Cited by 761Adipokines, Inflammation, and Metabolic DiseasesCardiovascular Disease and AdiposityAdipose Tissue and Metabolism

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Minireview: Adiposity, Inflammation, and Atherogenesis

Lyon, Christopher J., Law, Ronald E., Hsueh, Willa A.·2003·Endocrinology

DOI 10.1210/en.2003-0285

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Abstract

Adipose tissue is a dynamic endocrine organ that secretes a number of factors that are increasingly recognized to contribute to systemic and vascular inflammation. Several of these factors, collectively referred to as adipokines, have now been shown regulate, directly or indirectly, a number of the processes that contribute to the development of atherosclerosis, including hypertension, endothelial dysfunction, insulin resistance, and vascular remodeling. Several adipokines are preferentially expressed in visceral adipose tissue, and the secretion of proinflammatory adipokines is elevated with increasing adiposity. Not surprisingly, approaches that reduce adipose tissue depots, including surgical fat removal, exercise, and reduced caloric intake, improve proinflammatory adipokine levels and reduce the severity of their resultant pathologies. Systemic adipokine levels can also be favorably altered by treatment with several of the existing drug classes used to treat insulin resistance, hypertension, and hypercholesterolemia. Greater understanding of adipokine regulation, however, should result in the design of improved treatment strategies to control disease states associated with increase adiposity, an important outcome in view of the growing worldwide epidemic of obesity.

