Modulation of Reverse Cholesterol Transport by Lycopene Is Associated with Its Protective Role Against Cigarette Smoke Induced COPD and Lung Carcinogenesis in Ferrets (OR05-02-19). (13th June 2019)

• Record Type: Journal Article
• Authors: Rakic, Jelena Mustra; Liu, Chun; Veeramachaneni, Sudipta; Wu, Dayong; Paul, Ligi; Chen, Oliver; Ausman, Lynne; Wang, Xiang-Dong
• Is Part Of: Current developments in nutrition. Volume 3(2019)Supplement 1
• Publication Date: 2019-06-13
• Subjects: Nutrition -- Periodicals; Nutritional Physiological Phenomena; Nutrition; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 612.3
• DOI: 10.1093/cdn/nzz029.OR05-02-19
• Languages: English
• ISSNs: 2475-2991

Abstract

Abstract: Objectives: Reverse cholesterol transport (RCT), which mediates removal of excess cholesterol from peripheral tissues, is a key player in persistent lung inflammation, a common feature of chronic obstructive pulmonary disease (COPD) and lung cancer, after cigarette smoke (CS) exposure. We have previously shown that lycopene, a carotenoid naturally occurring in tomatoes and tomato products, inhibits tobacco carcinogen (NNK)/CS-induced COPD and preneoplastic lesions in lung of ferrets, but the mechanism is unknown. We hypothesize that the protective role of lycopene against NNK/CS-induced COPD and lung preneoplastic lesions is associated with restoring the RCT in ferrets. Methods: Male ferrets (4 groups, n = 12−16/group) were exposed to combination of NNK and CS with or without lycopene feeding at low (LL) and high (HL) doses (equivalent to ∼30 mg and ∼90 mg lycopene/day in humans, respectively) for 22 weeks. Ferrets in NNK/CS groups were given NNK (50 mg/kg body weight, i.p. injection) once a month for 4 consecutive months, and were exposed to CS for 30 min/day for 22 weeks. The animals were fed lycopene or placebo starting three weeks prior to the NNK injections and continued until the end of the study. Results: NNK/CS exposure significantly increased total cholesterol levels in both plasma and lungs of ferrets ( P < 0.05), which was associated with COPD and lung preneoplastic lesion development. In lungs, HL and LL doses lowered NNK/CS-induced total cholesterol, with HL dose reaching significance ( P < 0.05); this was accompanied with the decreased lung lesions. HL group had significantly higher mRNA expression of critical genes involved in RCT ( LXRα, PPARα, ABCA1 and ABCG1) as compared to NNK/CS group ( P < 0.05). Additionally, HL feeding significantly increased protein levels of both nuclear hormone receptors, LXRα and PPARα, known regulators of ABCA1/G1 transporters ( P < 0.05). In plasma, lycopene restored total cholesterol and HDL-C concentrations to normal. Plasma triglyceride, LDL-C and VLDL-C concentrations were not significantly different between groups. Conclusions: These data demonstrate an important association between lycopene protection against NNK/CS induced lung lesions and pulmonary cholesterol homeostasis through the restoration of the impaired RCT. Funding Sources: NIH/NCI, USDA/ARS grants.