PMID- 31145942
OWN - NLM
STAT- MEDLINE
DCOM- 20200625
LR  - 20200625
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Linking)
VI  - 133
DP  - 2019 Aug
TI  - Sirt1 counteracts decrease in membrane phospholipid unsaturation and diastolic 
      dysfunction during saturated fatty acid overload.
PG  - 1-11
LID - S0022-2828(19)30110-5 [pii]
LID - 10.1016/j.yjmcc.2019.05.019 [doi]
AB  - BACKGROUND: The fatty acid (FA) composition of membrane phospholipid reflects at 
      least in part dietary fat composition. Saturated FA (SFA) suppress Sirt1 
      activity, while monounsaturated FA (MUFA) counteract this effect. OBJECTIVE: We 
      explored a role of Sirt1 in homeostatic control of the fatty acid composition of 
      membrane phospholipid in the presence of SFA overload. METHODS AND RESULTS: Sirt1 
      deficiency in cardiomyocytes decreased the expression levels of liver X receptor 
      (LXR)-target genes, particularly stearoyl-CoA desaturase-1 (Scd1), a 
      rate-limiting enzyme in the cellular synthesis of MUFA from SFA, increased 
      membrane SFA/MUFA ratio, and worsened left ventricular (LV) diastolic function in 
      mice fed an SFA-rich high fat diet. In cultured cardiomyocytes, Sirt1 knockdown 
      (KD) exacerbated the palmitate overload-induced increase in membrane SFA/MUFA 
      ratio, which was associated with decrease in the expression of LXR-target genes, 
      including Scd1. Forced overexpression of Scd1 in palmitate-overloaded Sirt1KD 
      cardiomyocytes lowered the SFA/MUFA ratio. Nicotinamide mononucleotide (NMN) 
      increased Sirt1 activity and Scd1 expression, thereby lowering membrane SFA/MUFA 
      ratio in palmitate-overloaded cardiomyocytes. These effects of NMN were not 
      observed for Scd1KD cardiomyocytes. LXRalpha/betaKD exacerbated palmitate 
      overload-induced increase in membrane SFA/MUFA ratio, while LXR agonist T0901317 
      alleviated it. NMN failed to rescue Scd1 protein expression and membrane SFA/MUFA 
      ratio in palmitate-overloaded LXRalpha/betaKD cardiomyocytes. The administration of NMN 
      or T0901317 showed a dramatic reversal in membrane SFA/MUFA ratio and LV 
      diastolic function in SFA-rich HFD-fed mice. CONCLUSION: Cardiac Sirt1 
      counteracted SFA overload-induced decrease in membrane phospholipid unsaturation 
      and diastolic dysfunction via regulating LXR-mediated transcription of the Scd1 
      gene.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Yamamoto, Tsunehisa
AU  - Yamamoto T
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
FAU - Endo, Jin
AU  - Endo J
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan; Japan 
      Science and Technology Agency, Tokyo, Japan.
FAU - Kataoka, Masaharu
AU  - Kataoka M
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
FAU - Matsuhashi, Tomohiro
AU  - Matsuhashi T
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
FAU - Katsumata, Yoshinori
AU  - Katsumata Y
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
FAU - Shirakawa, Kohsuke
AU  - Shirakawa K
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
FAU - Yoshida, Naohiro
AU  - Yoshida N
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan; 
      Department of Endocrinology and Hypertension, Tokyo Women's Medical University, 
      Tokyo, Japan.
FAU - Isobe, Sarasa
AU  - Isobe S
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
FAU - Moriyama, Hidenori
AU  - Moriyama H
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
FAU - Goto, Shinichi
AU  - Goto S
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
FAU - Yamashita, Kaoru
AU  - Yamashita K
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan; 
      Department of Endocrinology and Hypertension, Tokyo Women's Medical University, 
      Tokyo, Japan.
FAU - Ohto-Nakanishi, Takayo
AU  - Ohto-Nakanishi T
AD  - Lipidome Lab Co., Ltd., Akita, Japan.
FAU - Nakanishi, Hiroki
AU  - Nakanishi H
AD  - Lipidome Lab Co., Ltd., Akita, Japan; Research Center for Biosignal, Akita 
      University, Akita, Japan.
FAU - Shimanaka, Yuta
AU  - Shimanaka Y
AD  - Graduate School of Pharmaceutical Sciences, Tokyo University, Tokyo, Japan.
FAU - Kono, Nozomu
AU  - Kono N
AD  - Graduate School of Pharmaceutical Sciences, Tokyo University, Tokyo, Japan.
FAU - Shinmura, Ken
AU  - Shinmura K
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan; 
      Department of General Medicine, Hyogo College of Medicine, Hyogo, Japan.
FAU - Arai, Hiroyuki
AU  - Arai H
AD  - Graduate School of Pharmaceutical Sciences, Tokyo University, Tokyo, Japan.
FAU - Fukuda, Keiichi
AU  - Fukuda K
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
FAU - Sano, Motoaki
AU  - Sano M
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan; Japan 
      Science and Technology Agency, Tokyo, Japan. Electronic address: 
      msano@a8.keio.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190527
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Fatty Acids)
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Liver X Receptors)
RN  - 0 (Membrane Lipids)
RN  - 0 (Phospholipids)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - *Diastole
MH  - Diet, High-Fat
MH  - Disease Models, Animal
MH  - Disease Susceptibility
MH  - Fatty Acids/*metabolism
MH  - Fatty Acids, Monounsaturated/*metabolism
MH  - Lipid Metabolism
MH  - Liver X Receptors/agonists/metabolism
MH  - Membrane Lipids/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Myocytes, Cardiac/metabolism
MH  - Phospholipids/*metabolism
MH  - Sirtuin 1/genetics/*metabolism
MH  - Ventricular Dysfunction/etiology/*metabolism
OTO - NOTNLM
OT  - Diastolic dysfunction
OT  - Membrane fatty acid composition
OT  - Saturated fatty acid
OT  - Sirt1
OT  - Stearoyl-CoA desaturase-1
EDAT- 2019/05/31 06:00
MHDA- 2020/06/26 06:00
CRDT- 2019/05/31 06:00
PHST- 2019/04/18 00:00 [received]
PHST- 2019/05/21 00:00 [revised]
PHST- 2019/05/25 00:00 [accepted]
PHST- 2019/05/31 06:00 [pubmed]
PHST- 2020/06/26 06:00 [medline]
PHST- 2019/05/31 06:00 [entrez]
AID - S0022-2828(19)30110-5 [pii]
AID - 10.1016/j.yjmcc.2019.05.019 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2019 Aug;133:1-11. doi: 10.1016/j.yjmcc.2019.05.019. Epub 
      2019 May 27.