Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Aug;56(8):1212-22.
doi: 10.1002/mnfr.201200058. Epub 2012 Jun 15.

Dietary saturated fatty acids prime the NLRP3 inflammasome via TLR4 in dendritic cells-implications for diet-induced insulin resistance

Clare M Reynolds  1 , Fiona C McGillicuddy, Karen A Harford, Orla M Finucane, Kingston H G Mills, Helen M Roche
Affiliations

Dietary saturated fatty acids prime the NLRP3 inflammasome via TLR4 in dendritic cells-implications for diet-induced insulin resistance

Clare M Reynolds et al. Mol Nutr Food Res. 2012 Aug.

Abstract

Scope: Inflammasome-mediated inflammation is a critical regulator of obesity-induced insulin resistance (IR). We hypothesized that saturated fatty acids (SFA) directly prime the NLRP3 inflammasome via TLR4 concurrent with IR. We focused on dendritic cells (DCs) (CD11c(+) CD11b(+) F4/80(-) ), which are recruited into obese adipose tissue following high-fat diet (HFD) challenge and are a key cell in inflammasome biology.

Methods and results: C57BL/6 mice were fed HFD for 16 weeks (45% kcal palm oil), glucose homeostasis was monitored by glucose and insulin tolerance tests. Stromal vascular fraction (SVF) cells were isolated from adipose and analyzed for CD11c(+) CD11b(+) F480(-) DC. Following coculture with bone marrow derived DC (BMDC) insulin-stimulated (3) H-glucose transport into adipocytes, IL-1β secretion and caspase-1 activation was monitored. BMDCs primed with LPS (100 ng/mL), linoleic acid (LA; 200 μM), or palmitic acid (PA; 200 μM) were used to monitor inflammasome activation. We demonstrated significant infiltration of DCs into adipose after HFD. HFD-derived DCs reduce adipocyte insulin sensitivity upon coculture co-incident with enhanced adipocyte caspase-1 activation/IL-1β secretion. HFD-derived DCs are skewed toward a pro-inflammatory phenotype with increased IL-1β secretion, IL-1R1, TLR4, and caspase-1 expression. Complementary in vitro experiments demonstrate that TLR4 is critical in propagating SFA-mediated inflammasome activation.

Conclusion: SFA represent metabolic triggers priming the inflammasome, promoting adipocyte inflammation/IR, suggesting direct effects of SFA on inflammasome activation via TLR4.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources