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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
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.
Journal Article
Biomaterials science and tissue engineering : principles and methods
\"Provides an encyclopedic coverage of biomaterials science which, at the same time, has enough to interest the biomedical scientists and engineers\"-- Provided by publisher.
Book
SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at
www.covid19cellatlas.org
.
An analysis of single-cell transcriptomics datasets from different tissues shows that
ACE2
and
TMPRSS2
are co-expressed in respiratory, corneal and intestinal epithelial cell populations, and that respiratory expression of
ACE2
is associated with genes involved in innate immunity.
Journal Article
Kidney for Sale by Owner
Over the past decade in the United States, nearly 6,000 people a year have died waiting for organ transplants. In 2003 alone, only 20,000 out of the 83,000 waiting for transplants received them--in anyone's eyes, a tragedy. Many of these deaths could have been prevented, and many more lives saved, were it not for the almost universal moral hand-wringing over the concept of selling human organs. Bioethicist Mark Cherry explores the why of these well-intentioned misperceptions and legislation and boldly deconstructs the roadblocks that are standing in the way of restoring health to thousands of people. If most Americans accept the notion that the market is the most efficient means to distribute resources, why should body parts be excluded? Kidney for Sale by Owner contends that the market is indeed a legitimate—and humane—way to procure and distribute human organs. Cherry stakes the claim that it may be even more just, and more compatible with many Western religious and philosophical traditions, than the current charity-based system now in place. He carefully examines arguments against a market for body parts, including assertions based on the moral views of John Locke, Immanuel Kant, and Thomas Aquinas, and shows these claims to be steeped in myth, oversimplification, and contorted logic. Rather than focusing on purported human exploitation and the irrational \"moral repugnance\" of selling organs, Cherry argues that we should focus on saving lives. Following on the thinking of the philosopher Robert Nozick, he demonstrates that, with regard to body parts, the important core humanitarian values of equality, liberty, altruism, social solidarity, human dignity, and, ultimately, improved health care are more successfully supported by a regulated market rather than by well meant, but misguided, prohibitions.
eBook
Reproductive donation : practice, policy, and bioethics
\"Reproductive donation is the most contentious area of assisted reproduction. Even within Europe there are wide variations in what is permitted in each country. This multidisciplinary book takes a fresh look at the practices of egg, sperm and embryo donation and surrogacy, bringing together ethical analysis and empirical research. New evidence is offered on aspects of assisted reproduction and the families these create, including non-traditional types. One of the key issues addressed is should children be told of their donor origin? If they do learn the identity of their donor, what kinds of relationships may be forged between families, the donor and other donor sibling families? Should donation involve a gift relationship? Is intra-familial donation too close for comfort? How should we understand the growing trend for 'reproductive tourism'? This lively and informed discussion offers new insights into reproductive donation and the resulting donor families\"--Provided by publisher.
Book
Adipose-derived circulating miRNAs regulate gene expression in other tissues
Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue—brown especially—into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic
Fgf21
mRNA and circulating FGF21. This gene regulation can be mimicked by the administration of normal, but not ADicerKO, serum exosomes. Expression of a human-specific miRNA in the brown adipose tissue of one mouse
in vivo
can also regulate its 3′ UTR reporter in the liver of another mouse through serum exosomal transfer. Thus, adipose tissue constitutes an important source of circulating exosomal miRNAs, which can regulate gene expression in distant tissues and thereby serve as a previously undescribed form of adipokine.
Adipose tissue is a major source of circulating exosomal miRNAs, which contribute to the regulation of gene expression in distant tissues and organs.
A novel form of adipokine
Adipose tissue is best known as a site of energy storage, but it also has a role in the regulation of metabolism through the release of cell signalling molecules called adipokines. Here Ronald Kahn and colleagues show that adipose tissue constitutes a major source of circulating exosomal microRNAs (miRNAs), and that these miRNAs are able to regulate gene expression in distant tissues. The miRNAs can therefore be considered to be a form of adipokine.
Journal Article
Connective tissue massage : Bindegewebsmassage according to Dicke
\"In 1929 Germany, physiotherapist Elisabeth Dicke suffered from poor circulation in her right leg, acute back pain, and a host of other ailments. With no medical options offered beyond amputation of the leg, she turned to her own training for help. She began to massage the skin and subcutaneous fascia of the sacral bone and pelvic crest with pulling strokes. After several applications, she experienced less back pain, increased circulation to the leg, and within three months, disappearance of all symptoms. This was the beginning of Dickes systematic, scientifically based treatment method of connective tissue massage (or Bindegewebsmassage), now in wide use throughout the world. In this book, practitioners will get the first detailed, how-to description of connective tissue massage (CTM) {in the English language} including the principles, knowledge, and skills to implement it. Special Features: Begins with the origin and practical benefits of CTM, including its neuroanatomical and neurophysiological basis, Explores the relationship between the sensory, motor, and autonomic nervous systems and the complex reflex mechanisms that are activated by CTM therapy, Describes and illustrates specific stroking techniques that trigger the appropriate neural reflexes in every body segment, Shows how to make a diagnostic assessment based on skin, connective tissue, and muscle zones, Covers the full range of orthopedic, neurological, internal medicine, and gynecologic disorders that can be effectively treated with CTM. Complete with treatment plans, indications and contraindications, and modern medical guidelines, this book is essential for all physical and massage therapists and osteopaths who want to successfully integrate CTM into their practices. It is also a fascinating reference for physicians and other medical professionals who are interested in learning more about this important manual technique.\" --Provided by publisher.
Book
Browning of white fat: agents and implications for beige adipose tissue to type 2 diabetes
Mammalian adipose tissue is traditionally categorized into white and brown relating to their function and morphology: while white serves as an energy storage, brown adipose tissue acts as the heat generator maintaining the core body temperature. The most recently identified type of fat, beige adipocyte tissue, resembles brown fat by morphology and function but is developmentally more related to white. The synthesis of beige fat, so-called browning of white fat, has developed into a topical issue in diabetes and metabolism research. This is due to its favorable effect on whole-body energy metabolism and the fact that it can be recruited during adult life. Indeed, brown and beige adipose tissues have been demonstrated to play a role in glucose homeostasis, insulin sensitivity, and lipid metabolism—all factors related to pathogenesis of type 2 diabetes. Many agents capable of initiating browning have been identified so far and tested widely in humans and animal models including in vitro and in vivo experiments. Interestingly, several agents demonstrated to have browning activity are in fact secreted as adipokines from brown and beige fat tissue, suggesting a physiological relevance both in beige adipocyte recruitment processes and in maintenance of metabolic homeostasis. The newest findings on agents driving beige fat recruitment, their mechanisms, and implications on type 2 diabetes are discussed in this review.
Journal Article