表达模式的变化和组织形态计量学改变来评估的WAT褐变诱导情况。次要结局将涉及评估全身组成、静息能量消耗以及与产热脂肪组织变化相关的各种代谢健康标志物。对BAT评估方法的比较分析将完善研究和临床应用方案。
本研究首次系统探索了药物性肥胖管理增强BAT活性和诱导WAT褐变的潜力。结果可能会确立产热脂肪组织增加作为第二代抗肥胖药物的一种新作用机制。
ClinicalTrials.gov NCT06893211。于2025年3月25日注册。
