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Mouse Models to Study Antiobesogenic Effects of Carotenoids

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Book cover Plant and Food Carotenoids

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2083))

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Abstract

Carotenoids entail a vast potential to tackle health problems including obesity and some of its comorbidities. The use of animal models remains necessary, particularly at early stages of research (preclinical) and for advancing in mechanistic aspects of carotenoid action. No single animal model completely mimics human absorption and metabolism of carotenoids, and the best model must be chosen considering the specific application, characteristics of the individual models, and funding and facilities available. Here, we propose three protocols in mice to investigate the potential of a given carotenoid, carotenoid mixture, or carotenoid-rich extract to (a) counteract the development of obesity and prevent the metabolic alterations caused by feeding mice a moderate high-fat diet; (b) improve the metabolic profile of obese animals with metabolic alterations caused by chronic high-fat diet feeding; and (c) act as coadjuvants in weight loss strategies (reversion to a low fat diet) applied to diet-induced obese animals.

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References

  1. Palou A, Picó C, Bonet ML (2003) The molecular basis of body weight control. Forum Nutr 56:164–168

    CAS  PubMed  Google Scholar 

  2. Scully T (2014) Public health: society at large. Nature 508(7496):S50–S51. https://doi.org/10.1038/508S50a

    Article  CAS  PubMed  Google Scholar 

  3. Shao A, Drewnowski A, Willcox DC, Krämer L, Lausted C, Eggersdorfer M, Mathers J, Bell JD, Randolph RK, Witkamp R, Griffiths JC (2017) Optimal nutrition and the ever-changing dietary landscape: a conference report. Eur J Nutr 56(Suppl 1):1–21. https://doi.org/10.1007/s00394-017-1460-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Vasileva LV, Marchev AS, Georgiev MI (2018) Causes and solutions to “globesity”: the new fa(s)t alarming global epidemic. Food Chem Toxicol 121:173–193. https://doi.org/10.1016/j.fct.2018.08.071

    Article  CAS  PubMed  Google Scholar 

  5. Lumeng CN, Saltiel AR (2011) Inflammatory links between obesity and metabolic disease. J Clin Invest 121(6):2111–2117. https://doi.org/10.1172/JCI57132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Isolauri E (2017) Microbiota and obesity. Nestle Nutr Inst Workshop Ser 88:95–105. https://doi.org/10.1159/000455217

    Article  PubMed  Google Scholar 

  7. Bonet ML, Canas JA, Ribot J, Palou A (2015) Carotenoids and their conversion products in the control of adipocyte function, adiposity and obesity. Arch Biochem Biophys 572:112–125. https://doi.org/10.1016/j.abb.2015.02.022

    Article  CAS  PubMed  Google Scholar 

  8. Bonet ML, Canas JA, Ribot J, Palou A (2016) Carotenoids in adipose tissue biology and obesity. Subcell Biochem 79:377–414. https://doi.org/10.1007/978-3-319-39126-7_15

    Article  CAS  PubMed  Google Scholar 

  9. Rodriguez-Concepcion M, Avalos J, Bonet ML, Boronat A, Gomez-Gomez L, Hornero-Mendez D, Limon MC, Meléndez-Martínez AJ, Olmedilla-Alonso B, Palou A, Ribot J, Rodrigo MJ, Zacarias L, Zhu C (2018) A global perspective on carotenoids: metabolism, biotechnology, and benefits for nutrition and health. Prog Lipid Res 70:62–93. https://doi.org/10.1016/j.plipres.2018.04.004

    Article  CAS  PubMed  Google Scholar 

  10. Lee CM, Boileau AC, Boileau TW, Williams AW, Swanson KS, Heintz KA, Erdman JW (1999) Review of animal models in carotenoid research. J Nutr 129(12):2271–2277. https://doi.org/10.1093/jn/129.12.2271

