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Fatty liver is known to be associated with extra-hepatic diseases including atherosclerotic cardiovascular disease and extra-hepatic cancers, which affect the prognosis and quality of life of the patients. The inter-organ crosstalk is mediated by metabolic abnormalities such as insulin resistance and visceral adiposity. Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed as a new definition for fatty liver. MAFLD is characterized by the inclusion criteria of metabolic abnormality. Therefore, MAFLD is expected to identify patients at high risk of extra-hepatic complications. In this review, we focus on the relationships between MAFLD and multi-organ diseases. We also describe the pathogenic mechanisms of the inter-organ crosstalk.
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http://dx.doi.org/10.3390/nu15051123 | DOI Listing |
Redox Biol
September 2025
National Clinical Research Center for Geriatric Diseases, The Second Medical Center, Chinese PLA General Hospital, 100853, Beijing, China; Institute of Geriatric Medicine, The Second Medical Center, Chinese PLA General Hospital, 100853, Beijing, China.
Small extracellular vesicles (sEVs) critically orchestrate inter-tissue and inter-organ communications and may play essential roles in heart-tumor interaction. However, whether cancer-secreted sEVs affect the progression of doxorubicin-induced cardiotoxicity (DOXIC) via orchestrating the tumor cell-cardiomyocyte crosstalk has not yet been explored. Herein, we reveal that Doxorubicin (DOX)-treated breast cancer cells secrete sEVs (D-BCC-sEVs) that exacerbate DOX-induced ferroptosis of human iPSC-derived cardiomyocytes (hiCMs).
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
July 2025
Dongzhimen Hospital, Beijing University of Chinese Medicine Beijing 100700, China.
With the continuous advancement of medical research, it is increasingly recognized that the human body functions as a highly coordinated complex system, and the development of diseases often involves intricate interactions among multiple subsystems, including organs, tissues, and cells. Conventional pharmacological research, which primarily focuses on isolated subsystems, tends to emphasize direct interactions between drugs and the molecular targets in diseased organs. However, this approach often falls short in addressing the multifaceted challenges posed by complex diseases such as metabolic disorders, autoimmune diseases, cancers, and aging.
View Article and Find Full Text PDFiScience
September 2025
Toxalim, Université de Toulouse, INRAE, ENVT, EI-Purpan, Toulouse, France.
Metabolic dysfunction-associated steatotic liver disease (MASLD), and its more advanced stage metabolic dysfunction-associated steatohepatitis, is the most common chronic liver disease, constituting a major public health issue. Relevant preclinical models are needed to define molecular mechanisms underlying MASLD pathogenesis and evaluate therapeutic approaches. The majority of the lipids accumulating in the liver upon MASLD originate from adipose tissue and appropriate models to study the liver-adipose tissue dialog are also needed.
View Article and Find Full Text PDFBiomolecules
August 2025
Department of Physiology, Pharmacology and Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.
Efficient mitochondrial matrix protein quality control (mPQC), regulated by the mitochondrial matrix protease LONP1, is essential for preserving cardiac bioenergetics, particularly in post-mitotic cardiomyocytes, which are highly susceptible to mitochondrial dysfunction. While cardiac mPQC defects could impair heart function, it remains unclear whether such defects can be mitigated through inter-organ crosstalk by modulating mPQC in extra-cardiac tissues, a potentially valuable strategy given the challenges of directly targeting the heart. To investigate this, we examined two mouse models of haploinsufficiency at young adulthood: a cardiomyocyte-specific heterozygous knockout () and a whole-body heterozygous knockout ().
View Article and Find Full Text PDFJ Intern Med
August 2025
European Kidney Health Alliance, Brussels, Belgium.
This review elucidates the critical role of inter-organ crosstalk in systemic health, focusing on the kidney's interactions with the heart, bone marrow, lung, liver, intestine, bone-vascular, and nervous system. These interactions are vital for maintaining physiological homeostasis and are mediated by hormones, cytokines, and metabolites. The kidney's role in these networks is pivotal, as dysfunction can exacerbate systemic diseases, highlighting the need for integrated therapeutic strategies.
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