Format

Send to

Choose Destination
J Mol Endocrinol. 2018 Jul;61(1):37-45. doi: 10.1530/JME-17-0267. Epub 2018 Apr 12.

LECT2 promotes inflammation and insulin resistance in adipocytes via P38 pathways.

Author information

1
Research Administration Team, Seoul National University Bundang Hospital, Gyeonggi, Republic of Korea.
2
Department of Anatomy, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
3
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea.
4
Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
5
Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum, Turkey.
6
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.

Abstract

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.

KEYWORDS:

LECT2; NF-κB; P38; adipocyte; inflammation; insulin resistance

PMID:
29650721
DOI:
10.1530/JME-17-0267

Supplemental Content

Full text links

Icon for Sheridan PubFactory
Loading ...
Support Center