Cited by 2,814Adipokines, Inflammation, and Metabolic DiseasesCardiovascular Disease and AdiposityDiabetes, Cardiovascular Risks, and Lipoproteins

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Mechanisms linking obesity with cardiovascular disease

Van Gaal, Luc F., Mertens, Ilse L., De Block, Christophe E.·2006·Nature

DOI 10.1038/nature05487

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Abstract

Obesity increases the risk of cardiovascular disease and premature death. Adipose tissue releases a large number of bioactive mediators that influence not only body weight homeostasis but also insulin resistance - the core feature of type 2 diabetes - as well as alterations in lipids, blood pressure, coagulation, fibrinolysis and inflammation, leading to endothelial dysfunction and atherosclerosis. We are now beginning to understand the underlying mechanisms as well as the ways in which smoking and dyslipidaemia increase, and physical activity attenuates, the adverse effects of obesity on cardiovascular health.

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Background
Intra-abdominal fat is related to metabolic syndrome and non-alcoholic fat liver disease in obese youth
Silveira, L. S., Monteiro, P. A., Antunes, B. M., Seraphim, P. M., Fernandes, R. A., Christófaro, D. G. D., & Júnior, I. F. F. (2013) · BMC Pediatrics · doi:10.1186/1471-2431-13-115 · Cited by 61
“Adipose tissue has an endocrine function that produces multiple adipokines causing inflammatory process and insulin resistance [4,23,24].”
BackgroundResult
Assessment of Endothelial Dysfunction in Childhood Obesity and Clinical Use
Bruyndonckx, L., Hoymans, V. Y., Craenenbroeck, A. H. V., Vissers, D. K., Vrints, C. J., Ramet, J., & Conraads, V. M. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/174782 · Cited by 66
“…been thought that storage and release of free fatty acids were its only functions, adipose tissue is currently seen as an important endocrine organ, regulating glucose and lipid metabolism and producing a vast amount of cytokines (adipocyte-derived cytokines or adipokines) and hormones [49, 50].”
Background
The Systemic Inflammome of Severe Obesity before and after Bariatric Surgery
Arismendi, E., Rivas, E., Agustí, A. G. N., Ríos, J., Barreiro, E., Vidal, J., & Rodriguez‐Roisin, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107859 · Cited by 64
“In addition, external risk factors such as smoking often contribute to enhance the adverse effects of obesity on cardiovascular health [3].”
Background
An Inhibitor of Phospholipase A2 Group IIA Modulates Adipocyte Signaling and Protects Against Diet-Induced Metabolic Syndrome in Rats
Iyer, A., Lim, J., Poudyal, H., Reid, R. C., Suen, J. Y., Webster, J. A., Prins, J. B., Whitehead, J. P., Fairlie, D. P., & Brown, L. (2012) · Diabetes · doi:10.2337/db11-1179 · Cited by 61
Impact of body composition during weight change on resting energy expenditure and homeostasis model assessment index in overweight nonsmoking adults
Pourhassan, M., Bosy‐Westphal, A., Schautz, B., Braun, W., Glüer, C., & Müller, M. J. (2014) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.071829 · Cited by 61
Analysis of Positive Selection at Single Nucleotide Polymorphisms Associated with Body Mass Index Does Not Support the “Thrifty Gene” Hypothesis
Wang, G., & Speakman, J. R. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.014 · Cited by 61
Heritable components of the human fecal microbiome are associated with visceral fat
Roy, C. I. L., Beaumont, M., Jackson, M. A., Steves, C. J., Spector, T. D., & Bell, J. T. (2017) · Gut Microbes · doi:10.1080/19490976.2017.1356556 · Cited by 63
“Obesity leads to increased cancer, cardiovascular and metabolic disease risk.(1) Although overall obesity, as measured by body mass index (BMI) is generally the most commonly used phenotype to assess health implications, it is the accumulation of visceral fat that is the most significant cardio-metabolic disease risk…”
