REVIEW article
Front. Endocrinol.
Sec. Obesity
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1592683
This article is part of the Research TopicExploring the Dynamics of Tissue Flexibility: Molecular Changes and Their Implications for Metabolic DisordersView all 5 articles
Adipose Tissue Dysfunction Disrupts Metabolic Homeostasis: Mechanisms Linking Fat Dysregulation to Disease
Provisionally accepted
Dana Bou Matar1
Mahmoud Zhra2
Walid Khaled Nassar3
Haifa Altemyatt3Asfiya Naureen3Nada Abotouk3
Muhammad Elahi3
Ahmad ALJADA2*- 1Department of Physiological Sciences, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- 2Department of Biochemistry & Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- 3College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
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Background: Metabolic disease incidence continues rising globally. Adipose tissue dysfunction serves as a crucial pathophysiological mediator. We evaluate molecular mechanisms linking adipose dysfunction to metabolic dysregulation. Methods: We systematically reviewed literature on adipose biology, stress mechanisms, inflammation, and metabolic networks. Analysis prioritized methodologically robust studies from the past decade. Results: Adipose dysfunction disrupts metabolic homeostasis through complex molecular networks. Stressed adipocytes exhibit mitochondrial impairment and endoplasmic reticulum (ER) stress. These changes alter inflammatory mediators and adipokine secretion. Brown and beige adipose regulate energy balance via uncoupling protein 1 (UCP1)-mediated thermogenesis. Key transcriptional regulators, PGC-1α and PR domain containing 16 (PRDM16), control thermogenic adipocyte development. Cellular senescence contributes significantly to age-related adipose dysfunction through inflammatory secretory phenotypes. Brown fat also secretes specialized factors influencing whole-body metabolism, emphasizing adipose tissue's endocrine function. Conclusion: Adipose dysfunction represents a critical nexus in metabolic disease pathogenesis. Cellular stress, inflammation, and metabolic dysregulation converge at this point. Novel therapies targeting thermogenic activation and cellular senescence show promise. Despite advancing mechanistic understanding, developing effective interventions remains challenging due to adipose tissue's complex roles in systemic metabolic regulation.
Keywords: Conceptualization, resources, supervision, Validation, Writingoriginal draft, Writingreview & editing. Asfiya Naureen: Investigation, Writingreview & editing. Dana Bou Matar: Conceptualization, Literature analysis
Received: 12 Mar 2025; Accepted: 02 Jun 2025.
Copyright: © 2025 Bou Matar, Zhra, Nassar, Altemyatt, Naureen, Abotouk, Elahi and ALJADA. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ahmad ALJADA, Department of Biochemistry & Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, 11533, Saudi Arabia
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.