Unraveling Adipose Tissue Dysfunction: Molecular Mechanisms, Novel Biomarkers, and Therapeutic Targets for Liver Fat Deposition

Author:

Lopez-Yus Marta123,Hörndler Carlos34,Borlan Sofia5,Bernal-Monterde Vanesa126ORCID,Arbones-Mainar Jose M.1237ORCID

Affiliation:

1. Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, University Hospital Miguel Servet, 50009 Zaragoza, Spain

2. Instituto Aragones de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain

3. Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain

4. Pathology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain

5. General and Digestive Surgery Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain

6. Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain

7. CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, 28029 Madrid, Spain

Abstract

Adipose tissue (AT), once considered a mere fat storage organ, is now recognized as a dynamic and complex entity crucial for regulating human physiology, including metabolic processes, energy balance, and immune responses. It comprises mainly two types: white adipose tissue (WAT) for energy storage and brown adipose tissue (BAT) for thermogenesis, with beige adipocytes demonstrating the plasticity of these cells. WAT, beyond lipid storage, is involved in various metabolic activities, notably lipogenesis and lipolysis, critical for maintaining energy homeostasis. It also functions as an endocrine organ, secreting adipokines that influence metabolic, inflammatory, and immune processes. However, dysfunction in WAT, especially related to obesity, leads to metabolic disturbances, including the inability to properly store excess lipids, resulting in ectopic fat deposition in organs like the liver, contributing to non-alcoholic fatty liver disease (NAFLD). This narrative review delves into the multifaceted roles of WAT, its composition, metabolic functions, and the pathophysiology of WAT dysfunction. It also explores diagnostic approaches for adipose-related disorders, emphasizing the importance of accurately assessing AT distribution and understanding the complex relationships between fat compartments and metabolic health. Furthermore, it discusses various therapeutic strategies, including innovative therapeutics like adipose-derived mesenchymal stem cells (ADMSCs)-based treatments and gene therapy, highlighting the potential of precision medicine in targeting obesity and its associated complications.

Funder

Instituto de Salud Carlos III

Gobierno de Aragón

Publisher

MDPI AG

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