Short Term High Fat Diet Challenge Promotes Alternative Macrophage Polarization in Adipose Tissue via Natural Killer T Cells and Interleukin-4
Open accessAbstract
Inflammation in adipose tissue plays an important role in the pathogenesis of obesity-associated complications. However, the detailed cellular events underlying the inflammatory changes at the onset of obesity have not been characterized. Here we show that an acute HFD challenge is unexpectedly associated with elevated alternative (M2) macrophage polarization in adipose tissue mediated by Natural Killer T (NKT) cells. Upon 4d HFD feeding, NKT cells are activated, promote M2 macrophage polarization and induce arginase 1 expression via interleukin (IL)-4 in adipose tissue, not in the liver. In NKT-deficient CD1d −/− mice, M2 macrophage polarization in adipose tissue is reduced while systemic glucose homeostasis and insulin tolerance are impaired upon 4d HFD challenge. Thus, our study demonstrate, for the first time to our knowledge, that acute HFD feeding is associated with remarkably pronounced and dynamic immune responses in adipose tissue, and adipose-resident NKT cells may link acute HFD feeding with inflammation. Background: Our understanding of immune responses at early stages of obesity is very limited. Results: Acute HFD feeding promotes alternative macrophage polarization in adipose tissue via NKT cells and IL-4. Conclusion: NKT cells in adipose tissue play important role in linking acute HFD feeding with adipose inflammation. Significance: Acute HFD feeding is unexpectedly associated with pronounced and dynamic immune responses in adipose tissue.
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NKT cell actions are likely beneficial for adaptation of adipose tissue to acute high-fat feeding because CD1d-deficient mice do not activate adipose NKT cells and display exacerbated insulin resistance.
“The actions of NKT cells are likely beneficial for the adaptation of AT to acute HFF because mice deficient in CD1d do not activate AT NKT cells and display exacerbated insulin resistance (17).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [17]
Acute high-fat feeding induces antiinflammatory immune cell actions, cell repair signaling, and angiogenesis.
“that acute HFF induces antiinflammatory immune cell actions, cell repair signaling, and angiogenesis (1,17,18).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [17]
Acute high-fat-diet stress leads to activation of antiinflammatory macrophages in some reports.
“In contrast, others have reported that acute HFD stress leads to activation of antiinflammatory macrophages (17,18).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [17]
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- Authors
- Ji, Y., Sun, S., Xia, S., Yang, L., Li, X., & Qi, L.
- Affiliations
- Cornell University (US)
- Corresponding author
- Qi, Ling
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 287
- Issue
- 29
- Pages
- 24378-24386
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3397864
- OpenAlex
- W2023869169
- Cited by
- 150
- References
- 51
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 10 · 2022: 4 · 2021: 8 · 2020: 9 · 2019: 15 · 2018: 10 · 2017: 12 · 2016: 9 · 2015: 14 · 2014: 21 · 2013: 19 · 2012: 4
- FWCI
- 13.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK082582, R01-DK-082582-S1)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- high-fat diet, adipose tissue inflammation, M2 macrophage polarization, NKT cells, IL-4, arginase-1, obesity, CD1d, glucose homeostasis, insulin tolerance
- MeSH terms
- Adipose Tissue, Animals, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Macrophages, Blotting, Western, Interleukin-4, Stromal Cells, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Mice, Adipose Tissue, White, Natural Killer T-Cells, Diet, High-Fat
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