Impact of different ectopic fat depots on cardiovascular and metabolic diseases

Ferrara, Daniele; Montecucco, Fabrizio; Dallegri, Franco; Carbone, Federico

doi:10.1002/jcp.28821

Cited by 195Cardiovascular Disease and AdiposityAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

Impact of different ectopic fat depots on cardiovascular and metabolic diseases

Ferrara, Daniele, Montecucco, Fabrizio, Dallegri, Franco, Carbone, Federico·2019·Journal of Cellular Physiology

DOI 10.1002/jcp.28821

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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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Heart overfeeding may promote myocardial steatosis that has been associated with the development of ventricular dysfunction.
“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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The Fatty Kidney: Obesity and Renal Disease
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Type 2 diabetes: Does pancreatic fat really matter?
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Renal sinus lipomatosis and body composition in hypertensive, obese rabbits.
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1-Methylnicotinamide ameliorates lipotoxicity-induced oxidative stress and cell death in kidney proximal tubular cells
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White adipose tissue overproduces the lipid-mobilizing factor zinc α2-glycoprotein in chronic kidney disease
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Palmitic Acid-Induced Podocyte Apoptosis via the Reactive Oxygen Species-Dependent Mitochondrial Pathway
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Early and late scanning electron microscopy findings in diabetic kidney disease
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Low density lipoprotein receptor–related protein 1 is upregulated in epicardial fat from type 2 diabetes mellitus patients and correlates with glucose and triglyceride plasma levels
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Pancreatic Ultrastructural Enhancement Due to Telmisartan Plus Sitagliptin Treatment in Diet-Induced Obese C57BL/6 Mice
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Resveratrol prevents renal lipotoxicity in high-fat diet-treated mouse model through regulating PPAR-α pathway
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Obesity, ectopic fat and cardiac metabolism
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Low-dose spironolactone, added to long-term ACE inhibitor therapy, reduces blood pressure and urinary albumin excretion in obese patients with hypertensive target organ damage
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Nonalcoholic Steatohepatitis Score is an Independent Predictor of Right Ventricular Dysfunction in Patients with Nonalcoholic Fatty Liver Disease
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Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation
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Adipose tissue distribution, inflammation and its metabolic consequences, including diabetes and cardiovascular disease
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529 · see citing works
“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).”
Background
Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities
Opazo-Ríos, L., Mas, S., Marín-Royo, G., Mezzano, S., Gómez-Guerrero, C., Moreno, J. A., & Egido, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072632 · Cited by 363 · see citing works
“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].”
Background
The Predictive Role of Systemic Inflammation Response Index (SIRI) in the Prognosis of Stroke Patients
Zhang, Y., Xing, Z., Zhou, K., & Jiang, S. (2021) · Clinical Interventions in Aging · doi:10.2147/cia.s339221 · Cited by 264 · see citing works
“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.”
Nonalcoholic Fatty Liver Disease
Zhao, Y.-C., Zhao, G., Chen, Z., She, Z., Cai, J., & Li, H. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.13419 · Cited by 244 · see citing works
“Specifically, perivascular fat can release proinflammatory cytokines in a paracrine manner, directly accelerating vascular IR and endothelial dysfunction.(55) Renal sinus fat has been reported to be closely associated with an increased risk of hypertension, probably due to its paracrine function on RAS components and…”
Inflammaging as a common ground for the development and maintenance of sarcopenia, obesity, cardiomyopathy and dysbiosis
Livshits, G., & Kalinkovich, A. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100980 · Cited by 239 · see citing works
Managing Atherosclerotic Cardiovascular Risk in Young Adults
Stone, N. J., Smith, S. C., Orringer, C. E., Rigotti, N. A., Návar, A. M., Khan, S. S., Jones, D. W., Goldberg, R. B., Mora, S., Blaha, M. J., et al. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.12.016 · Cited by 250 · see citing works
Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases
Sandireddy, R., Sakthivel, S., Gupta, P., Behari, J., Tripathi, M., & Singh, B. K. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1433857 · Cited by 229 · see citing works
Metabolic syndrome-related kidney injury: a review and update
Lin, L., Tan, W., Pan, X., Tian, E., Wu, Z., & Yang, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.904001 · Cited by 139 · see citing works
AI-based CT Body Composition Identifies Myosteatosis as Key Mortality Predictor in Asymptomatic Adults
Nachit, M., Horsmans, Y., Summers, R. M., Leclercq, I. A., & Pickhardt, P. J. (2023) · Radiology · doi:10.1148/radiol.222008 · Cited by 127 · see citing works
Adipokines and Inflammation: Focus on Cardiovascular Diseases
Feijóo‐Bandín, S., Aragón‐Herrera, A., Moraña‐Fernández, S., Anido‐Varela, L., Tarazón, E., Roselló‐Lletí, E., Portolés, M., Moscoso, I., Gualillo, O., González‐Juanatey, J. R., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207711 · Cited by 123 · see citing works
“Regarding the different adipose tissue depots, chemerin expression in humans has been described in SAT [88], visceral adipose tissue (VAT) [88–90], PVAT [83], and EAT [91,92].”
BackgroundInfluential
Neonicotinoid insecticides exposure cause amino acid metabolism disorders, lipid accumulation and oxidative stress in ICR mice
Yan, S., Meng, Z., Tian, S., Teng, M., Yan, J., Jia, M., Li, R., Zhou, Z., & Zhu, W. (2019) · Chemosphere · doi:10.1016/j.chemosphere.2019.125661 · Cited by 109 · see citing works
Effects of newer antidiabetic drugs on nonalcoholic fatty liver and steatohepatitis: Think out of the box!
Ranjbar, G., Mikhailidis, D. P., & Sahebkar, A. (2019) · Metabolism · doi:10.1016/j.metabol.2019.154001 · Cited by 108 · see citing works
Obesity phenotypes and cardiovascular risk: From pathophysiology to clinical management
Preda, A., Carbone, F., Tirandi, A., Montecucco, F., & Liberale, L. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09813-5 · Cited by 108 · see citing works
“Although not close to myocardial tissue, ectopic fat accumulation in the liver, skeletal muscle, and kidney belong to the central tenets of adiposopathy [172].”
Background
Type 2 Diabetes Remission and Lifestyle Medicine: A Position Statement From the American College of Lifestyle Medicine
Kelly, J. H., Karlsen, M. C., & Steinke, G. (2020) · American Journal of Lifestyle Medicine · doi:10.1177/1559827620930962 · Cited by 100 · see citing works
“38 In these non–adipose tissues caloric excess leads to lipotoxicity, meaning the excess fat (intracellular lipids) stored in these cells inhibits their proper functioning.”
Background
Dietary Bioactive Lipids: A Review on Absorption, Metabolism, and Health Properties
Zhang, Y., Zhang, T., Liang, Y., Jiang, L., & Sui, X. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.1c01369 · Cited by 87 · see citing works
Natural alkaloid and polyphenol compounds targeting lipid metabolism: Treatment implications in metabolic diseases
Cheng, C., Li, Z., Zhao, X., Liao, C., Quan, J., Bode, A. M., Cao, Y., & Luo, X. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.172922 · Cited by 81 · see citing works
Obesity, Cardiorespiratory Fitness, and Cardiovascular Disease
Haidar, A., & Horwich, T. B. (2023) · Current Cardiology Reports · doi:10.1007/s11886-023-01975-7 · Cited by 80 · see citing works
The association between triglyceride-glucose index and the incidence of type 2 diabetes mellitus—a systematic review and dose–response meta-analysis of cohort studies
Pranata, R., Huang, I., Irvan, I., Lim, M. A., & Vania, R. (2021) · Endocrine · doi:10.1007/s12020-021-02780-4 · Cited by 73 · see citing works
Sarcodon aspratus polysaccharides ameliorated obesity-induced metabolic disorders and modulated gut microbiota dysbiosis in mice fed a high-fat diet
Chen, J., Liu, J., Yan, C., Zhang, C., Pan, W., Zhang, W., Lu, Y., Chen, L., & Chen, Y. (2020) · Food & Function · doi:10.1039/c9fo00963a · Cited by 67 · see citing works
Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes
Salvatore, T., Galiero, R., Caturano, A., Vetrano, E., Rinaldi, L., Coviello, F., Di Martino, A., Albanese, G., Colantuoni, S., Medicamento, G., et al. (2022) · Biomolecules · doi:10.3390/biom12020176 · Cited by 62 · see citing works
“The consequent heart overfeeding may promote a myocardial steatosis that has been associated with the development of ventricular dysfunction [87].”
Background
Obesity and dyslipidemia in early life: Impact on cardiometabolic risk
Zeljković, A., Vekić, J., & Stefanovic, A. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155919 · Cited by 66 · see citing works
Status of Mitochondrial Oxidative Phosphorylation during the Development of Heart Failure
Bhullar, S. K., & Dhalla, N. S. (2023) · Antioxidants · doi:10.3390/antiox12111941 · Cited by 55 · see citing works
“Considering the high energy demand of the cardiac excitation–contraction and relaxation cycle, patients with abnormalities in the mitochondrial OXPHOS are at a higher risk of developing heart disease [34,35,44,47].”
Background
Update on Obesity and Cardiovascular Risk: From Pathophysiology to Clinical Management
Gallo, G., Desideri, G., & Savoia, C. (2024) · Nutrients · doi:10.3390/nu16162781 · Cited by 60 · see citing works
The Role of Lonp1 on Mitochondrial Functions during Cardiovascular and Muscular Diseases
Zanini, G., Selleri, V., Malerba, M., Solodka, K., Sinigaglia, G., Nasi, M., Mattioli, A. V., & Pinti, M. (2023) · Antioxidants · doi:10.3390/antiox12030598 · Cited by 49 · see citing works
Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension
Kountouras, J., Papaefthymiou, A., Pοlyzos, S. A., Deretzi, G., Vardaka, E., Soteriades, E. S., Tzitiridou‐Chatzopoulou, M., Gkolfakis, P., Karafyllidou, K., & Doulberis, M. (2021) · Microorganisms · doi:10.3390/microorganisms9112351 · Cited by 49 · see citing works
Hepatoprotective effects of Cassiae Semen on mice with non-alcoholic fatty liver disease based on gut microbiota
Luo, H.-Y., Wu, H., Wang, L., Xiao, S., Lu, Y., Liu, C., Yu, X., Zhang, X., Wang, Z., & Tang, L. (2021) · Communications Biology · doi:10.1038/s42003-021-02883-8 · Cited by 49 · see citing works
The association between triglycerides and ectopic fat obesity: An inverted U-shaped curve
Zou, Y., Sheng, G., Yu, M., & Xie, G. (2020) · PLoS ONE · doi:10.1371/journal.pone.0243068 · Cited by 47 · see citing works
“With regard to ectopic fat, it is defined as extra adipose tissue that appears in locations unrelated to the initial storage of adipose tissue, such as fat storage in the liver and muscle, pericardial fat, perivascular fat and perirenal fat, and liver fat is representative of ectopic fat accumulation [13,14].”
Background
Perivascular Adipose Tissue as an Indication, Contributor to, and Therapeutic Target for Atherosclerosis
Liu, Y., Sun, Y., Hu, C., Liu, J., Gao, A., Han, H., Chai, M., Zhang, J., Zhou, Y., & Zhao, Y. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.615503 · Cited by 46 · see citing works
Lipidomics Revealed Aberrant Metabolism of Lipids Including FAHFAs in Renal Tissue in the Progression of Lupus Nephritis in a Murine Model
Hu, C., Du, Y., Xu, X., Li, H., Duan, Q., Xie, Z., Wen, C., & Han, X. (2021) · Metabolites · doi:10.3390/metabo11030142 · Cited by 46 · see citing works
“In particular, the intracellular accumulation of TAGs could induce endoplasmic reticulum stress and subsequent apoptosis [24].”
