PMID- 28199134
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20220408
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 56
IP  - 6
DP  - 2017 Jun
TI  - Genetic Control of Fatty Acid beta-Oxidation in Chronic Obstructive Pulmonary 
      Disease.
PG  - 738-748
LID - 10.1165/rcmb.2016-0282OC [doi]
AB  - Bioenergetics homeostasis is important for cells to sustain normal functions and 
      defend against injury. The genetic controls of bioenergetics homeostasis, 
      especially lipid metabolism, remain poorly understood in chronic obstructive 
      pulmonary disease (COPD), the third leading cause of death in the world. 
      Additionally, the biological function of most of the susceptibility genes 
      identified from genome-wide association studies (GWASs) in COPD remains unclear. 
      Here, we aimed to address (1) how fatty acid oxidation (FAO), specifically 
      beta-oxidation, a key lipid metabolism pathway that provides energy to cells, 
      contributes to cigarette smoke (CS)-induced COPD; and (2) whether-and if so, 
      how-FAM13A (family with sequence similarity 13 member A), a well-replicated COPD 
      GWAS gene, modulates the FAO pathway. We demonstrated that CS induced expression 
      of carnitine palmitoyltransferase 1A (CPT1A), a key mitochondrial enzyme for the 
      FAO pathway, thereby enhancing FAO. Pharmacological inhibition of FAO by etomoxir 
      blunted CS-induced reactive oxygen species accumulation and cell death in lung 
      epithelial cells. FAM13A promoted FAO, possibly by interacting with and 
      activating sirutin 1, and increasing expression of CPT1A. Furthermore, CS-induced 
      cell death was reduced in lungs from Fam13a(-/-) mice. Our results suggest that 
      FAM13A, the COPD GWAS gene, shapes the cellular metabolic response to CS exposure 
      by promoting the FAO pathway, which may contribute to COPD development.
FAU - Jiang, Zhiqiang
AU  - Jiang Z
AD  - 1 Channing Division of Network Medicine and.
FAU - Knudsen, Nelson H
AU  - Knudsen NH
AD  - Departments of 2 Genetics and Complex Diseases, and.
AD  - 3 Nutrition, Division of Biological Sciences, Harvard T. H. Chan School of Public 
      Health, Boston, Massachusetts, and.
FAU - Wang, Gang
AU  - Wang G
AD  - 4 Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.
FAU - Qiu, Weiliang
AU  - Qiu W
AD  - 1 Channing Division of Network Medicine and.
FAU - Naing, Zun Zar Chi
AU  - Naing ZZC
AD  - 1 Channing Division of Network Medicine and.
FAU - Bai, Yan
AU  - Bai Y
AD  - 5 Division of Pulmonary and Critical Care Medicine, Department of Medicine, 
      Brigham and Women's Hospital and Harvard Medical School.
FAU - Ai, Xingbin
AU  - Ai X
AD  - 5 Division of Pulmonary and Critical Care Medicine, Department of Medicine, 
      Brigham and Women's Hospital and Harvard Medical School.
FAU - Lee, Chih-Hao
AU  - Lee CH
AD  - Departments of 2 Genetics and Complex Diseases, and.
AD  - 3 Nutrition, Division of Biological Sciences, Harvard T. H. Chan School of Public 
      Health, Boston, Massachusetts, and.
FAU - Zhou, Xiaobo
AU  - Zhou X
AUID- ORCID: 0000-0002-7127-2869
AD  - 1 Channing Division of Network Medicine and.
AD  - 5 Division of Pulmonary and Critical Care Medicine, Department of Medicine, 
      Brigham and Women's Hospital and Harvard Medical School.
LA  - eng
GR  - R01 HL127200/HL/NHLBI NIH HHS/United States
GR  - R33 HL120794/HL/NHLBI NIH HHS/United States
GR  - T32 HL007035/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Fatty Acids)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.3.1.21 (CPT1A protein, human)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
CIN - doi: 10.1165/rcmb.2017-0080ED
MH  - Acetylation
MH  - Animals
MH  - Bronchi/pathology
MH  - Carnitine O-Palmitoyltransferase/metabolism
MH  - Cell Death
MH  - Cell Respiration
MH  - Epithelial Cells/metabolism
MH  - Fatty Acids/*metabolism
MH  - GTPase-Activating Proteins/metabolism
MH  - Gene Silencing
MH  - Humans
MH  - Mice, Inbred C57BL
MH  - Mitochondria/metabolism
MH  - Oxidation-Reduction
MH  - Protein Binding
MH  - Pulmonary Disease, Chronic Obstructive/*genetics
MH  - Reactive Oxygen Species/metabolism
MH  - Sirtuin 1/metabolism
MH  - Smoking/adverse effects
PMC - PMC5516290
OTO - NOTNLM
OT  - CPT1A
OT  - FAM13A
OT  - cigarette smoke
OT  - fatty acid beta-oxidation
OT  - mitochondria
EDAT- 2017/02/16 06:00
MHDA- 2017/08/02 06:00
PMCR- 2018/06/01
CRDT- 2017/02/16 06:00
PHST- 2017/02/16 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
PHST- 2017/02/16 06:00 [entrez]
PHST- 2018/06/01 00:00 [pmc-release]
AID - 10.1165/rcmb.2016-0282OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2017 Jun;56(6):738-748. doi: 10.1165/rcmb.2016-0282OC.