Background
Inhibition of pancreatic lipase by the constituents in St. John's Wort: In vitro and in silico investigations
Hou, X.-D., Guan, X., Cao, Y., Weng, Z.-M., Hu, Q., Liu, H., Jia, S.-N., Zang, S., Zhou, Q., Yang, L., et al. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.12.231 · Cited by 61
Back to the heart: The protective role of adiponectin
Caselli, C., D’Amico, A., Cabiati, M., Prescimone, T., Ry, S. D., & Giannessi, D. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.03.003 · Cited by 61
Study on the mechanism of various exogenous proteins with different inhibitions on wheat starch digestion: From the distribution behaviors of protein in the starch matrix
Zhang, S., Zhu, S., Zhong, F., Huang, D., Chen, X., & Li, Y. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.124909 · Cited by 60
Joint assessment of abdominal obesity and non-traditional lipid parameters for primary prevention of cardiometabolic multimorbidity: insights from the China health and retirement longitudinal study 2011–2018
Lai, H., Tu, Y., Liao, C., Zhang, S., He, L., & Li, J. (2025) · Cardiovascular Diabetology · doi:10.1186/s12933-025-02667-y · Cited by 70
“Conversely, adipose tissue releases a large number of bioactive mediators that not only influence body weight homeostasis and insulin resistance (IR) but also cause alterations in lipids and inflammation, leading to endothelial dysfunction and atherosclerosis [45].”
Inflammatory Cytokines and the Risk of Cardiovascular Complications in Type 2 Diabetes
Mahmoud, F. F., & Al‐Ozairi, E. (2013) · Disease Markers · doi:10.1155/2013/931915 · Cited by 61
Fatty Liver Index Predicts Further Metabolic Deteriorations in Women with Previous Gestational Diabetes
Bozkurt, L., Göbl, C. S., Tura, A., Chmelík, M., Prikoszovich, T., Kosi, L., Wagner, O. F., Roden, M., Pacini, G., Gastaldelli, A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032710 · Cited by 60
“Fibrinogen secretion is predominantly influenced by systematic inflammation, whereas PAI-1 is more related to fat accumulation in the liver than in visceral adipose tissues [29,30].”
Functional analyses reveal the greater potency of preadipocytes compared with adipocytes as endothelial cell activator under normoxia, hypoxia, and TNFα exposure
Mack, I., BelAiba, R. S., Djordjevic, T., Görlach, A., Hauner, H., & Bader, B. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90851.2008 · Cited by 63
RBP4 and THBS2 are serum biomarkers for diagnosis of colorectal cancer
Fei, W., Chen, L., Chen, J., Shi, Q., Zhang, L., Liu, S., Li, L., Zheng, L., & Hu, X. (2017) · Oncotarget · doi:10.18632/oncotarget.21173 · Cited by 60
“RBP4 is an adipocyte-secreted molecule that is elevated in the serum seems to signal the presence of insulin resistance and associated cardiovascular risk factors [31].”
Background
The anti-obesogenic effects of dietary berry fruits: A review
Jiang, H., Zhang, W., Li, X., Xü, Y., Cao, J., & Jiang, W. (2021) · Food Research International · doi:10.1016/j.foodres.2021.110539 · Cited by 60
Characterization of different fat depots in NAFLD using inflammation-associated proteome, lipidome and metabolome
Lovrić, A., Granér, M., Björnson, E., Arif, M., Benfeitas, R., Nyman, K., Ståhlman, M., Pentikäinen, M. O., Lundbom, J., Hakkarainen, A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-31865-w · Cited by 61
Comparison of Innovative and Traditional Cardiometabolic Indices in Estimating Atherosclerotic Cardiovascular Disease Risk in Adults
Huang, Y., Huang, J., Lin, C.-I., Chien, H., Lin, Y., Wang, C.-L., Liang, F., Dai, C., & Chuang, H. (2021) · Diagnostics · doi:10.3390/diagnostics11040603 · Cited by 60
Obesity as a Risk Factor for Accelerated Brain Ageing in First-Episode Psychosis—A Longitudinal Study
McWhinney, S. R., Kolenič, M., Franke, K., Fialová, M., Knytl, P., Matějka, M., Španiel, F., & Hájek, T. (2021) · Schizophrenia Bulletin · doi:10.1093/schbul/sbab064 · Cited by 57