Background
Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice
Mishra, S., Sadagopan, N., Sadagopan, N., Dunkerly-Eyring, B. L., Rodriguez, S., Sarver, D. C., Murphy, S. A., Knútsdóttir, H., Knútsdóttir, H., Jani, V., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148798 · Cited by 46 · see citing works
“Reduced hepatic and visceral fat are important, as both are proinflammatory and worsen CMS morbidity (32).”
Background
Epicardial fat and atrial fibrillation: the perils of atrial failure
Poggi, A. L., Gaborit, B., Schindler, T. H., Liberale, L., Montecucco, F., & Carbone, F. (2022) · EP Europace · doi:10.1093/europace/euac015 · Cited by 40 · see citing works
Problems of Pathogenesis and Pathogenetic Therapy of COVID-19 from the Perspective of the General Theory of Pathological Systems (General Pathological Processes)
Gusev, E., Sarapultsev, A., Hu, D., & Черешнев, В. А. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147582 · Cited by 39 · see citing works
Dynamics of Epicardiac Fat and Heart Function in Type 2 Diabetic Patients Initiated with SGLT-2 Inhibitors
Braha, A., Timar, B., Diaconu, L., Lupușoru, R., Vasiluță, L., Sima, A. C., Vlad, A., Munteanu, M., Albai, A., Cipu, D., et al. (2019) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s223629 · Cited by 39 · see citing works
“Also, epicardiac fat depots, known as being associated with insulin resistance and coronary artery disease, have proved to induce diastolic dysfunction as a consequence of its local and systemic neurohormonal effects.(18) From the point of view of the therapeutic management of T2D, SGLT2 inhibitors have proved effecti…”
Background
Insights by which TUDCA is a potential therapy against adiposity
Freitas, I. N., junior, J. A. D. S., de Oliveira, K. M., Alves, B. L., Araújo, T. R., Camporez, J. P., Carneiro, E. M., & Davel, A. P. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1090039 · Cited by 38 · see citing works
“Frontiers in Endocrinology 03 to impaired function in the deposited tissues (50), such as blood vessels and liver (51).”
Background
Aging and atrial fibrillation: A vicious circle
Gao, P., Gao, X., Xie, B., Tse, G., & Liu, T. (2023) · International Journal of Cardiology · doi:10.1016/j.ijcard.2023.131445 · Cited by 38 · see citing works
Impact of Dysfunctional Adipose Tissue Depots on the Cardiovascular System
D'Oria, R., Genchi, V. A., Caccioppoli, C., Calderoni, I., Marrano, N., Biondi, G., Borrelli, A., Gioia, L. D., Giorgino, F., & Laviola, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214296 · Cited by 38 · see citing works
Key Chemokine Pathways in Atherosclerosis and Their Therapeutic Potential
Márquez, A. B., van der Vorst, E. P. C., & Maas, S. L. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10173825 · Cited by 36 · see citing works
“However, the pathophysiological characteristics of PVAT appear to vary upon the metabolic status [85,86] and anatomical location [87].”
Background
Fatty Pancreas-Centered Metabolic Basis of Pancreatic Adenocarcinoma: From Obesity, Diabetes and Pancreatitis to Oncogenesis
Chang, M. (2022) · Biomedicines · doi:10.3390/biomedicines10030692 · Cited by 36 · see citing works
“In obesity, lipid metabolism is influenced by ectopic fat depots, including fatty pancreas [27].”
