Cited by 2,212Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

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Inflammatory mechanisms linking obesity and metabolic disease

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Saltiel, Alan R., Olefsky, Jerrold M.·2017·Journal of Clinical Investigation

DOI 10.1172/jci92035PMC PMC5199709

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Abstract

There are currently over 1.9 billion people who are obese or overweight, leading to a rise in related health complications, including insulin resistance, type 2 diabetes, cardiovascular disease, liver disease, cancer, and neurodegeneration. The finding that obesity and metabolic disorder are accompanied by chronic low-grade inflammation has fundamentally changed our view of the underlying causes and progression of obesity and metabolic syndrome. We now know that an inflammatory program is activated early in adipose expansion and during chronic obesity, permanently skewing the immune system to a proinflammatory phenotype, and we are beginning to delineate the reciprocal influence of obesity and inflammation. Reviews in this series examine the activation of the innate and adaptive immune system in obesity; inflammation within diabetic islets, brain, liver, gut, and muscle; the role of inflammation in fibrosis and angiogenesis; the factors that contribute to the initiation of inflammation; and therapeutic approaches to modulate inflammation in the context of obesity and metabolic syndrome.

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Result
Enhanced Adipose Expression of Interferon Regulatory Factor (IRF)-5 Associates with the Signatures of Metabolic Inflammation in Diabetic Obese Patients
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“Increasing evidence supports that metabolic inflammation is a consequence of obesity and it may play, in turn, a causative role in blunting insulin sensitivity and disrupting metabolic/energy homeostasis [1,2].”
Background
Homeostatic Regulation of Glucose Metabolism by the Central Nervous System
Choi, J. H., & Kim, M.-S. (2022) · Endocrinology and Metabolism · doi:10.3803/enm.2021.1364 · Cited by 52
“Similar pathological events may also occur in the brain areas that control glucose metabolism [95].”
Background
Catechins and Proanthocyanidins Involvement in Metabolic Syndrome
Patanè, G. T., Putaggio, S., Tellone, E., Barreca, D., Ficarra, S., Maffei, C., Calderaro, A., & Laganà, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119228 · Cited by 45
Natural products targeting inflammation-related metabolic disorders: A comprehensive review
Nainu, F., Frediansyah, A., Mamada, S. S., Permana, A. D., Salampe, M., Chandran, D., Emran, T. B., & Simal‐Gándara, J. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e16919 · Cited by 48
“Nevertheless, chronic inflammation appears to be one of the key players in the initiation, progression, and transition of the abovementioned metabolic disorders [103,129,225,269].”
BackgroundInfluential
Complete Blood Count (CBC)-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Adults with Severe Obesity
Marra, A., Bondesan, A., Caroli, D., & Sartório, A. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13051353 · Cited by 47
“During an inflammatory response, the body activates a series of events involving circulating white blood cells (i.e., neutrophils) [14], which in turn may stimulate the secretion of cytokines and proteolytic enzymes.”
Background
Microglia immunometabolism: From metabolic disorders to single cell metabolism
Paolicelli, R. C., & Angiari, S. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.03.012 · Cited by 47
Sacha inchi oil alleviates gut microbiota dysbiosis and improves hepatic lipid dysmetabolism in high-fat diet-fed rats
Li, P., Huang, J., Xiao, N., Cai, X., Yang, Y., Deng, J., Zhang, L., & Du, B. (2020) · Food & Function · doi:10.1039/d0fo01178a · Cited by 49
Effect of soybean milk fermented with Lactobacillus plantarum HFY01 isolated from yak yogurt on weight loss and lipid reduction in mice with obesity induced by a high-fat diet
Li, C., Liu, H., Yang, J., Mu, J., Wang, R., & Zhao, X. (2020) · RSC Advances · doi:10.1039/d0ra06977a · Cited by 45
Domeless receptor loss in fat body tissue reverts insulin resistance induced by a high-sugar diet in Drosophila melanogaster
Lourido, F., Quenti, D., Salgado-Canales, D., & Tobar, N. (2021) · Scientific Reports · doi:10.1038/s41598-021-82944-4 · Cited by 48
From Metabolic Syndrome to Neurological Diseases: Role of Autophagy
Maiuolo, J., Gliozzi, M., Musolino, V., Carresi, C., Scarano, F., Nucera, S., Scicchitano, M., Bosco, F., Ruga, S., Zito, M. C., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.651021 · Cited by 49
The intestinal mycobiome as a determinant of host immune and metabolic health
Gutierrez, M. W., & Arrieta, M. (2021) · Current Opinion in Microbiology · doi:10.1016/j.mib.2021.04.004 · Cited by 45
