LECT2 promotes inflammation and insulin resistance in adipocytes via P38 pathways
Open accessAbstract
Leukocyte cell-derived chemotaxin 2 (LECT2) is a recently identified novel hepatokine that causes insulin resistance in skeletal muscle by activating c-Jun N-terminal kinase (JNK), thereby driving atherosclerotic inflammation. However, the role of LECT2 in inflammation and insulin resistance in adipocytes has not been investigated. In this study, we report that LECT2 treatment of differentiated 3T3-L1 cells stimulates P38 phosphorylation in a dose-dependent manner. LECT2 also enhanced inflammation markers such as IκB phosphorylation, nuclear factor kappa beta (NF-κB) phosphorylation and IL-6 expression. Moreover, LECT2 treatment impaired insulin signaling in differentiated 3T3-L1 cells, as evidenced by the decreased levels of insulin receptor substrate (IRS-1) and Akt phosphorylation and reduced insulin-stimulated glucose uptake. Furthermore, LECT2 augmented lipid accumulation during 3T3-L1 cell differentiation by activating SREBP1c-mediated signaling. All these effects were significantly abrogated by siRNA-mediated silencing of P38, CD209 expression or a JNK inhibitor. Our findings suggest that LECT2 stimulates inflammation and insulin resistance in adipocytes via activation of a CD209/P38-dependent pathway. Thus, these results suggest effective therapeutic targets for treating inflammation-mediated insulin resistance.
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LECT2 treatment impairs insulin signaling in differentiated 3T3-L1 cells by decreasing levels of insulin receptor and AKT phosphorylation, reducing insulin-stimulated glucose uptake.
“Moreover, LECT2 treatment impaired insulin signaling in differentiated 3T3-L1 cells by decreasing levels of the insulin receptor and AKT phosphorylation, reducing insulin-stimulated glucose uptake [250].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [250]
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- Authors
- Jung, T. W., Chung, Y. H., Kim, H.-C., Abd El-Aty, A. M., & Jeong, J. H.
- Affiliations
- Seoul National University Bundang Hospital (KR)
- Chung-Ang University (KR)
- Kangwon National University (KR)
- 4Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
- Venue
- Journal of Molecular Endocrinology
- Publisher
- Bioscientifica
- Published
- 2018-07
- Volume
- 61
- Issue
- 1
- Pages
- 37-45
- ISSN
- 0952-5041 (ISSN-L)
- 1479-6813
- OpenAlex
- W2796814186
- Cited by
- 53
- References
- 36
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 10 · 2023: 8 · 2022: 10 · 2021: 10 · 2020: 4 · 2019: 4
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- Ministry of Science, ICT and Future Planning (2016R1C1B2012674)
- 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
- LECT2, hepatokines, insulin resistance, adipocytes, adipose tissue inflammation, p38 MAPK, DC-SIGN, JNK, NF-κB, IκB phosphorylation, interleukin-6, IRS-1, Akt signaling, insulin-stimulated glucose uptake, lipid accumulation, SREBP-1c, 3T3-L1 adipocytes
- MeSH terms
- Adipose Tissue, Animals, Inflammation, Insulin, Insulin Resistance, Adipocytes, MAP Kinase Signaling System, Intercellular Signaling Peptides and Proteins, 3T3-L1 Cells, Mice
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 ›
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