DEL-1 ameliorates high-fat diet-induced insulin resistance in mouse skeletal muscle through SIRT1/SERCA2-mediated ER stress suppression

Jaw Long Sun, Jinwoo Park, Taeseung Lee, Ji Hoon Jeong, Tae Woo Jung

Research output: Contribution to journalArticle

Abstract

Inflammation and endoplasmic reticulum (ER) stress are associated with the development of insulin resistance and diabetes. Developmental endothelial locus-1 (DEL-1) enhances efferocytosis by macrophage and suppresses inflammatory response. However, effects of DEL-1 on ER stress-mediated insulin resistance in skeletal muscle remain unclear. Here, DEL-1 treatment augmented SIRT1 expression in C2C12 myocytes, thereby increasing SERCA2 expression in a dose-dependent fashion, and attenuated ER stress and insulin resistance under palmitate treatment condition. SIRT1/SERCA2 knockdown abrogated effects of DEL-1 on palmitate-induced insulin resistance as well as ER stress. Pharmacological significance of DEL-1 was confirmed by in vivo experiments. DEL-1 administration suppressed ER stress, insulin resistance, and SIRT1/SERCA2 expression in skeletal muscle of high-fat diet (HFD)-fed mice. Additionally, siRNA transfection-mediated in vivo downregulation of SIRT1 suppressed the effects of DEL-1 on expression of SERCA2, ER stress, and insulin resistance in skeletal muscle of HFD-fed mice. DEL-1 attenuates palmitate-induced and HFD-induced skeletal muscle ER stress and insulin resistance via SIRT1/SERCA2-mediated signaling.

Original languageEnglish
Article number113730
JournalBiochemical Pharmacology
Volume171
DOIs
StatePublished - Jan 2020

Fingerprint

Endoplasmic Reticulum Stress
High Fat Diet
Nutrition
Muscle
Insulin Resistance
Skeletal Muscle
Fats
Insulin
Palmitates
Macrophages
Medical problems
Muscle Cells
Small Interfering RNA
Transfection
Down-Regulation
Pharmacology
Inflammation

Keywords

  • DEL-1
  • Endoplasmic reticulum stress
  • Insulin resistance
  • SERCA2
  • SIRT1

Cite this

@article{366d335ba6f54c939ef1eb5131b8e116,
title = "DEL-1 ameliorates high-fat diet-induced insulin resistance in mouse skeletal muscle through SIRT1/SERCA2-mediated ER stress suppression",
abstract = "Inflammation and endoplasmic reticulum (ER) stress are associated with the development of insulin resistance and diabetes. Developmental endothelial locus-1 (DEL-1) enhances efferocytosis by macrophage and suppresses inflammatory response. However, effects of DEL-1 on ER stress-mediated insulin resistance in skeletal muscle remain unclear. Here, DEL-1 treatment augmented SIRT1 expression in C2C12 myocytes, thereby increasing SERCA2 expression in a dose-dependent fashion, and attenuated ER stress and insulin resistance under palmitate treatment condition. SIRT1/SERCA2 knockdown abrogated effects of DEL-1 on palmitate-induced insulin resistance as well as ER stress. Pharmacological significance of DEL-1 was confirmed by in vivo experiments. DEL-1 administration suppressed ER stress, insulin resistance, and SIRT1/SERCA2 expression in skeletal muscle of high-fat diet (HFD)-fed mice. Additionally, siRNA transfection-mediated in vivo downregulation of SIRT1 suppressed the effects of DEL-1 on expression of SERCA2, ER stress, and insulin resistance in skeletal muscle of HFD-fed mice. DEL-1 attenuates palmitate-induced and HFD-induced skeletal muscle ER stress and insulin resistance via SIRT1/SERCA2-mediated signaling.",
keywords = "DEL-1, Endoplasmic reticulum stress, Insulin resistance, SERCA2, SIRT1",
author = "Sun, {Jaw Long} and Jinwoo Park and Taeseung Lee and Jeong, {Ji Hoon} and Jung, {Tae Woo}",
year = "2020",
month = "1",
doi = "10.1016/j.bcp.2019.113730",
language = "English",
volume = "171",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",

}

DEL-1 ameliorates high-fat diet-induced insulin resistance in mouse skeletal muscle through SIRT1/SERCA2-mediated ER stress suppression. / Sun, Jaw Long; Park, Jinwoo; Lee, Taeseung; Jeong, Ji Hoon; Jung, Tae Woo.