Background
Physical Exercise Potentially Targets Epicardial Adipose Tissue to Reduce Cardiovascular Disease Risk in Patients with Metabolic Diseases: Oxidative Stress and Inflammation Emerge as Major Therapeutic Targets
Nyawo, T. A., Pheiffer, C., Mazibuko-Mbeje, S. E., Mthembu, S. X. H., Nyambuya, T. M., Nkambule, B. B., Gijsen, H. S., Strijdom, H., Tiano, L., & Dludla, P. V. (2021) · Antioxidants · doi:10.3390/antiox10111758 · Cited by 33 · see citing works
Role of adipokines (omentin and visfatin) in coronary artery disease
Ali, S., Alam, R., Ahsan, H., & Khan, S. (2022) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2022.11.023 · Cited by 32 · see citing works
Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease
Dhalla, N. S., Ošťádal, P., & Tappia, P. S. (2025) · Biomedicines · doi:10.3390/biomedicines13061338 · Cited by 27 · see citing works
Macrophages in the pathophysiology of NAFLD: The role of sex differences
Ministrini, S., Montecucco, F., Sahebkar, A., & Carbone, F. (2020) · European Journal of Clinical Investigation · doi:10.1111/eci.13236 · Cited by 26 · see citing works
Metabolic dysfunction-associated steatotic liver disease (MASLD): Exploring systemic impacts and innovative therapies
Jain, P., Jain, A., Deshmukh, R., Samal, P. K., Satapathy, T., & Ajazuddin, M. (2025) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2025.102584 · Cited by 25 · see citing works
Circulating CRP Levels Are Associated with Epicardial and Visceral Fat Depots in Women with Metabolic Syndrome Criteria
Carbone, F., Lattanzio, S., Minetti, S., Ansaldo, A. M., Ferrara, D., Molina‐Molina, E., Belfiore, A., Elia, E., Pugliese, S., Palmieri, V. O., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20235981 · Cited by 24 · see citing works
“, coronary arteries and myocardium) [10].”
Adipose Tissue Dysfunction in Obesity: Role of Mineralocorticoid Receptor
Parasiliti‐Caprino, M., Bollati, M., Merlo, F. D., Ghigo, E., Maccario, M., & Bo, S. (2022) · Nutrients · doi:10.3390/nu14224735 · Cited by 23 · see citing works
Estetrol prevents Western diet–induced obesity and atheroma independently of hepatic estrogen receptor α
Buscato, M., Davezac, M., Zahreddine, R., Adlanmérini, M., Métivier, R., Fillet, M., Cobraiville, G., Moro, C., Foidart, J., Lenfant, F., et al. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00211.2020 · Cited by 22 · see citing works
The association between Chinese Visceral Adipose Index and coronary heart disease: A cohort study in China
Xie, Y., Zhang, Y., Qin, P., Ping, Z., Wang, C., Peng, X., Chen, H., Zhao, D., Xu, S., Wang, L., et al. (2021) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2021.10.020 · Cited by 22 · see citing works
Risk Factors of Non-alcoholic Fatty Liver Disease in the Iranian Adult Population: A Systematic Review and Meta-analysis
Amini‐Salehi, E., Hassanipour, S., Joukar, F., Daryagasht, A. A., Khosousi, M., Aleali, M. S., Ansar, M. M., Heidarzad, F., Abdzadeh, E., Vakilpour, A., et al. (2023) · Hepatitis Monthly · doi:10.5812/hepatmon-131523 · Cited by 22 · see citing works
Abdominal adipose tissue and type 2 diabetic kidney disease: adipose radiology assessment, impact, and mechanisms
Lu, F., Fan, J., Li, F., Liu, L., Chen, Z., Tian, Z., Zuo, L., & Yu, D. (2023) · Abdominal Radiology · doi:10.1007/s00261-023-04062-1 · Cited by 21 · see citing works
“Moreover, hypertension is also the driver of chronic kidney damage [108, 109].”
The effect of observing religious or faith-based fasting on cardiovascular disease risk factors: A systematic review and meta-analysis
Gholampoor, N., Sharif, A. H., & Mellor, D. D. (2024) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2024.02.002 · Cited by 20 · see citing works
Cell stress management by the mitochondrial LonP1 protease – Insights into mitigating developmental, oncogenic and cardiac stress
Venkatesh, S., & Suzuki, C. K. (2019) · Mitochondrion · doi:10.1016/j.mito.2019.10.004 · Cited by 20 · see citing works
Recent Advances in Studying Age-Associated Lipids Alterations and Dietary Interventions in Mammals
Gille, B., Galuska, C. E., Fuchs, B., & Peleg, S. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.773795 · Cited by 20 · see citing works
Magnetic Resonance Imaging Assessment of Abdominal Ectopic Fat Deposition in Correlation With Cardiometabolic Risk Factors
Zhang, Q., Xie, L., Zhang, H., Liu, J., Zhao, Y., Chen, L., Ju, Y., Chen, A., Wang, N., Song, Q., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.820023 · Cited by 23 · see citing works
“Thus, specific patterns of body fat deposition may confer different cardiometabolic risks (11).”
