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Impact of different ectopic fat depots on cardiovascular and metabolic diseases
Abstract
A growing body of evidence is pointing out the pathophysiological role of fat accumulation in different organs. Ectopic fat depots within heart, liver, skeletal muscle, kidney, and pancreas as well as around blood vessels might be more associated to cardiometabolic risk than classical variables, such as body mass index. Among different mechanisms, lipid metabolism appears to be particularly influenced by ectopic fat depots. Indeed, intracellular accumulation of nonesterified fatty acids, and triglycerides promotes endoplasmic reticulum stress, mitochondrial uncoupling, oxidative stress, and altered membrane composition/function, finally promoting inflammatory response and cell death. The dysfunctional adipose tissue was shown to induce both local and systemic effects, with relevant clinical consequences. Epicardial fat and myocardial steatosis have been associated with the development of atrial fibrillation and ventricular dysfunction. Similarly perivascular adipose tissue appears to trigger atherosclerosis and hypertension. Nonalcoholic fatty liver disease has been recognized both as the hepatic manifestation of metabolic syndrome and as a cardiovascular (CV) risk factor. Importantly, the renal sinus fat emerged as a potential player in kidney dysfunction. Finally, both skeletal muscle and pancreatic fat depots have been indicated as potential endocrine modulators of insulin resistance. Considering the global rise in the prevalence of obesity, the understanding of mechanisms underlying ectopic fat accumulation represents an urgent need, with potential clinical implications for CV risk stratification. Here, we attempt to update the current knowledge of the different ectopic fat depots, focusing on underlying mechanisms and potential clinical implications.
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“The consequent heart overfeeding may promote a myocardial steatosis that has been associated with the development of ventricular dysfunction [87].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [87]
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“However, while ectopic fat in skeletal muscles is often associated withmetabolic disease, highly trained athletes have been reported to have comparable amounts of skeletal muscle fat as subjects with T2DM, yet their tissue remains highly insulin sensitive (323).”
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“These lipid mediators have been associated with the activation of the inflammatory response, ROS production, mitochondrial dysfunction, autophagy deregulation, endoplasmic reticulum stress (ER stress) and apoptosis [69,80,81].”
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“SIRI has received much attention recently as its significant role in predicting patient outcomes has been documented in diseases such as cancer,(33) infectious diseases,(34) and cardiovascular disease.(35) However, to the best of our knowledge, no study has assessed the role of SIRI in predicting post-stroke mortality.”
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Metadata
- Authors
- Ferrara, D., Montecucco, F., Dallegri, F., & Carbone, F.
- Affiliations
- University of Genoa (IT)
- Ospedale Policlinico San Martino (IT)
- Corresponding author
- Carbone, Federico
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2019-05-20
- Volume
- 234
- Issue
- 12
- Pages
- 21630-21641
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- OpenAlex
- W2944904922
- Cited by
- 195
- References
- 140
- Citations by year
- 2026: 20 · 2025: 23 · 2024: 19 · 2023: 32 · 2022: 22 · 2021: 36 · 2020: 29 · 2019: 13
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Funders
- Ministero della Salute
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- cardiometabolic risk, epicardial adipose tissue, myocardial steatosis, perivascular adipose tissue, non-alcoholic fatty liver disease, renal sinus fat, skeletal muscle fat, pancreatic fat, insulin resistance, lipid metabolism, endoplasmic reticulum stress, mitochondrial uncoupling, oxidative stress, inflammation, atrial fibrillation, ventricular dysfunction, atherosclerosis, hypertension, obesity
- MeSH terms
- Adipose Tissue, Animals, Cardiovascular Diseases, Fats, Humans, Liver, Metabolic Diseases, Body Mass Index
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