Succination of proteins in diabetes
Frizzell, N., Lima, M., & Baynes, J. (2010) · Free Radical Research · doi:10.3109/10715762.2010.524643 · Cited by 59
Phenolic compounds from cambuci (Campomanesia phaea O. Berg) fruit attenuate glucose intolerance and adipose tissue inflammation induced by a high-fat, high-sucrose diet
Donado-Pestana, C. M., Belchior, T., Festuccia, W. T., & Genovese, M. I. (2014) · Food Research International · doi:10.1016/j.foodres.2014.12.032 · Cited by 59
Endogenous sex hormones and C‐reactive protein in healthy postmenopausal women
Störk, S., Bots, M. L., Grobbee, D. E., & van der Schouw, Y. T. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2008.01946.x · Cited by 59
Increased epicardial fat tissue is a marker of metabolic syndrome in adult patients
Yorgun, H., Canpolat, U., Hazırolan, T., Ateş, A. H., Sunman, H., Dural, M., ŞAHINER, L., Kaya, E. B., Aytemir, K., Tokgözoğlu, L. S., et al. (2011) · International Journal of Cardiology · doi:10.1016/j.ijcard.2011.08.067 · Cited by 60
Postprandial lipemic and inflammatory responses to high-fat meals: a review of the roles of acute and chronic exercise
Teeman, C. S., Kurti, S. P., Cull, B. J., Emerson, S. R., Haub, M. D., & Rosenkranz, S. K. (2016) · Nutrition & Metabolism · doi:10.1186/s12986-016-0142-6 · Cited by 61
“For example, TNF-α concentrations may be increased in participants with greater abdominal adiposity and/or advanced age [47, 48].”
Background
Bacterial bile salt hydrolase: an intestinal microbiome target for enhanced animal health
Geng, W., & Lin, J. (2016) · Animal Health Research Reviews · doi:10.1017/s1466252316000153 · Cited by 61
“Host lipid metabolism, cholesterol, and body weight As children and adults are increasingly becoming overweight and obese, obesity-associated diseases will increase (Kahn et al., 2006; Van Gaal et al., 2006).”
Background
The Spleen: A Hub Connecting Nervous and Immune Systems in Cardiovascular and Metabolic Diseases
Lori, A., Perrotta, M., Lembo, G., & Carnevale, D. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061216 · Cited by 61
Antioxidative Property and Molecular Mechanisms Underlying Geniposide-Mediated Therapeutic Effects in Diabetes Mellitus and Cardiovascular Disease
Li, N., Li, L., Wu, H., & Zhou, H. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/7480512 · Cited by 59
“Obesity, a risk factor for cardiovascular disease, triggers structural and functional alterations in the myocardium [88].”
Multifactorial expression of IL‑6 with update on COVID‑19 and the therapeutic strategies of its blockade (Review)
Niculeț, E., Chioncel, V., Elisei, A. M., Miulescu, M., Buzia, O. D., Nwabudike, L. C., Crăescu, M., Draganescu, M. L., Bujoreanu, F. C., Marinescu, E., et al. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.9693 · Cited by 60
“In the pathophysiology of CVD, IL‑6 plays a causative role, as a marker of inflammation related to cardiovascular risk (46,47) and as a significant proatherogenic cytokine (48).”
BackgroundInfluential
Low serum testosterone and frailty in older men and women
Wu, I., Lin, X., Liu, P.-F., Tsai, W.-L., & Shiesh, S. (2010) · Maturitas · doi:10.1016/j.maturitas.2010.07.010 · Cited by 58
Unsaturated Fatty Acids Improve Atherosclerosis Markers in Obese and Overweight Non-diabetic Elderly Patients
de Oliveira, P. A., Kovacs, C., Moreira, P., Magnoni, D., Saleh, M. H., & Faintuch, J. (2017) · Obesity Surgery · doi:10.1007/s11695-017-2704-8 · Cited by 58
Endothelial dysfunction in obese non-hypertensive children without evidence of sleep disordered breathing
Bhattacharjee, R., Alotaibi, W., Gozal, D., Capdevila, Ó. S., & Gozal, D. (2010) · BMC Pediatrics · doi:10.1186/1471-2431-10-8 · Cited by 58
18F-FDG PET/CT in inflammation of unknown origin: a cost-effectiveness pilot-study
Balink, H., Tan, S. S., Veeger, N. J. G. M., Holleman, F., van Eck‐Smit, B. L. F., Bennink, R. J., & Verberne, H. J. (2015) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-015-3010-0 · Cited by 58