Background
The Lipid Handling Capacity of Subcutaneous Fat Is Programmed by mTORC2 during Development
Hsiao, W., Jung, S., Tang, Y., Haley, J. A., Li, R., Li, H., Calejman, C. M., Sanchez-Gurmaches, J., Hung, C.-M., Luciano, A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108223 · Cited by 16 · see citing works
“For example, the health risks of metabolic syndrome and cardiovascular events for overweight patients with excessive visceral WAT (VWAT) are higher than for individuals with excess subcutaneous WAT (SWAT) (Ferrara et al., 2019; Lessard and Tchernof, 2012; McLaughlin et al., 2011).”
Abdominal periaortic and renal sinus fat attenuation indices measured on computed tomography are associated with metabolic syndrome
Lee, E. J., Cho, N., Kim, H., Nam, B. D., Jeon, J. S., Noh, H., Han, D. C., Kim, S. H., & Kwon, S. H. (2021) · European Radiology · doi:10.1007/s00330-021-08090-7 · Cited by 18 · see citing works
Pericardial fat and cardiovascular diseases: A systematic review and meta‐analysis
Al-Makhamreh, H. K., Toubasi, A. A., Al‐Harasis, L. M., Albustanji, F. H., Al-Sayegh, T., & Al‐Harasis, S. M. (2023) · Journal of Evidence-Based Medicine · doi:10.1111/jebm.12542 · Cited by 18 · see citing works
Hepatic and Skeletal Muscle Adiposity Are Associated with Diabetes Independent of Visceral Adiposity in Nonobese African-Caribbean Men
Miljkovic, I., Kuipers, A. L., Cvejkus, R., Carr, J. J., Terry, J. G., Thyagarajan, B., Wheeler, V. W., Nair, S., & Zmuda, J. M. (2020) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2019.0097 · Cited by 17 · see citing works
“The effects of each adiposity depot vary according with the site and the extent of accumulation.(14,15) The mechanisms behind observed differences in association of various ectopic fat depots with T2D are still unknown.”
Background
An Isoenergetic Multifactorial Diet Reduces Pancreatic Fat and Increases Postprandial Insulin Response in Patients With Type 2 Diabetes: A Randomized Controlled Trial
Pepa, G. D., Brancato, V., Costabile, G., Salamone, D., Corrado, A., Vitale, M., Cavaliere, C., Mancini, M., Salvatore, M., Luongo, D., et al. (2022) · Diabetes Care · doi:10.2337/dc22-0605 · Cited by 16 · see citing works
Transition of BMI Status From Childhood to Adulthood and Cardiovascular-Kidney-Metabolic Syndrome in Midlife: A 36-Year Cohort Study
Wang, Y., Yang, Y., Chen, J., Du, M., Sun, Y., Wang, D., Jia, H., Hu, G., Man, Z., Zhang, T., et al. (2025) · Diabetes Care · doi:10.2337/dca25-0027 · Cited by 15 · see citing works
Ethnic Differences in Body Fat Deposition and Liver Fat Content in Two UK‐Based Cohorts
Alenaini, W., Parkinson, J. R. C., McCarthy, J. P., Goldstone, A. P., Wilman, H. R., Banerjee, R., Yaghootkar, H., Bell, J. D., & Thomas, E. L. (2020) · Obesity · doi:10.1002/oby.22948 · Cited by 15 · see citing works
“With regard to additional outcomes, assessment of ectopic pancreatic fat was not available in either cohort and would have provided an opportunity to investigate a depot linked to the pathophysiology of metabolic disease (48).”