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“Obesity is linked to chronic inflammation and a number of adipose-related proinflammatory cytokines, so called adipokines, are enhanced in plasma from obese subjects contributing to enhanced inflammatory response in many body organs (21).”
Background
Serum amyloid A: production by human white adipocyte and regulation by obesity and nutrition
Poitou, C., Viguerie, N., Cancello, R., Matteis, R. D., Cinti, S., Štich, V., Coussieu, C., Gauthier, É., Courtine, M., Zucker, J., et al. (2005) · Diabetologia · doi:10.1007/s00125-004-1654-6 · Cited by 180
“Increasing evidence suggests that cytokines released from adipose tissue contribute to the development of complications related to obesity, including metabolic [6, 7] and cardiovascular diseases [8, 9].”
Background
Dietary patterns, body mass index and inflammation: Pathways to depression and mental health problems in adolescents
Oddy, W. H., Allen, K. L., Trapp, G., Ambrosini, G. L., Black, L. J., Huang, R., Rzehak, P., Runions, K., Pan, F., Beilin, L. J., et al. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.01.002 · Cited by 198
Cyclooxygenase-2 and the inflammogenesis of breast cancer
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Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation
Ahmad, R., Al‐Mass, A., Atizado, V., Alhubail, A., Al-Ghimlas, F., Alarouj, M., Bennakhi, A., Dermime, S., & Behbehani, K. (2012) · Journal of Inflammation · doi:10.1186/1476-9255-9-48 · Cited by 171
“Obesity is associated with a low-grade systemic chronic inflammation that is linked to insulin resistance, cardiovascular diseases and type-2 diabetes [1-3].”
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Palmitate-Induced Interleukin-6 Expression in Human Coronary Artery Endothelial Cells
Staiger, H., Staiger, K., Stefan, N., Wahl, H. G., Machicao, F. E., Kellerer, M., & Häring, H. (2004) · Diabetes · doi:10.2337/diabetes.53.12.3209 · Cited by 171
Atherosclerosis—An immune disease
Hansson, G. K. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.08.039 · Cited by 169
Retinol-Binding Protein 4 Is Associated with Insulin Resistance and Body Fat Distribution in Nonobese Subjects without Type 2 Diabetes
Gavi, S., Stuart, L. M., Kelly, P., Meléndez, M. M., Mynarcik, D. C., Gelato, M. C., & McNurlan, M. A. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1815 · Cited by 169
Renin‐Angiotensin‐Aldosterone System in Diabetes and Hypertension
Hsueh, W. A., & Wyne, K. L. (2011) · Journal of Clinical Hypertension · doi:10.1111/j.1751-7176.2011.00449.x · Cited by 166
Self-citation
Local adipose tissue depots as cardiovascular risk factors
Thalmann, S., & MEIER, C. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.03.008 · Cited by 166
“which are implicated in the regulation of food intake, inflammation and angiogenesis, either through systemic or local paracrine effects, ultimately resulting in a chronic low grade inflammatory state [10,11].”
Background
Adipokines and insulin resistance during pregnancy
Zavalza-Gómez, A. B., Anaya‐Prado, R., Rincón‐Sánchez, A. R., & Mora-Martínez, J. M. (2008) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2007.12.012 · Cited by 160
Paracrine role for periadventitial adipose tissue in the regulation of arterial tone
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Vascular endothelium dysfunction: a conservative target in metabolic disorders
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Cathepsin S, a novel biomarker of adiposity: relevance to atherogenesis
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“Some biomolecules related to inflammation process could directly or indirectly enhance atherogenesis in disorders like diabetes and the metabolic syndrome (3, 5, 6).”
Background
Resistance Training Reduces Subclinical Inflammation in Obese, Postmenopausal Women
Phillips, M. D., Patrizi, R. M., Cheek, D. J., Wooten, J. S., Barbee, J. J., & Mitchell, J. B. (2012) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3182644984 · Cited by 160
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“Besides its insulin-sensitizing effect, adionectin has also protective effects against atherosclerosis [121] and inflammation [122].”
Background
The Cannabinoid CB1 Receptor Antagonist Rimonabant (SR141716) Inhibits Cell Proliferation and Increases Markers of Adipocyte Maturation in Cultured Mouse 3T3 F442A Preadipocytes
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“…a crucial role in several pathophysiological processes, including obesity and associated diseases (Trayhurn and Beattie, 2001; Fortuno et al., 2003; Lyon et al., 2003; Rajala and Scherer, 2003; Reilly and Rader, 2003; Ruan and Lodish, 2003; Borst, 2004; Fain et al., 2004; Grundy, 2004; Matsuzawa…”
Influential
Early origins of inflammation: microbial exposures in infancy predict lower levels of C-reactive protein in adulthood
McDade, T. W., Rutherford, J., Adair, L., & Kuzawa, C. W. (2010) · Proceedings of the Royal Society B: Biological Sciences · doi:10.1098/rspb.2009.1795 · Cited by 162
“…this work has been conducted in relatively affluent settings with low levels of infectious disease, and it has focused on excess body fat—visceral adipose tissue in particular—as a primary source of pro-inflammatory cytokines that increase production of CRP (Lyon et al. 2003; Rexrode et al. 2003).”
Background
Inhibitory effect of naringenin chalcone on inflammatory changes in the interaction between adipocytes and macrophages
