Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-α

Ruan, Hong; Lodish, Harvey F

doi:10.1016/s1359-6101(03)00052-2

Cited by 541Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-α

Ruan, Hong, Lodish, Harvey F·2003·Cytokine & Growth Factor Reviews

DOI 10.1016/s1359-6101(03)00052-2

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Abstract

Insulin resistance is a fundamental defect that precedes the development of the full insulin resistance syndrome as well as beta cell failure and type 2 diabetes. Tumor necrosis factor-alpha (TNF-alpha), a paracrine/autocrine factor highly expressed in adipose tissues of obese animals and human subjects, is implicated in the induction of insulin resistance seen in obesity and type 2 diabetes. Here, we review several molecular aspects of adipose tissue physiology, and highlight the direct effects of TNF-alpha on the functions of adipose tissue including induction of lipolysis, inhibition of insulin signaling, and alterations in expression of adipocyte important genes through activation of NF-kappaB, as well as their pertinence to insulin sensitivity of adipocytes. We also review the ability of TNF-alpha to inhibit synthesis of several adipocyte-specific proteins including Acrp30 (adiponectin) and enhance release of free fatty acids (FFAs) from adipose tissue, and discuss how these factors may act as systemic mediators of TNF-alpha and affect whole body energy homeostasis and overall insulin sensitivity. On the basis of these mechanisms, we examine the therapeutic potential of blocking specific autocrine/paracrine signaling pathways in adipocytes, particularly those involving NF-kappaB, in the treatment of type 2 diabetes.

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Authors: Ruan, H., & Lodish, H. F.
Affiliations: Whitehead Institute for Biomedical Research (US)
Corresponding author: Lodish, Harvey F
ORCID: Lodish, Harvey F
Venue: Cytokine & Growth Factor Reviews
Publisher: Elsevier BV
Published: 2003-10
Volume: 14
Issue: 5
Pages: 447-455
ISSN: 1359-6101 (ISSN-L)
DOI: 10.1016/s1359-6101(03)00052-2
OpenAlex: W2055844905
Cited by: 541
References: 122
Citations by year: 2026: 7 · 2025: 15 · 2024: 11 · 2023: 14 · 2022: 11 · 2021: 20 · 2020: 11 · 2019: 19 · 2018: 16 · 2017: 23 · 2016: 18 · 2015: 20 · 2014: 28 · 2013: 26 · 2012: 36
FWCI: 4.59
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cytokine & Growth Factor Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
American Diabetes Association
National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (R37DK047618)
Topics: Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: insulin resistance, adipose tissue, TNF-α, type 2 diabetes, obesity, lipolysis, insulin signaling, NF-κB, adiponectin, free fatty acids, energy homeostasis, adipocyte gene expression, autocrine and paracrine signaling, anti-inflammatory therapy
MeSH terms: Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Energy Metabolism, Fatty Acids, Nonesterified, Humans, Insulin, Insulin Resistance, Proteins, Tumor Necrosis Factor-alpha, Intercellular Signaling Peptides and Proteins, Adiponectin

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Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-α

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