Background
Palmitic Acid Inhibits Myogenic Activity and Expression of Myosin Heavy Chain MHC IIb in Muscle Cells through Phosphorylation-Dependent MyoD Inactivation
Matsuba, I., Fujita, R., & Iida, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065847 · Cited by 14 · see citing works
“In many in vitro and in vivo experimental settings, PA treatment has been shown to induce inflammatory reactions, mitochondrial dysfunction, and the generation of reactive oxygen species, leading to cellular damage and cell and tissue death [13,15,16].”
Background
CardioMetabolic medicine, one more last step forward
Carbone, F. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab713 · Cited by 14 · see citing works
Quantification of the renal sinus fat and exploration of its relationship with ectopic fat deposition in normal subjects using MRI fat fraction mapping
Zhang, Q., Chen, L., An, Q., Pi, P., Dong, Y.-F., Zhao, Y., Wang, N., Fang, X. L., Pu, R., Song, Q., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1187781 · Cited by 13 · see citing works
“Adipose tissue located in different body compartments may play distinct roles and contribute to comorbidities through unique pathophysiological mechanisms (22).”
Background
Prediction of poststroke cognitive impairment based on the systemic inflammatory response index
Chu, M., Luo, Y., Wang, D., Liu, Z., Niu, H., Wu, X., Wang, Y., Lin, J., Wang, Q., & Zhao, J. (2024) · Brain and Behavior · doi:10.1002/brb3.3372 · Cited by 13 · see citing works
“In recent years, SIRI has received extensive attention for its ability to predict outcomes in diseases like tumors, cardiovascular diseases, and infectious diseases (Ferrara et al., 2019; Hui et al., 2018; Pacheco-Barcia et al., 2020).”
Background
Sodium–Glucose Cotransporter Inhibitors: Cellular Mechanisms Involved in the Lipid Metabolism and the Treatment of Chronic Kidney Disease Associated with Metabolic Syndrome
Cortés-Camacho, F., Zambrano-Vásquez, O. R., Aréchaga-Ocampo, E., Castañeda‐Sánchez, J. I., Gonzaga-Sánchez, J. G., Sánchez-Gloria, J. L., Sánchez‐Lozada, L. G., & Osorio‐Alonso, H. (2024) · Antioxidants · doi:10.3390/antiox13070768 · Cited by 13 · see citing works
“Additionally, metabolic imbalance and the limited capacity of AT to increase proportionally in response to energy storage may lead to ectopic fat distribution in other organs, such as the heart, liver, skeletal muscle, pancreas, and kidney [18].”
Background
Cardiometabolic health, visceral fat and circulating irisin levels: Results from a real-world weight loss study
Miazgowski, T., Kaczmarkiewicz, A., Miazgowski, B., & Kopeć, J. (2021) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01415-1 · Cited by 12 · see citing works
Interventions to Address Cardiovascular Risk in Obese Patients: Many Hands Make Light Work
Visco, V., Izzo, C., Bonadies, D., Feo, F. D., Caliendo, G., Loria, F., Mancusi, C., Chivasso, P., Pietro, P. D., Virtuoso, N., et al. (2023) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd10080327 · Cited by 14 · see citing works
“Among different mechanisms, lipid metabolism is mostly 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, promoting inflammatory…”
Background
Ectopic lipid deposition in muscle and liver, quantified by proton magnetic resonance spectroscopy
Buitinga, M., Veeraiah, P., Haans, F., & Schrauwen‐Hinderling, V. B. (2023) · Obesity · doi:10.1002/oby.23865 · Cited by 12 · see citing works
Which Comes First, Nonalcoholic Fatty Liver Disease or Arterial Hypertension?
Golubeva, J. A., Sheptulina, A. F., Elkina, A. Y., Liusina, E. O., Kiselev, A. R., & Drapkina, O. M. (2023) · Biomedicines · doi:10.3390/biomedicines11092465 · Cited by 12 · see citing works
“Altered adipokine profile characterized by an increase in leptin concentration and a decrease in adiponectin levels was also described in NAFLD, thus indicating an additional common pathophysiological link between NAFLD and AH [78].”
