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Cited by 334Adipokines, Inflammation, and Metabolic DiseasesImmune Response and InflammationAdipose Tissue and Metabolism

Tlr-4 deficiency selectively protects against obesity induced by diets high in saturated fat

Davis, Jeremy E., Gabler, Nicholas K., Walker‐Daniels, Jennifer, Spurlock, Michael E.·2008·Obesity
DOI 10.1038/oby.2008.210
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Abstract

Toll‐like receptor‐4 (Tlr‐4), a key pattern recognition receptor involved in innate immune response, is activated by saturated fatty acids (SFAs). To investigate the involvement of this receptor in obesity caused by consumption of diets high in fat, we utilized male Tlr‐4‐deficient 10ScN mice and 10J controls. Mice were fed either low fat (low‐fat control (LFC)), high unsaturated fat (high‐fat control (HFC)), or high saturated fat + palmitate (HFP) diets ad libitum for 16 weeks. Relative to the LFC diet, the HFC diet resulted in greater epididymal fat pad weights and adipocyte hypertrophy in both Tlr‐4‐deficient and normal mice. However, the 10ScN mice were completely protected against the obesigenic effects of the HFP diet. Moreover, macrophage infiltration and monocyte chemotactic protein‐1 (MCP‐1) transcript abundance were lower in adipose tissue of 10ScN mice fed the HFP diet, and the hyperinsulinemic response was negated. Tlr‐4‐deficient mice also had markedly lower circulating concentrations of MCP‐1 and much less nuclear factor‐κB (NFκB) protein in nuclear extracts prepared from adipose tissue, irrespective of diet. In contrast, Tlr‐4 deficiency did not attenuate the induction of tumor necrosis factor‐α (TNF‐α) or interleukin‐6 (IL‐6) expression in adipose tissue. These data indicate that Tlr‐4 deficiency selectively protects against the obesigenic effects of SFA and alters obesity‐related inflammatory responses in adipose tissue.

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Crossref · 10.1038/oby.2008.210

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  • FFA activates NF-κB through TLR4, leading to the expression of monocyte chemotactic protein-1 to recruit macrophages, which further produce IL-6 and TNFα.

    “In line with these findings, FFA activates NF-κB through TLR4, leading to the expression of monocyte chemotactic protein-1 (MCP-1) to recruit macrophages, which further produce IL-6 and TNFα (307, 308).”

    From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [307]

  • In rodents, high saturated fat content causes hyperinsulinemia, liver and muscle insulin resistance, and hypothalamic inflammation.

    “which in rodents causes hyperinsulinemia, liver and muscle insulin resistance, and hypothalamic inflammation (137–143).”

    From The carbohydrate-insulin model: A physiological perspective on the obesity pandemic (2021) · cites this paper as [143]

  • Substitution of unsaturated fat for saturated fat in these protocols, or ablation of toll-like receptor signaling, reduces metabolic dysfunction and adiposity in rodents.

    “Substitution of unsaturated fat for saturated fat in these protocols, or ablation of toll-like receptor signaling, reduces metabolic dysfunction and adiposity (137–143).”

    From The carbohydrate-insulin model: A physiological perspective on the obesity pandemic (2021) · cites this paper as [143]

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Authors
Davis, J. E., Gabler, N. K., Walker‐Daniels, J., & Spurlock, M. E.
Affiliations
Iowa State University (US)
Corresponding author
Spurlock, Michael E.
ORCID
Venue
Obesity
Publisher
Wiley
Published
2008-06
Volume
16
Issue
6
Pages
1248-1255
ISSN
  • 1930-7381 (ISSN-L)
  • 1930-739X
DOI
10.1038/oby.2008.210
OpenAlex
W2069746141
Cited by
334
References
31
Citations by year
2026: 6 · 2025: 5 · 2024: 5 · 2023: 11 · 2022: 12 · 2021: 15 · 2020: 14 · 2019: 20 · 2018: 12 · 2017: 16 · 2016: 18 · 2015: 25 · 2014: 20 · 2013: 35 · 2012: 35
FWCI
21.03
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1558 d)
Locations
  • Obesity (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
TLR4, saturated fatty acids, high-fat diet, adipose tissue inflammation, macrophage infiltration, MCP-1, NF-κB, adipocyte hypertrophy, palmitate, innate immunity
MeSH terms
Adipose Tissue, Animals, Blood Glucose, Energy Intake, Dietary Fats, Fatty Acids, Insulin, Insulin Resistance, Macrophages, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Obesity, Random Allocation, Tumor Necrosis Factor-alpha, Interleukin-6, NF-kappa B, Mice, Knockout, Chemokine CCL2, Adiposity, Toll-Like Receptor 4, Mice

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