    Article  CAS  PubMed  Google Scholar 

  11. Palczewski G, Widjaja-Adhi MA, Amengual J, Golczak M, von Lintig J (2016) Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism. J Lipid Res 57(9):1684–1695. https://doi.org/10.1194/jlr.M069021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Amengual J, Gouranton E, van Helden YG, Hessel S, Ribot J, Kramer E, Kiec-Wilk B, Razny U, Lietz G, Wyss A, Dembinska-Kiec A, Palou A, Keijer J, Landrier JF, Bonet ML, von Lintig J (2011) Beta-carotene reduces body adiposity of mice via BCMO1. PLoS One 6(6):e20644. https://doi.org/10.1371/journal.pone.0020644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Musinovic H, Bonet ML, Granados N, Amengual J, von Lintig J, Ribot J, Palou A (2014) Beta-carotene during the suckling period is absorbed intact and induces retinoic acid dependent responses similar to preformed vitamin a in intestine and liver, but not adipose tissue of young rats. Mol Nutr Food Res 58 (11):2157–2165. doi:https://doi.org/10.1002/mnfr.201400457

  14. Granados N, Amengual J, Ribot J, Musinovic H, Ceresi E, von Lintig J, Palou A, Bonet ML (2013) Vitamin a supplementation in early life affects later response to an obesogenic diet in rats. Int J Obes 37(9):1169–1176. https://doi.org/10.1038/ijo.2012.190

    Article  CAS  Google Scholar 

  15. Arreguín A, Ribot J, Mušinović H, von Lintig J, Palou A, Bonet ML (2018) Dietary vitamin a impacts DNA methylation patterns of adipogenesis-related genes in suckling rats. Arch Biochem Biophys 650:75–84. https://doi.org/10.1016/j.abb.2018.05.009

    Article  CAS  PubMed  Google Scholar 

  16. Nilsson C, Raun K, Yan FF, Larsen MO, Tang-Christensen M (2012) Laboratory animals as surrogate models of human obesity. Acta Pharmacol Sin 33(2):173–181. https://doi.org/10.1038/aps.2011.203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Panchal SK, Poudyal H, Iyer A, Nazer R, Alam MA, Diwan V, Kauter K, Sernia C, Campbell F, Ward L, Gobe G, Fenning A, Brown L (2011) High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol 57(5):611–624. https://doi.org/10.1097/FJC.0b013e31821b1379

    Article  CAS  PubMed  Google Scholar 

  18. Panchal SK, Brown L (2011) Rodent models for metabolic syndrome research. J Biomed Biotechnol 2011:351982. https://doi.org/10.1155/2011/351982

    Article  PubMed  Google Scholar 

  19. Lai M, Chandrasekera PC, Barnard ND (2014) You are what you eat, or are you? The challenges of translating high-fat-fed rodents to human obesity and diabetes. Nutr Diabetes 4:e135. https://doi.org/10.1038/nutd.2014.30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ventura LL, Fortes NC, Santiago HC, Caliari MV, Gomes MA, Oliveira DR (2017) Obesity-induced diet leads to weight gain, systemic metabolic alterations, adipose tissue inflammation, hepatic steatosis, and oxidative stress in gerbils. PeerJ 5:e2967. https://doi.org/10.7717/peerj.2967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mustonen AM, Puukka M, Rouvinen-Watt K, Aho J, Asikainen J, Nieminen P (2009) Response to fasting in an unnaturally obese carnivore, the captive European polecat Mustela putorius. Exp Biol Med (Maywood) 234(11):1287–1295. https://doi.org/10.3181/0904-RM-140

    Article  CAS  Google Scholar 

  22. Hinney A, Vogel CI, Hebebrand J (2010) From monogenic to polygenic obesity: recent advances. Eur Child Adolesc Psychiatry 19(3):297–310. https://doi.org/10.1007/s00787-010-0096-6

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rosini TC, Silva AS (1992) Moraes C (2012) diet-induced obesity: rodent model for the study of obesity-related disorders. Rev Assoc Med Bras 58(3):383–387

    Google Scholar 

  24. Petrov PD, Ribot J, Palou A, Bonet ML (2015) Improved metabolic regulation is associated with retinoblastoma protein gene haploinsufficiency in mice. Am J Physiol Endocrinol Metab 308(2):E172–E183. https://doi.org/10.1152/ajpendo.00308.2014

