|MUSTRA RAKIC, JELENA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|LIU, CHUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|VEERAMACHANENI, SUDIPTA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|PAUL, LIGI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|CHEN, CHUNG-YEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|AUSMAN, LYNNE - Tufts University|
|WANG, XIANG-DONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Current Developments in Nutrition
Publication Type: Abstract Only
Publication Acceptance Date: 3/1/2019
Publication Date: 6/13/2019
Citation: Mustra Rakic, J., Liu, C., Veeramachaneni, S., Wu, D., Paul, L., Chen, C., Ausman, L.M., Wang, X. 2019. Modulation of reverse cholesterol transport by lycopene is associated with its protective role against cigarette smoke induced COPD and lung carcinogenesis in ferrets. [abstract]. Current Developments in Nutrition. 3(Suppl_1). Abstract No. OR05-02-19. https://doi.org/10.1093/cdn/nzz029.OR05-02-19.
Technical 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 (LXRa, PPARa, ABCA1 and ABCG1) as compared to NNK/CS group (P < 0.05). Additionally, HL feeding significantly increased protein levels of both nuclear hormone receptors, LXRalpha and PPARalpha, 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.