Comparison of Insulin Resistance, Metabolic Syndrome and Adiponectin in Overweight Bipolar Patients Taking Sodium Valproate and Controls
Elmslie, J. L., Porter, R., Joyce, P. R., Hunt, P. J., Shand, B. I., & Scott, R. S. (2009) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/00048670802534341 · Cited by 58
Physical Inactivity and Obesity: Relation to Asthma and Chronic Obstructive Pulmonary Disease?
ten Hacken, N. H. T. (2009) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200907-070dp · Cited by 59
Effects of weight gain and weight loss on regional fat distribution
Singh, P., Somers, V. K., Romero‐Corral, A., Kuniyoshi, F. H. S., Pusalavidyasagar, S. S., Davison, D. E., & Jensen, M. D. (2012) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.033829 · Cited by 62
Role of fat mass and adipokines in chronic kidney disease
Axelsson, J., & Stenvinkel, P. (2008) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e3282f2905f · Cited by 57
Persistent Organochlorine Pollutants in Plasma, Blood Pressure, and Hypertension in a Longitudinal Study
Donat‐Vargas, C., Åkesson, A., Tornevi, A., Wennberg, M., Sommar, J. N., Kiviranta, H., Rantakokko, P., & Bergdahl, I. A. (2018) · Hypertension · doi:10.1161/hypertensionaha.117.10691 · Cited by 58
Developmental programming of offspring adipose tissue biology and obesity risk
Rodgers, A., & Sferruzzi-Perri, A. N. (2021) · International Journal of Obesity · doi:10.1038/s41366-021-00790-w · Cited by 57
“The increased incidence of obesity represents a major health challenge as it increases the risk of developing other noncommunicable diseases, including type 2 diabetes [2], fatty liver disease, [3], cardiovascular diseases [4], and cancer [5].”
Background
Contribution of PGC-1α to Obesity- and Caloric Restriction-Related Physiological Changes in White Adipose Tissue
Kobayashi, M., Deguchi, Y., Nozaki, Y., & Higami, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116025 · Cited by 63
Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals
McWhinney, S. R., Brosch, K., Calhoun, V. D., Crespo‐Facorro, B., Crossley, N. A., Dannlowski, U., Dickie, E. W., Dietze, L. M. F., Donohoe, G. J., du Plessis, S. S., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01616-5 · Cited by 58
Visceral abdominal fat accumulation predicts the progression of noncalcified coronary plaque
Imai, A., Komatsu, S., Ohara, T., Kamata, T., Yoshida, J., Miyaji, K., Takewa, M., & Kodama, K. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2012.03.018 · Cited by 57
“The impact of obesity on CVD has usually been assessed using he body mass index (BMI) [4] but some recent studies suggest that VD risk factors could be predicted more accurately using waist ircumference for abdominal obesity measurements [5].”
BackgroundInfluential

Authors: Van Gaal, L. F., Mertens, I. L., & De Block, C. E.
Affiliations: University of Antwerp (BE)
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2006-12
Volume: 444
Issue: 7121
Pages: 875-880
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature05487
OpenAlex: W1964607854
Cited by: 2,814
References: 86
Citations by year: 2026: 64 · 2025: 97 · 2024: 126 · 2023: 137 · 2022: 151 · 2021: 172 · 2020: 179 · 2019: 204 · 2018: 172 · 2017: 173 · 2016: 168 · 2015: 193 · 2014: 194 · 2013: 152 · 2012: 128
FWCI: 11.30
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: obesity, cardiovascular disease, adipose tissue, adipokines, insulin resistance, type 2 diabetes, dyslipidemia, blood pressure, coagulation, fibrinolysis, inflammation, endothelial dysfunction, atherosclerosis, smoking, physical activity, premature mortality
MeSH terms: Cardiovascular Diseases, Endothelium, Vascular, Humans, Insulin Resistance, Obesity, Oxidative Stress, Adiposity

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Mechanisms linking obesity with cardiovascular disease

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