    Article  CAS  PubMed  Google Scholar 

  25. Marquardt N, Feja M, Hünigen H, Plendl J, Menken L, Fink H, Bert B (2018) Euthanasia of laboratory mice: are isoflurane and sevoflurane real alternatives to carbon dioxide? PLoS One 13(9):e0203793. https://doi.org/10.1371/journal.pone.0203793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Reynés B, Serrano A, Petrov PD, Ribot J, Chetrit C, Martínez-Puig D, Bonet ML, Palou A (2016) Anti-obesity and insulin-sensitising effects of a glycosaminoglycan mix. J Funct Foods 26:350–362. https://doi.org/10.1016/j.jff.2016.07.022

    Article  CAS  Google Scholar 

  27. Rodriguez E, Ribot J, Rodriguez AM, Palou A (2004) PPAR-gamma 2 expression in response to cafeteria diet: gender- and depot-specific effects. Obes Res 12(9):1455–1463. https://doi.org/10.1038/oby.2004.182

    Article  CAS  PubMed  Google Scholar 

  28. Ribot J, Rodríguez AM, Rodríguez E, Palou A (2008) Adiponectin and resistin response in the onset of obesity in male and female rats. Obesity (Silver Spring) 16(4):723–730. https://doi.org/10.1038/oby.2008.113

    Article  CAS  Google Scholar 

  29. Reynés B, García-Ruiz E, Díaz-Rúa R, Palou A, Oliver P (2014) Reversion to a control balanced diet is able to restore body weight and to recover altered metabolic parameters in adult rats long-term fed on a cafeteria diet. Food Res Int 64:839–848. https://doi.org/10.1016/j.foodres.2014.08.012

    Article  CAS  PubMed  Google Scholar 

  30. Sato Mito N, Suzui M, Yoshino H, Kaburagi T, Sato K (2009) Long term effects of high fat and sucrose diets on obesity and lymphocyte proliferation in mice. J Nutr Health Aging 13(7):602–606

    Article  CAS  PubMed  Google Scholar 

  31. Surwit RS, Feinglos MN, Rodin J, Sutherland A, Petro AE, Opara EC, Kuhn CM, Rebuffé-Scrive M (1995) Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and a/J mice. Metabolism 44(5):645–651

    Article  CAS  PubMed  Google Scholar 

  32. Buettner R, Schölmerich J, Bollheimer LC (2007) High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity (Silver Spring) 15(4):798–808. https://doi.org/10.1038/oby.2007.608

    Article  CAS  Google Scholar 

  33. Krishnan S, Cooper JA (2014) Effect of dietary fatty acid composition on substrate utilization and body weight maintenance in humans. Eur J Nutr 53(3):691–710. https://doi.org/10.1007/s00394-013-0638-z

    Article  CAS  PubMed  Google Scholar 

  34. Voigt A, Ribot J, Sabater AG, Palou A, Bonet ML, Klaus S (2015) Identification of Mest/Peg1 gene expression as a predictive biomarker of adipose tissue expansion sensitive to dietary anti-obesity interventions. Genes Nutr 10(5):477. https://doi.org/10.1007/s12263-015-0477-z

    Article  CAS  Google Scholar 

  35. Voigt A, Agnew K, van Schothorst EM, Keijer J, Klaus S (2013) Short-term, high fat feeding-induced changes in white adipose tissue gene expression are highly predictive for long-term changes. Mol Nutr Food Res 57(8):1423–1434. https://doi.org/10.1002/mnfr.201200671

    Article  CAS  PubMed  Google Scholar 

  36. Margareto J, Gómez-Ambrosi J, Marti A, Martínez JA (2001) Time-dependent effects of a high-energy-yielding diet on the regulation of specific white adipose tissue genes. Biochem Biophys Res Commun 283(1):6–11. https://doi.org/10.1006/bbrc.2001.4733

    Article  CAS  PubMed  Google Scholar 

  37. Ciapaite J, van den Broek NM, Te Brinke H, Nicolay K, Jeneson JA, Houten SM, Prompers JJ (2011) Differential effects of short- and long-term high-fat diet feeding on hepatic fatty acid metabolism in rats. Biochim Biophys Acta 1811(7–8):441–451. https://doi.org/10.1016/j.bbalip.2011.05.005

