Tags

Type your tag names separated by a space and hit enter

METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice.
Exp Mol Med 2018; 50(9):122EM

Abstract

Physical activity has many beneficial effects on metabolic disorders, such as obesity, insulin resistance, and diabetes. Meteorin-like protein (METRNL), a novel secreted protein homologous to the neurotrophin Metrn, is induced after exercise in the skeletal muscle. Herein, we investigated the effects of METRNL on lipid-mediated inflammation and insulin resistance in skeletal muscle via AMP-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor δ (PPARδ). Treatment with METRNL suppressed inflammatory markers, such as nuclear factor κB (NFκB) nuclear translocation, inhibitory κBα (IκBα) phosphorylation, interleukin-6 (IL-6) expression, and pro-inflammatory cytokines (such as TNFα and MCP-1). METRNL treatment also attenuated the impaired insulin response both in palmitate-treated differentiated C2C12 cells and the skeletal muscle of high-fat diet (HFD)-fed mice. Furthermore, METRNL administration rescued glucose intolerance and reduced HFD-induced body weight gain in mice; however, METRNL did not affect calorie intake. METRNL treatment increased AMPK phosphorylation and PPARδ expression both in differentiated C2C12 cells and mouse skeletal muscle. siRNA-mediated suppression of AMPK and PPARδ abrogated the suppressive effects of METRNL on palmitate-induced inflammation and insulin resistance. Moreover, METRNL augmented the mRNA expression of fatty acid oxidation-associated genes, such as carnitine palmitoyltransferase 1 (CPT1), acyl-CoA oxidase (ACO), and fatty acid binding protein 3 (FABP3). siRNAs for AMPK and PPARδ reversed these changes. In the current study, we report for the first time that METRNL alleviates inflammation and insulin resistance and induces fatty acid oxidation through AMPK or PPARδ-dependent signaling in skeletal muscle.

Authors+Show Affiliations

Research Administration Team, Seoul National University Bundang Hospital, Seongnam, Korea.College of Pharmacy, Chung-Ang University, Seoul, Korea.Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Korea.College of Pharmacy, Sookmyung Women's University, Seoul, Korea.Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 12211, Giza, Egypt. Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum, Turkey.Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum, Turkey.Department of Pharmacology, College of Medicine, Chung-Ang University, 221, Heuksuk-dong, Dongjak-gu, Seoul, 156-756, Korea. syk@cau.ac.kr.Department of Pharmacology, College of Medicine, Chung-Ang University, 221, Heuksuk-dong, Dongjak-gu, Seoul, 156-756, Korea. jhjeong3@cau.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30213948

Citation

Jung, Tae Woo, et al. "METRNL Attenuates Lipid-induced Inflammation and Insulin Resistance Via AMPK or PPARδ-dependent Pathways in Skeletal Muscle of Mice." Experimental & Molecular Medicine, vol. 50, no. 9, 2018, p. 122.
Jung TW, Lee SH, Kim HC, et al. METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice. Exp Mol Med. 2018;50(9):122.
Jung, T. W., Lee, S. H., Kim, H. C., Bang, J. S., Abd El-Aty, A. M., Hacımüftüoğlu, A., ... Jeong, J. H. (2018). METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice. Experimental & Molecular Medicine, 50(9), p. 122. doi:10.1038/s12276-018-0147-5.
Jung TW, et al. METRNL Attenuates Lipid-induced Inflammation and Insulin Resistance Via AMPK or PPARδ-dependent Pathways in Skeletal Muscle of Mice. Exp Mol Med. 2018 09 13;50(9):122. PubMed PMID: 30213948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice. AU - Jung,Tae Woo, AU - Lee,Sung Hoon, AU - Kim,Hyoung-Chun, AU - Bang,Joon Seok, AU - Abd El-Aty,A M, AU - Hacımüftüoğlu,Ahmet, AU - Shin,Yong Kyoo, AU - Jeong,Ji Hoon, Y1 - 2018/09/13/ PY - 2018/04/13/received PY - 2018/07/25/accepted PY - 2018/07/03/revised PY - 2018/9/15/entrez PY - 2018/9/15/pubmed PY - 2019/5/18/medline SP - 122 EP - 122 JF - Experimental & molecular medicine JO - Exp. Mol. Med. VL - 50 IS - 9 N2 - Physical activity has many beneficial effects on metabolic disorders, such as obesity, insulin resistance, and diabetes. Meteorin-like protein (METRNL), a novel secreted protein homologous to the neurotrophin Metrn, is induced after exercise in the skeletal muscle. Herein, we investigated the effects of METRNL on lipid-mediated inflammation and insulin resistance in skeletal muscle via AMP-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor δ (PPARδ). Treatment with METRNL suppressed inflammatory markers, such as nuclear factor κB (NFκB) nuclear translocation, inhibitory κBα (IκBα) phosphorylation, interleukin-6 (IL-6) expression, and pro-inflammatory cytokines (such as TNFα and MCP-1). METRNL treatment also attenuated the impaired insulin response both in palmitate-treated differentiated C2C12 cells and the skeletal muscle of high-fat diet (HFD)-fed mice. Furthermore, METRNL administration rescued glucose intolerance and reduced HFD-induced body weight gain in mice; however, METRNL did not affect calorie intake. METRNL treatment increased AMPK phosphorylation and PPARδ expression both in differentiated C2C12 cells and mouse skeletal muscle. siRNA-mediated suppression of AMPK and PPARδ abrogated the suppressive effects of METRNL on palmitate-induced inflammation and insulin resistance. Moreover, METRNL augmented the mRNA expression of fatty acid oxidation-associated genes, such as carnitine palmitoyltransferase 1 (CPT1), acyl-CoA oxidase (ACO), and fatty acid binding protein 3 (FABP3). siRNAs for AMPK and PPARδ reversed these changes. In the current study, we report for the first time that METRNL alleviates inflammation and insulin resistance and induces fatty acid oxidation through AMPK or PPARδ-dependent signaling in skeletal muscle. SN - 2092-6413 UR - https://www.unboundmedicine.com/medline/citation/30213948/METRNL_attenuates_lipid_induced_inflammation_and_insulin_resistance_via_AMPK_or_PPARδ_dependent_pathways_in_skeletal_muscle_of_mice_ L2 - http://dx.doi.org/10.1038/s12276-018-0147-5 DB - PRIME DP - Unbound Medicine ER -