Hirai, S., Kim, Y.-I., Goto, T., Kang, M., Yoshimura, M., Obata, A., Yu, R., & Kawada, T. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.09.001 · Cited by 155
Obesity Increases Risk of Organ Failure after Severe Trauma
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Functional Adiponectin Resistance at the Level of the Skeletal Muscle in Mild to Moderate Chronic Heart Failure
Berendoncks, A. M. V., Garnier, A., Beckers, P. J., Hoymans, V. Y., Possemiers, N. M., Fortin, D., Martinet, W., Hoof, V. O. V., Vrints, C. J., Ventura‐Clapier, R., et al. (2010) · Circulation Heart Failure · doi:10.1161/circheartfailure.109.885525 · Cited by 154
Production and Release of Macrophage Migration Inhibitory Factor from Human Adipocytes
Skurk, T., Herder, C., Kräft, I., Müller-Scholze, S., Hauner, H., & Kolb, H. (2004) · Endocrinology · doi:10.1210/en.2004-0924 · Cited by 153
ICAM-1 expression in adipose tissue: effects of diet-induced obesity in mice
Brake, D. K., Smith, E. O., Mersmann, H. J., Smith, C. W., & Robker, R. L. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00008.2006 · Cited by 147
“Furthermore, evidence is rapidly accumulating that the links between adiposity and heightened immune cell activity are responsible for at least some manifestations of the metabolic syndrome, particularly atherosclerosis (1, 29).”
Background
Omega-3 fatty acid supplementation improves vascular function and reduces inflammation in obese adolescents
Dangardt, F., Osika, W., Chen, Y., Nilsson, U. A., Gan, L., Gronowitz, E., Strandvik, B., & Friberg, P. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.06.046 · Cited by 149
Obesity, Visceral Fat, and NAFLD: Querying the Role of Adipokines in the Progression of Nonalcoholic Fatty Liver Disease
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“Increasing visceral obesity is thought to result in increased production of proinflammatory cytokines and adipokines [tumour necrosis factor alpha, interleukin 6, and C reactive protein] [26, 156–158] and decreased production of protective adipokines [adiponectin] [28, 153, 156].”
Background
Nonalcoholic Fatty Liver Disease as a Contributor to Hypercoagulation and Thrombophilia in the Metabolic Syndrome
Targher, G., Chonchol, M., Miele, L., Zoppini, G., Pichiri, I., & Muggeo, M. (2009) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0029-1222606 · Cited by 144
Mechanisms of Disease: adipocytokines and visceral adipose tissue—emerging role in intestinal and mesenteric diseases
Schäffler, A., Schölmerich, J., & Büchler, C. (2005) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep0090 · Cited by 145
“Moreover, it has become evident that adipose tissue connects energy metabolism with immune function and host defense”
Background
Overexpression of Adiponectin Targeted to Adipose Tissue in Transgenic Mice: Impaired Adipocyte Differentiation
Bauche, I. B., Ait-El-Mkadem, S., Pottier, A.-M., Sènou, M., Many, M., Rezsöhazy, R., Pénicaud, L., Maeda, N., Funahashi, T., & Brichard, S. M. (2007) · Endocrinology · doi:10.1210/en.2006-0838 · Cited by 144
“It plays a fundamental role in energy homeostasis and inflammation (1).”
Background
Obesity and Lowered Cognitive Performance in a Canadian First Nations Population
Salerno, J., Bruce, S. G., Lou, W. Y. W., Hanley, A. J., Greenwood, C. E., & Young, T. K. (2009) · Obesity · doi:10.1038/oby.2009.161 · Cited by 143
“The contribution of atherosclerosis to silent infarcts (31) and the role of inflammatory factors such as adipocytokines or adipokines produced by abdominal visceral fat to the progression of endothelial dysfunction to atherosclerosis (32) are the possibilities.”
Background
Clinical Significance of Inflammatory Markers in Polycystic Ovary Syndrome: Their Relationship to Insulin Resistance and Body Mass Index
Samy, N., Hashim, M., Sayed, M., & Said, M. (2009) · Disease Markers · doi:10.1155/2009/465203 · Cited by 141
Metformin: Effects on Micro and Macrovascular Complications in Type 2 Diabetes
Bailey, C. J. (2008) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-008-6092-0 · Cited by 138
Inflammatory Responses Underlying the Microvascular Dysfunction Associated with Obesity and Insulin Resistance
Singer, G., & Granger, N. D. (2007) · Microcirculation · doi:10.1080/10739680701283158 · Cited by 140

Authors: Lyon, C. J., Law, R. E., & Hsueh, W. A.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Hsueh, Willa A.
ORCID: Lyon, Christopher J.
Hsueh, Willa A.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2003-06-01
Volume: 144
Issue: 6
Pages: 2195-2200
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2003-0285
OpenAlex: W1981444005
Cited by: 761
References: 121
Citations by year: 2026: 6 · 2025: 4 · 2024: 7 · 2023: 11 · 2022: 15 · 2021: 12 · 2020: 16 · 2019: 42 · 2018: 23 · 2017: 31 · 2016: 20 · 2015: 39 · 2014: 31 · 2013: 31 · 2012: 37
FWCI: 9.73
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (1P01 HIG0030-01A1)
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 › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: adiposity, adipokines, atherosclerosis, vascular inflammation, visceral adipose tissue, obesity, insulin resistance, hypertension, endothelial dysfunction, vascular remodeling, bariatric surgery, physical activity, caloric restriction, anti-inflammatory agents, hypercholesterolemia
MeSH terms: Adipose Tissue, Animals, Arteriosclerosis, Humans, Obesity, Vasculitis

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