Cited by 1,056Adipokines, Inflammation, and Metabolic DiseasesCardiovascular Disease and AdiposityAdipose Tissue and Metabolism

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A Paracrine Loop Between Adipocytes and Macrophages Aggravates Inflammatory Changes: Role of Free Fatty Acids and Tumor Necrosis Factor α

Suganami, Takayoshi, Nishida, Junko, Ogawa, Yoshihiro·2005·Arteriosclerosis, Thrombosis, and Vascular Biology

DOI 10.1161/01.atv.0000183883.72263.13

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Abstract

Objective— Weight gain is associated with infiltration of fat by macrophages, suggesting that they are an important source of inflammation in obese adipose tissue. Here we developed an in vitro coculture system composed of adipocytes and macrophages and examined the molecular mechanism whereby these cells communicate. Methods and Results— Coculture of differentiated 3T3-L1 adipocytes and macrophage cell line RAW264 results in the marked upregulation of proinflammatory cytokines, such as tumor necrosis factor α (TNF-α), and the downregulation of the antiinflammatory cytokine adiponectin. Such inflammatory changes are induced by the coculture without direct contact, suggesting the role of soluble factors. A neutralizing antibody to TNF-α, which occurs mostly in macrophages, inhibits the inflammatory changes in 3T3-L1, suggesting that TNF-α is a major macrophage-derived mediator of inflammation in adipocytes. Conversely, free fatty acids (FFAs) may be important adipocyte-derived mediators of inflammation in macrophages, because the production of TNF-α in RAW264 is markedly increased by palmitate, a major FFA released from 3T3-L1. The inflammatory changes in the coculture are augmented by use of either hypertrophied 3T3-L1 or adipose stromal vascular fraction obtained from obese ob/ob mice. Conclusions— We postulate that a paracrine loop involving FFAs and TNF-α between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue.

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“The coculture of differentiated macrophages with mature adipocytes was adapted from previous studies using membrane inserts and demonstrating the cross-talk between two cell types (Harms et al., 2019; Suganami et al., 2005).”
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“7 macrophage의 coculture 시 TNF-α, MCP-1, NO와 같은 염증 매개체의 분비가 증가한 다는 보고[31]들에 의해 비만에 의한 염증반응이 대사성 질환 의 주요한 원인으로 작용한다는 것이 확인되었다.”
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Leukotriene C4 synthase is a novel PPARγ target gene, and leukotriene C4 and D4 activate adipogenesis through cysteinyl LT1 receptors in adipocytes
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“…levels of tumor necrosis factor-α (tNFα), which, in turn, stimulates adipocytes to produce more non-esterified fatty acids, pro-inflammatory cytokines such as interleukin-1β (il-1β) and il-6, acute phase proteins, and chemokines that attract more monocytes/macrophages into the adipose tissue [69].”
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Osteoblast versus Adipocyte: Bone Marrow Microenvironment-Guided Epigenetic Control
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Rosiglitazone‐dependent dissociation of HuR from PPAR‐γ regulates adiponectin expression at the posttranscriptional level
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Beneficial effect of ER stress preconditioning in protection against FFA-induced adipocyte inflammation via XBP1 in 3T3-L1 adipocytes
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Genetic and Structure-Function Studies of Missense Mutations in Human Endothelial Lipase
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Advanced Oxidation Protein Products Contribute to Chronic-Kidney-Disease-Induced Adipose Inflammation through Macrophage Activation
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“also reported that TNF-α is a major macrophag -derived paracrin mediator involved in adipose tissue inflammation [27].”
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“…with a continuous cycle of cross-talk between adipocytes and monocytes that contributes to further aggravate and perpetuate this pro-inflammatory status (41, 42). not all obese individuals exhibit increased risk of inflammation and not all normal-weight adults are metabolically healthy (36).”
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“DB extract decreased the expression of proinflammatory cytokines (TNF-a, MCP-1, and IL-6) in epididymal adipose tissue.”
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Macrophages Inhibit Insulin Signalling in Adipocytes: Role of Inducible Nitric Oxide Synthase and Nitric Oxide
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“collectively termed adipocytokines(31); adipose tissue inflammation reportedly contributes to the development of many aspects of metabolic syndrome, leading to diabetes and arteriosclerosis.(13,14,32) Of note, it has been reported that the expression levels of IL-6, TNF-α, IL-1β, and VEGF are associated with the progr…”
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Metabolic flux in macrophages in obesity and type-2 diabetes
Wong, A., Sun, Q., Latif, I. I., & Karwi, Q. G. (2024) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.3389/jpps.2024.13210 · Cited by 17
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“VAT secretes various adipokines leading to endothelial dysfunction(16-18).”
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Lipid Peroxidation in Obesity: Can Bariatric Surgery Help?
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Spleen IL-10, a key player in obesity-driven renal risk
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Aggressive Crosstalk Between Fatty Acids and Inflammation in Macrophages and Their Influence on Metabolic Homeostasis
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Regucalcin enhances adipocyte differentiation and attenuates inflammation in 3T3‐L1 cells
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Authors: Suganami, T., Nishida, J., & Ogawa, Y.
Affiliations: Tokyo Medical and Dental University (JP)
ORCID: Suganami, Takayoshi
Ogawa, Yoshihiro
Venue: Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2005-10
Volume: 25
Issue: 10
Pages: 2062-2068
ISSN: 1079-5642 (ISSN-L)
1524-4636
DOI: 10.1161/01.atv.0000183883.72263.13
OpenAlex: W2105448220
Cited by: 1,056
References: 45
Citations by year: 2026: 25 · 2025: 27 · 2024: 27 · 2023: 36 · 2022: 38 · 2021: 57 · 2020: 51 · 2019: 47 · 2018: 34 · 2017: 66 · 2016: 62 · 2015: 66 · 2014: 57 · 2013: 91 · 2012: 54
FWCI: 30.26
Type: journal article
Language: en
Open access: closed
Locations: Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
PubMed (publishedVersion)
Funders: Japan Research Foundation for Clinical Pharmacology
Ministry of Education, Culture, Sports, Science and Technology
Novo Nordisk
Smoking Research Foundation
Kanae Foundation for the Promotion of Medical Science
Mishima Kaiun Memorial Foundation
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: adipocytes, macrophages, paracrine signaling, adipose tissue inflammation, obesity, TNF-α, adiponectin, free fatty acids, palmitate, 3T3-L1 adipocytes, RAW264 macrophages, co-culture, ob/ob mice, adipose stromal vascular fraction, adipocyte hypertrophy
MeSH terms: Adipose Tissue, Animals, Cell Communication, Fatty Acids, Nonesterified, Gene Expression Regulation, Hypertrophy, Inflammation, Macrophages, Obesity, Tumor Necrosis Factor-alpha, Adipocytes, Coculture Techniques, Chemokine CCL2, Paracrine Communication, Metabolic Syndrome, 3T3-L1 Cells, Atherosclerosis, Mice

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A Paracrine Loop Between Adipocytes and Macrophages Aggravates Inflammatory Changes: Role of Free Fatty Acids and Tumor Necrosis Factor α

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