{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:27:36Z","timestamp":1788870456339,"version":"build-2803163510"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 \u03b2-oxidation, a key lipid metabolism pathway that provides energy to cells, contributes to cigarette smoke (CS)-induced COPD; and (2) whether\u2014and if so, how\u2014FAM13A (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\u2212\/\u2212 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.<\/jats:p>","DOI":"10.1165\/rcmb.2016-0282oc","type":"journal-article","created":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T15:44:36Z","timestamp":1487173476000},"page":"738-748","source":"Crossref","is-referenced-by-count":65,"title":["Genetic Control of Fatty Acid \u03b2-Oxidation in Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"56","author":[{"given":"Zhiqiang","family":"Jiang","sequence":"first","affiliation":[{"name":"Channing Division of Network Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson H.","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Complex Diseases, and"},{"name":"Nutrition, Division of Biological Sciences, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiliang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zun Zar Chi","family":"Naing","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Bai","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingbin","family":"Ai","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hao","family":"Lee","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Complex Diseases, and"},{"name":"Nutrition, Division of Biological Sciences, Harvard T. 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Chan School of Public Health, Boston, Massachusetts, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7127-2869","authenticated-orcid":false,"given":"Xiaobo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine and"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,6,1]]},"reference":[{"key":"2026021122422423500_bib1","first-page":"1","article-title":"Deaths: preliminary data for 2008","volume":"59","author":"Mini\u00f1o","year":"2011","journal-title":"Natl Vital Stat Rep"},{"key":"2026021122422423500_bib2","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1172\/JCI60324","article-title":"Pathogenesis of chronic obstructive pulmonary disease","volume":"122","author":"Tuder","year":"2012","journal-title":"J Clin Invest"},{"key":"2026021122422423500_bib3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1385\/CBB:43:1:167","article-title":"Oxidative stress in pathogenesis of chronic obstructive pulmonary disease: cellular and molecular mechanisms","volume":"43","author":"Rahman","year":"2005","journal-title":"Cell Biochem Biophys"},{"key":"2026021122422423500_bib4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.rmed.2011.11.003","article-title":"The effects of cigarette smoke on airway inflammation in asthma and COPD: therapeutic implications","volume":"106","author":"Tamimi","year":"2012","journal-title":"Respir Med"},{"key":"2026021122422423500_bib5","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/15412550701603775","article-title":"Functional significance of apoptosis in chronic obstructive pulmonary disease","volume":"4","author":"Park","year":"2007","journal-title":"COPD"},{"key":"2026021122422423500_bib6","doi-asserted-by":"crossref","first-page":"18880","DOI":"10.1073\/pnas.1005574107","article-title":"Autophagy protein microtubule-associated protein 1 light chain-3B (LC3B) activates extrinsic apoptosis during cigarette smoke-induced emphysema","volume":"107","author":"Chen","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026021122422423500_bib7","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1586\/17476348.2013.834252","article-title":"Mitochondria in lung diseases","volume":"7","author":"Aravamudan","year":"2013","journal-title":"Expert Rev Respir Med"},{"key":"2026021122422423500_bib8","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1016\/j.biochi.2012.03.006","article-title":"Leptin, adiponectin and pulmonary diseases","volume":"94","author":"Ali Assad","year":"2012","journal-title":"Biochimie"},{"key":"2026021122422423500_bib9","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1159\/000369990","article-title":"Serum leptin and skeletal differences between obese and non-obese patients with chronic obstructive pulmonary disease","volume":"7","author":"Kor\u0161i\u0107","year":"2014","journal-title":"Obes Facts"},{"key":"2026021122422423500_bib10","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1513\/AnnalsATS.201501-005OC","article-title":"Association of plasma adipokines with chronic obstructive pulmonary disease severity and progression","volume":"12","author":"Oh","year":"2015","journal-title":"Ann Am Thorac Soc"},{"key":"2026021122422423500_bib11","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1164\/rccm.201312-2210OC","article-title":"Untargeted lipidomic analysis in chronic obstructive pulmonary disease. 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