    Article  CAS  PubMed  Google Scholar 

  38. Li CC, Liu C, Fu M, Hu KQ, Aizawa K, Takahashi S, Hiroyuki S, Cheng J, von Lintig J, Wang XD (2018) Tomato powder inhibits hepatic Steatosis and inflammation potentially through restoring SIRT1 activity and Adiponectin function independent of carotenoid cleavage enzymes in mice. Mol Nutr Food Res 62(8):e1700738. doi:https://doi.org/10.1002/mnfr.201700738

  39. de Castro UG, dos Santos RA, Silva ME, de Lima WG, Campagnole-Santos MJ, Alzamora AC (2013) Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats. Lipids Health Dis 12:136. https://doi.org/10.1186/1476-511X-12-136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Amengual J, Lobo GP, Golczak M, Li HN, Klimova T, Hoppel CL, Wyss A, Palczewski K, von Lintig J (2011) A mitochondrial enzyme degrades carotenoids and protects against oxidative stress. FASEB J 25(3):948–959. https://doi.org/10.1096/fj.10-173906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hessel S, Eichinger A, Isken A, Amengual J, Hunzelmann S, Hoeller U, Elste V, Hunziker W, Goralczyk R, Oberhauser V, von Lintig J, Wyss A (2007) CMO1 deficiency abolishes vitamin a production from beta-carotene and alters lipid metabolism in mice. J Biol Chem 282(46):33553–33561. https://doi.org/10.1074/jbc.M706763200

    Article  CAS  PubMed  Google Scholar 

  42. West DB, Waguespack J, McCollister S (1995) Dietary obesity in the mouse: interaction of strain with diet composition. Am J Phys 268(3 Pt 2):R658–R665. https://doi.org/10.1152/ajpregu.1995.268.3.R658

    Article  CAS  Google Scholar 

  43. Reusch JEB, Kumar TR, Regensteiner JG, Zeitler PS, Participants C (2018) Identifying the critical gaps in research on sex differences in metabolism across the life span. Endocrinology 159(1):9–19. https://doi.org/10.1210/en.2017-03019

    Article  PubMed  Google Scholar 

  44. Priego T, Sanchez J, Pico C, Palou A (2008) Sex-differential expression of metabolism-related genes in response to a high-fat diet. Obesity (Silver Spring) 16(4):819–826. https://doi.org/10.1038/oby.2007.117

    Article  CAS  Google Scholar 

  45. Lobo GP, Hessel S, Eichinger A, Noy N, Moise AR, Wyss A, Palczewski K, von Lintig J (2010) ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin a production. FASEB J 24(6):1656–1666. https://doi.org/10.1096/fj.09-150995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Murano I, Morroni M, Zingaretti MC, Oliver P, Sanchez J, Fuster A, Pico C, Palou A, Cinti S (2005) Morphology of ferret subcutaneous adipose tissue after 6-month daily supplementation with oral beta-carotene. Biochim Biophys Acta 1740(2):305–312. https://doi.org/10.1016/j.bbadis.2004.10.012

    Article  CAS  PubMed  Google Scholar 

  47. Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22(3):659–661. https://doi.org/10.1096/fj.07-9574LSF

    Article  CAS  PubMed  Google Scholar 

  48. Blanchard OL, Smoliga JM (2015) Translating dosages from animal models to human clinical trials--revisiting body surface area scaling. FASEB J 29(5):1629–1634. https://doi.org/10.1096/fj.14-269043

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

BS is the recipient of a “La Caixa” Foundation predoctoral contract at the University of Balearic Islands. The group is a member of the European COST-Action EUROCAROTEN (CA15136; EU Framework Programme Horizon 2020), and the Spanish Network of Excellence CaRed (BIO2015-71703-REDT and BIO2017-90877-REDT; Agencia Estatal de Investigación, MICIU/FEDER, EU). CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn) is an initiative of the ISCIII (Spanish Government).

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Ribot, J., Stojnic, B., Palou, A., Bonet, M.L. (2020). Mouse Models to Study Antiobesogenic Effects of Carotenoids. In: Rodríguez-Concepción, M., Welsch, R. (eds) Plant and Food Carotenoids. Methods in Molecular Biology, vol 2083. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9952-1_30

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  • DOI: https://doi.org/10.1007/978-1-4939-9952-1_30

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