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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“Additionally, gEVs could contribute to WAT dysfunction by their impact on other cells in vivo, such as immune cells, considering their interactions in the development of adipose tissue dysfunction (Suganami et al. 2005; Nishimura et al. 2009).”
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Self-citation
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“The coculture of 3T3-L1 preadipocytes and BMDMs in an indirect coculture transwell system (#3450, CORNING, Corning, NY, USA) was performed as described previously (Suganami et al, 2005) with slight modi ﬁ cations.”
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Anti-inflammatory effect of Angiotensin 1-7 in white adipose tissue
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Types of cell culture inserts affect cell crosstalk between co-cultured macrophages and adipocytes
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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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