Background
Pancreatic Steatosis as a Risk Factor for Pancreatic Ductal Adenocarcinoma: Pathogenesis and Clinical Implications
Papalamprakopoulou, Z., Dey, P., Frascati, R., & Fountzilas, C. K. (2025) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000832 · Cited by 12 · see citing works
Associations of renal sinus fat with blood pressure and ectopic fat in a diverse cohort of adults
Couch, C. A., Fowler, L. A., Goss, A. M., & Gower, B. A. (2022) · International Journal of Cardiology Cardiovascular Risk and Prevention · doi:10.1016/j.ijcrp.2022.200165 · Cited by 12 · see citing works
Effects of Lifestyle Intervention in Tissue-Specific Lipidomic Profile of Formerly Obese Mice
Dahdah, N., González-Franquesa, A., Samino, S., Gama-Pérez, P., Herrero, L., Perales, J. C., Yanes, Ó., Malagón, M. M., & García-Rovés, P. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073694 · Cited by 12 · see citing works
“The extent of ectopic fat accumulation is significantly linked to the ability of visceral AT to expand [2,57,60].”
Background
MiR-221-3p/222-3p Cluster Expression in Human Adipose Tissue Is Related to Obesity and Type 2 Diabetes
Gentile, A., Lhamyani, S., Clemente‐Postigo, M., Estepa, E., Mesa, M. M., Bermúdez‐Silva, F. J., Rodríguez‐Cañete, A., Tinahones, F. J., Olveira, G., & Bekay, R. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417449 · Cited by 11 · see citing works
“Dysfunctional adipose tissue (AT) has been extensively proven to be involved in the development of these obesity-associated comorbidities [2,3].”
Background
Associations between Body Mass Index and Clinical Outcomes in Acute Myocardial Infarction Supported with Extracorporeal Membrane Oxygenation.
Lee, S. N., Moon, D., Jo, M. S., & Yoo, K. (2020) · PubMed Central · doi:10.6515/acs.202009_36(5).20200519b · Cited by 11 · see citing works
Association between ectopic pancreatic and hepatic fat and metabolic risk factors in children with non‐alcoholic fatty liver disease
Lee, E. H., Kim, J. Y., & Yang, H. R. (2021) · Pediatric Obesity · doi:10.1111/ijpo.12793 · Cited by 11 · see citing works
“NAFLD is considered a hepatic manifestation of MetS, as well as an independent risk factor for cardiovascular disease.(7,43) The present study suggests that PFF may predispose children with NAFLD to HTN.”
Background
Computed Tomography-Estimated Pancreatic Steatosis is Associated with Carotid Plaque in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study from China
Sun, P., Fan, C., Wang, R., Chu, T., Sun, X., Zhang, D., & Du, X. (2021) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s299060 · Cited by 11 · see citing works
“Relationship Between Pancreatic Steatosis and Carotid Plaque Ectopic fat deposition is closely related to atherosclerotic plaque and cardiovascular disease.(23) Pancreatic steatosis is Table 3 Univariate Logistic Regression Models for Carotid Plaque and Hypoechoic Plaque”
Background
Serum Acylglycerols Inversely Associate with Muscle Oxidative Capacity in Severe COPD
Li, R., Adami, A., Chang, C., Tseng, C., Hsiai, T. K., & Rossiter, H. B. (2020) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002441 · Cited by 9 · see citing works
Uncoupling Lipid Synthesis from Adipocyte Development
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Authors: Ferrara, D., Montecucco, F., Dallegri, F., & Carbone, F.
Affiliations: University of Genoa (IT)
Ospedale Policlinico San Martino (IT)
Corresponding author: Carbone, Federico
ORCID: Ferrara, Daniele
Montecucco, Fabrizio
Dallegri, Franco
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
DOI: 10.1002/jcp.28821
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 · 2014: 1
FWCI: 4.52
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology › 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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Impact of different ectopic fat depots on cardiovascular and metabolic diseases

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