Cited by 95Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismLipid metabolism and disorders

The role of lipolysis in mediating the proinflammatory effects of very low density lipoproteins in mouse peritoneal macrophages

Open access
Saraswathi, Viswanathan, Hasty, Alyssa H.·2006·Journal of Lipid Research

Abstract

Hypertriglyceridemia is an important risk factor for atherosclerosis, especially in obesity. Macrophages are one of the primary cell types involved in atherogenesis and are thought to contribute to lesion formation through both lipid accumulation and proinflammatory gene expression. In this study, we sought to determine the direct impact of triglyceride (TG)-rich VLDL-induced lipid accumulation on macrophage proinflammatory processes. Incubation of mouse peritoneal macrophages with 100 microg/ml VLDL for 6 h led to 2.8- and 3.7-fold increases in intracellular TGs and FFAs, respectively (P < 0.05). The inflammatory proteins tumor necrosis factor-alpha, interleukin-1beta, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, matrix metalloproteinase 3 (MMP3), and macrophage inflammatory protein-1alpha (MIP-1alpha) were all upregulated by at least 2-fold (P < 0.05) in a dose-dependent manner in VLDL-treated macrophages. The increase in inflammatory gene expression coincided with the phosphorylation of the mitogen-activated protein kinase (MAPK) pathway members extracellular signal-regulated kinase (ERK) 1/2, stress-activated protein kinase/c-Jun NH2-terminal kinase, and p38 MAPK and was ameliorated by U0126, an inhibitor of ERK1/2. Inhibition of extracellular TG hydrolysis with tetrahydrolipstatin (Orlistat) resulted in the absence of intracellular TG and FFA accumulation and was accompanied by the amelioration of ERK1/2 phosphorylation and MIP-1alpha gene expression. These data indicate that VLDL hydrolysis, and the subsequent accumulation of intracellular FFAs and TGs, plays a substantive role in mediating the proinflammatory effects of VLDL. These data have important implications for the direct proatherogenic effects of VLDL on macrophage-driven atherosclerosis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1194/jlr.m600159-jlr200

Cites

50 of 50 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The hydrolysis of remnant TGs by lipoprotein lipase at the endothelial surface or within the subendothelial space generates a host of proinflammatory mediators.

    “the hydrolysis of remnant TGs by lipoprotein lipase at the endothelial surface or within the subendothelial space generates a host of proinflammatory mediators (25).”

    From Triglycerides and residual atherosclerotic risk (2021) · cites this paper as [25]

  • Direct incubation of mouse peritoneal macrophages with TRL increases macrophage cell triglyceride and fatty acid content and increases expression of macrophage inflammatory proteins.

    “For example, direct incubation of mouse peritoneal macrophages with TRL increases macrophage cell triglyceride and fatty acid content; more importantly, this incubation increases expression of macrophage inflammatory proteins, including tumor necrosis factor-␣, interleukin-1␤, monocyte chemotactic protein-1, intercellular adhesion molecule-1, and matrix metalloproteinase-3. 83,84”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Saraswathi, V., & Hasty, A. H.
Affiliations
  • Vanderbilt University Medical Center (US)
  • Vanderbilt University (US)
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2006-07
Volume
47
Issue
7
Pages
1406-1415
ISSN
0022-2275 (ISSN-L)
OpenAlex
W2141939352
Cited by
95
References
50
Citations by year
2026: 1 · 2025: 3 · 2023: 3 · 2022: 8 · 2021: 4 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 6 · 2014: 5 · 2013: 9 · 2012: 8
FWCI
2.02
Type
journal article
Language
en
Open access
Locations
  • Journal of Lipid Research (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American Diabetes Association (1-04-JF-20)
  • American Heart Association (0330011N)
  • Vanderbilt University
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-26657, DK59637, DK 20593, P30DK026657)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
VLDL, lipolysis, triglyceride-rich lipoproteins, peritoneal macrophages, macrophage inflammation, atherosclerosis, hypertriglyceridemia, free fatty acids, TNF-α, IL-1β, MCP-1, ICAM-1, matrix metalloproteinase-3, macrophage inflammatory protein-1alpha, ERK1/2 phosphorylation, MAPK signaling, orlistat, proatherogenic effects
MeSH terms
Animals, Esterification, Female, Humans, Hydrolysis, Lipolysis, Lipoproteins, VLDL, Mice, Inbred C57BL, Phosphorylation, Triglycerides, Gene Expression, Macrophages, Peritoneal, Inflammation Mediators, Macrophage Inflammatory Proteins, MAP Kinase Signaling System, Lipid Metabolism, Mice, Chemokine CCL3, Chemokine CCL4, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review