Effects of High-fat Diet and Chronic Mild Stress on Depression-like Behaviors and Levels of Inflammatory Cytokines in the Hippocampus and Prefrontal Cortex of Rats
Wang, W., Yang, J., Xu, J., Yu, H., Liu, Y., Wang, R., Ho, R., Ho, C. S. H., & Pan, F. (2021) · Neuroscience · doi:10.1016/j.neuroscience.2021.11.015 · Cited by 46
Folic Acid Attenuates High-Fat Diet-Induced Osteoporosis Through the AMPK Signaling Pathway
He, H., Zhang, Y., Sun, Y., Zhang, Y., Xu, J., Yang, Y., & Chen, J. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.791880 · Cited by 44
Type 2 Diabetes and Alzheimer’s Disease: The Emerging Role of Cellular Lipotoxicity
Marrano, N., Biondi, G., Borrelli, A., Rella, M., Zambetta, T., Gioia, L. D., Caporusso, M., Logroscino, G., Perrini, S., Giorgino, F., et al. (2023) · Biomolecules · doi:10.3390/biom13010183 · Cited by 44
Obesity, obesities and gastrointestinal cancers
Zou, Y., & Pitchumoni, C. S. (2023) · Disease-a-Month · doi:10.1016/j.disamonth.2023.101592 · Cited by 47
Identifying Microbe-Disease Association Based on a Novel Back-Propagation Neural Network Model
Li, H., Wang, Y., Zhang, Z., Tan, Y., Chen, Z., Wang, X., Pei, T., & Wang, L. (2020) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2020.2986459 · Cited by 44
“Obesity is more likely to cause health complications such as insulin resistance, type 2 diabetes, cardiovascular disease, liver disease, cancer, and neurodegeneration [68].”
Background
Swertiamarin supplementation prevents obesity-related chronic inflammation and insulin resistance in mice fed a high-fat diet
Xu, L., Li, D., Zhu, Y., Cai, S., Liang, X., Ying, T., Jin, S., & Ding, C. (2021) · Adipocyte · doi:10.1080/21623945.2021.1906510 · Cited by 43
“tance, has been observed in association with a higher fat mass [3,4].”
Background
Non-linear associations of atherogenic index of plasma with prediabetes and type 2 diabetes mellitus among Chinese adults aged 45 years and above: a cross-sectional study from CHARLS
Jiang, L., Li, L., Xu, Z., Tang, Y. R., Zhai, Y., Fu, X., Liu, D., & Wu, Q. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1360874 · Cited by 43
Cardiotonic Steroids and the Sodium Trade Balance: New Insights into Trade-Off Mechanisms Mediated by the Na+/K+-ATPase
Khalaf, F. K., Dube, P. R., Mohamed, A., Tian, J., Malhotra, D. K., Haller, S. T., & Kennedy, D. J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092576 · Cited by 43
“Diabetes mellitus is another inflammation-related process that appears to be increasing rapidly, threatening to reduce life expectancy for humans worldwide [99,105].”
Background
Polyunsaturated fatty acids, specialized pro-resolving mediators, and targeting inflammation resolution in the age of precision nutrition
Al‐Shaer, A. E., Buddenbaum, N., & Shaikh, S. R. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2021.158936 · Cited by 47
Integrating Omics Technologies for a Comprehensive Understanding of the Microbiome and Its Impact on Cattle Production
Kaur, H., Kaur, G., Gupta, T., Mittal, D., & Ali, S. A. (2023) · Biology · doi:10.3390/biology12091200 · Cited by 47
“A more comprehensive investigation is warranted to thoroughly grasp the contributions of the lower-gut microbiome to both animal health and productive outcomes [110].”
Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus
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Ginkgetin, a biflavone from Ginkgo biloba leaves, prevents adipogenesis through STAT5-mediated PPARγ and C/EBPα regulation
Cho, Y., Park, J., Kang, H. J., Kim, W., Cho, M. J., Jang, J.-H., Kwon, M., Kim, S., Lee, S., Lee, J., et al. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.11.027 · Cited by 42
Anthocyanin supplementation inhibits secretion of pro-inflammatory cytokines in overweight and obese individuals
Vugic, L., Colson, N., Nikbakht, E., Gaiz, A. A., Holland, O. J., Kundur, A., & Singh, I. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.103596 · Cited by 47
“…found cytokines such as interleukin (IL)-6, IL-1β and chemokine (C-C motif) ligand 2 (CCL2; also known as monocyte chemoattractant protein-1 (MCP-1)) were elevated in the adipose tissue of obese animals and humans (Bing, 2015; Eder, Baffy, Falus, & Fulop, 2009; Panee, 2012; Reilly & Saltiel, 2017).”
Background
Adipocyte Gi signaling is essential for maintaining whole-body glucose homeostasis and insulin sensitivity
Wang, L., Pydi, S. P., Zhu, L., Barella, L. F., Cui, Y., Gavrilova, O., Bence, K. K., Vernochet, C., & Wess, J. (2020) · Nature Communications · doi:10.1038/s41467-020-16756-x · Cited by 43
Berries as a Treatment for Obesity-Induced Inflammation: Evidence from Preclinical Models
Lail, H. L., Feresin, R. G., Hicks, D., Stone, B., Price, E., & Wanders, D. (2021) · Nutrients · doi:10.3390/nu13020334 · Cited by 46
“The heightened inflammatory state of these metabolically important tissues has been postulated to increase the risk of developing type 2 diabetes [6,7], cardiovascular disease [8], and cancer [9].”
Background
Phase angle as an easy diagnostic tool for the nutritionist in the evaluation of inflammatory changes during the active stage of a very low-calorie ketogenic diet
Barrea, L., Muscogiuri, G., Aprano, S., Vetrani, C., de Alteriis, G., Varcamonti, L., Verde, L., Colao, A., & Savastano, S. (2022) · International Journal of Obesity · doi:10.1038/s41366-022-01152-w · Cited by 46
“Chronic, low-grade inflammation associated with excess, dysfunctional visceral adipose tissue is an underlying feature of obesity-related diseases [35].”
Background
Obesity and COVID-19: A Fatal Alliance
Banerjee, M., Gupta, S., Sharma, P., Shekhawat, J. K., & Gauba, K. (2020) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-020-00909-2 · Cited by 41
Proteobacteria impair anti-tumor immunity in the omentum by consuming arginine
Meza‐Perez, S., Liu, M., Silva-Sánchez, A., Morrow, C. D., Eipers, P. G., Lefkowitz, E. J., Ptacek, T., Scharer, C. D., Rosenberg, A. F., Hill, D. D., et al. (2024) · Cell Host & Microbe · doi:10.1016/j.chom.2024.06.003 · Cited by 42
Brazilian propolis ethanol extract and its component kaempferol induce myeloid-derived suppressor cells from macrophages of mice in vivo and in vitro
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“Background Low-grade inflammation in adipose tissue is a hallmark of type 2 diabetes and adiposity [1].”
Stronger anti-obesity effect of white ginseng over red ginseng and the potential mechanisms involving chemically structural/compositional specificity to gut microbiota
Zhou, S.-S., Au-Yeung, K. K. W., Yip, K.-M., Ye, R., Zhao, Z., Mao, Q., Xu, J., Chen, H., & Li, S. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.11.021 · Cited by 42
Apolipoprotein M: a novel adipokine decreasing with obesity and upregulated by calorie restriction
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Daily Intake of Paraprobiotic Lactobacillus amylovorus CP1563 Improves Pre-Obese Conditions and Affects the Gut Microbial Community in Healthy Pre-Obese Subjects: A Double-Blind, Randomized, Placebo-Controlled Study
Sugawara, T., Sawada, D., Yanagihara, S., Aoki, Y., Takehara, I., Sugahara, H., Hirota, T., Nakamura, Y., & Ishikawa, S. (2020) · Microorganisms · doi:10.3390/microorganisms8020304 · Cited by 41
“Several studies have shown that the adipose tissue of obese organisms exhibits chronic low-grade inflammation [50,51], and upregulating anti-inflammatory immune activities by increasing the level of butyrate has the potential to affect obesity.”
Background
General and Central Obesity Are Associated With Increased Severity of the VMS and Sexual Symptoms of Menopause Among Chinese Women: A Longitudinal Study
Tang, R., Fan, Y., Luo, M., Zhang, D., Xie, Z., Huang, F., Wang, Y., Liu, G., Wang, Y., Lin, S., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.814872 · Cited by 40
“Overweight and obesity are established risk factors for many metabolic diseases (33), which have become an increasingly public health problem.”
Background
Nanocarrier-Assisted Delivery of Metformin Boosts Remodeling of Diabetic Periodontal Tissue via Cellular Exocytosis-Mediated Regulation of Endoplasmic Reticulum Homeostasis
Zhong, W., Wang, X., Yang, L., Wang, Y., Xiao, Q., Yu, S., Cannon, R. D., Bai, Y., Zhang, C., Chen, D., et al. (2022) · ACS Nano · doi:10.1021/acsnano.2c08146 · Cited by 40
Association between vitamin D status and metabolic syndrome risk factors
Barbalho, S. M., Tofano, R. J., de Campos, A. L., Rodrigues, A. S., Quesada, K. R., Bechara, M. D., Goulart, R. D. Á., & Oshiiwa, M. (2018) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2018.03.011 · Cited by 40

Authors: Saltiel, A. R., & Olefsky, J. M.
Affiliations: University of California San Diego (US)
ORCID: Saltiel, Alan R.
Olefsky, Jerrold M.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2017-01-03
Volume: 127
Issue: 1
Pages: 1-4
ISSN: 0021-9738 (ISSN-L)
1558-8238
DOI: 10.1172/jci92035
PMC: PMC5199709
OpenAlex: W2567264284
Cited by: 2,212
References: 44
Citations by year: 2026: 261 · 2025: 318 · 2024: 265 · 2023: 255 · 2022: 308 · 2021: 280 · 2020: 270 · 2019: 136 · 2018: 80 · 2017: 36
FWCI: 18.93
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: University of California, San Diego (P30DK063491, DK063491)
National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, P30DK063491)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords: obesity, metabolic syndrome, low-grade inflammation, insulin resistance, type 2 diabetes, adipose tissue expansion, innate immune system, adaptive immunity, neuroinflammation, liver inflammation, intestinal inflammation, skeletal muscle inflammation, fibrosis, angiogenesis, anti-inflammatory therapy
MeSH terms: Animals, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Humans, Inflammation, Neoplasms, Obesity, Organ Specificity, Neurodegenerative Diseases, Metabolic Syndrome

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