In: Biochemical Pharmacology, Vol. 171, 113730, 01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - DEL-1 ameliorates high-fat diet-induced insulin resistance in mouse skeletal muscle through SIRT1/SERCA2-mediated ER stress suppression

AU - Sun, Jaw Long

AU - Park, Jinwoo

AU - Lee, Taeseung

AU - Jeong, Ji Hoon

AU - Jung, Tae Woo

PY - 2020/1

Y1 - 2020/1

N2 - Inflammation and endoplasmic reticulum (ER) stress are associated with the development of insulin resistance and diabetes. Developmental endothelial locus-1 (DEL-1) enhances efferocytosis by macrophage and suppresses inflammatory response. However, effects of DEL-1 on ER stress-mediated insulin resistance in skeletal muscle remain unclear. Here, DEL-1 treatment augmented SIRT1 expression in C2C12 myocytes, thereby increasing SERCA2 expression in a dose-dependent fashion, and attenuated ER stress and insulin resistance under palmitate treatment condition. SIRT1/SERCA2 knockdown abrogated effects of DEL-1 on palmitate-induced insulin resistance as well as ER stress. Pharmacological significance of DEL-1 was confirmed by in vivo experiments. DEL-1 administration suppressed ER stress, insulin resistance, and SIRT1/SERCA2 expression in skeletal muscle of high-fat diet (HFD)-fed mice. Additionally, siRNA transfection-mediated in vivo downregulation of SIRT1 suppressed the effects of DEL-1 on expression of SERCA2, ER stress, and insulin resistance in skeletal muscle of HFD-fed mice. DEL-1 attenuates palmitate-induced and HFD-induced skeletal muscle ER stress and insulin resistance via SIRT1/SERCA2-mediated signaling.

AB - Inflammation and endoplasmic reticulum (ER) stress are associated with the development of insulin resistance and diabetes. Developmental endothelial locus-1 (DEL-1) enhances efferocytosis by macrophage and suppresses inflammatory response. However, effects of DEL-1 on ER stress-mediated insulin resistance in skeletal muscle remain unclear. Here, DEL-1 treatment augmented SIRT1 expression in C2C12 myocytes, thereby increasing SERCA2 expression in a dose-dependent fashion, and attenuated ER stress and insulin resistance under palmitate treatment condition. SIRT1/SERCA2 knockdown abrogated effects of DEL-1 on palmitate-induced insulin resistance as well as ER stress. Pharmacological significance of DEL-1 was confirmed by in vivo experiments. DEL-1 administration suppressed ER stress, insulin resistance, and SIRT1/SERCA2 expression in skeletal muscle of high-fat diet (HFD)-fed mice. Additionally, siRNA transfection-mediated in vivo downregulation of SIRT1 suppressed the effects of DEL-1 on expression of SERCA2, ER stress, and insulin resistance in skeletal muscle of HFD-fed mice. DEL-1 attenuates palmitate-induced and HFD-induced skeletal muscle ER stress and insulin resistance via SIRT1/SERCA2-mediated signaling.

KW - DEL-1

KW - Endoplasmic reticulum stress

KW - Insulin resistance

KW - SERCA2

KW - SIRT1

UR - http://www.scopus.com/inward/record.url?scp=85075721340&partnerID=8YFLogxK

U2 - 10.1016/j.bcp.2019.113730

DO - 10.1016/j.bcp.2019.113730

M3 - Article

C2 - 31778646

AN - SCOPUS:85075721340

VL - 171

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

M1 - 113730

ER -