PMID- 30858489
OWN - NLM
STAT- MEDLINE
DCOM- 20200930
LR  - 20210109
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Mar 11
TI  - Skeletal Muscle-specific PGC-1alpha Overexpression Suppresses Atherosclerosis in 
      Apolipoprotein E-Knockout Mice.
PG  - 4077
LID - 10.1038/s41598-019-40643-1 [doi]
LID - 4077
AB  - Endurance exercise training prevents atherosclerosis. Peroxisome 
      proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) increases myokine 
      secretion from the skeletal muscle, and these myokines have been shown to affect 
      the function of multiple organs. Since endurance exercise training increases 
      PGC-1alpha expression in skeletal muscles, we investigated whether skeletal 
      muscle-specific PGC-1alpha overexpression suppresses atherosclerosis. Apolipoprotein 
      E-knockout (ApoE-KO)/PGC-1alpha mice, which overexpress PGC-1alpha in the skeletal muscle 
      of ApoE-KO mice, were sacrificed, and the atherosclerotic plaque area, 
      spontaneous activity, plasma lipid profile, and aortic gene expression were 
      measured. Immunohistochemical analyses were also performed. The atherosclerotic 
      lesions in ApoE-KO/PGC-1alpha mice were 40% smaller than those in ApoE-KO mice, 
      concomitant with the reduction in vascular cell adhesion molecule-1 (VCAM-1) and 
      monocyte chemoattractant protein-1 (MCP-1) mRNA and protein levels in the aorta. 
      Spontaneous activity and plasma lipid profiles were not changed by the 
      overexpression of PGC-1alpha in the skeletal muscle. In human umbilical vein 
      endothelial cells, Irisin and beta-aminoisobutyric acid (BAIBA), PGC-1alpha-dependent 
      myokines, inhibited the tumor necrosis factor alpha-induced VCAM-1 gene and protein 
      expression. BAIBA also inhibited TNFalpha-induced MCP-1 gene expression. These 
      results showed that the skeletal muscle-specific overexpression of PGC-1alpha 
      suppresses atherosclerosis and that PGC-1alpha-dependent myokines may be involved in 
      the preventive effects observed.
FAU - Shimba, Yuki
AU  - Shimba Y
AD  - Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and 
      Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 
      422-8526, Japan.
AD  - Research and Development Department, Tokai Hit Co., Ltd., 306-1 Gendoji-cho, 
      Fujinomiya-shi, Shizuoka, 418-0074, Japan.
FAU - Togawa, Hanako
AU  - Togawa H
AD  - Faculty of Social and Environmental Studies, Fuji Tokoha University, 325 Ohbuchi, 
      Fuji-shi, Shizuoka, 417-0801, Japan.
FAU - Senoo, Nanami
AU  - Senoo N
AD  - Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and 
      Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 
      422-8526, Japan.
AD  - Research Fellow of Japan Society for the Promotion of Science, 5-3-1 Kojimachi, 
      Chiyoda-ku, Tokyo, 102-0083, Japan.
FAU - Ikeda, Masahiko
AU  - Ikeda M
AD  - Graduate School of Environment and Disaster Research, Tokoha University, 325 
      Ohbuchi, Fuji-shi, Shizuoka, 417-0801, Japan.
FAU - Miyoshi, Noriyuki
AU  - Miyoshi N
AD  - Laboratory of Biochemistry, Graduate School of Nutritional and Environmental 
      Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, 
      Japan.
FAU - Morita, Akihito
AU  - Morita A
AD  - Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and 
      Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 
      422-8526, Japan.
FAU - Miura, Shinji
AU  - Miura S
AD  - Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and 
      Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 
      422-8526, Japan. miura@u-shizuoka-ken.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190311
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Aminoisobutyric Acids)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - T68ALE2O9F (3-aminoisobutyric acid)
SB  - IM
MH  - Aminoisobutyric Acids/pharmacology
MH  - Animals
MH  - Apolipoproteins E/*genetics
MH  - Atherosclerosis/drug therapy/*genetics/physiopathology/therapy
MH  - Chemokine CCL2/genetics
MH  - Disease Models, Animal
MH  - Endurance Training/methods
MH  - Gene Expression Regulation/genetics
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Skeletal/drug effects/*metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/*genetics
MH  - Physical Conditioning, Animal/physiology
MH  - Tumor Necrosis Factor-alpha/genetics
MH  - Vascular Cell Adhesion Molecule-1/genetics
PMC - PMC6411944
COIS- The authors declare no competing interests.
EDAT- 2019/03/13 06:00
MHDA- 2020/10/02 06:00
PMCR- 2019/03/11
CRDT- 2019/03/13 06:00
PHST- 2018/01/17 00:00 [received]
PHST- 2019/02/21 00:00 [accepted]
PHST- 2019/03/13 06:00 [entrez]
PHST- 2019/03/13 06:00 [pubmed]
PHST- 2020/10/02 06:00 [medline]
PHST- 2019/03/11 00:00 [pmc-release]
AID - 10.1038/s41598-019-40643-1 [pii]
AID - 40643 [pii]
AID - 10.1038/s41598-019-40643-1 [doi]
PST - epublish
SO  - Sci Rep. 2019 Mar 11;9(1):4077. doi: 10.1038/s41598-019-40643-1.