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CD36 mRNA in the Gastrointestinal Tract Is Differentially Regulated by Dietary Fat Intake in Obesity-Prone and Obesity-Resistant Rats

Abstract

Background

The gastrointestinal tract (GI) is important for detection and transport of consumed nutrients and has been implicated in susceptibility to diet-induced obesity in various rat strains.

Aims

The current studies investigated the regulation of CD36, a receptor which facilitates uptake of long-chain fatty acids, in the GI tract of obesity-prone Osborne–Mendel and obesity-resistant S5B rats fed a high-fat diet.

Methods

Osborne–Mendel and S5B rats consumed a high-fat diet (HFD, 55 % kcal from fat) or a low-fat diet (10 % kcal from fat) for either 3 or 14 days. CD36 messenger RNA (mRNA) levels were measured from circumvallate papillae of the tongue and from duodenal enterocytes.

Results

In Osborne–Mendel rats, consumption of HFD for 3 and 14 days led to an increase in CD36 mRNA on circumvallate papillae and in duodenal enterocytes. CD36 mRNA levels were positively correlated with body weight gain and kilocalories consumed at 3 days. In S5B rats, consumption of HFD for 3 days did not alter CD36 mRNA levels on circumvallate papillae or in the duodenum. Duodenal CD36 levels were elevated in S5B rats following 14 days of HFD consumption. CD36 mRNA levels in the duodenum were positively correlated with body weight gain and kilocalories consumed at 14 days.

Conclusions

These data support the differential sensing of nutrients by two regions of the GI tract of obesity-prone and obesity-resistant rats consuming HFD and suggest a role for CD36 in the strain-specific susceptibility to obesity.

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References

  1. Barnes MJ, Holmes G, Primeaux SD, York DA, Bray GA. Increased expression of mu opioid receptors in animals susceptible to diet-induced obesity. Peptides. 2006;27:3292–3298.

    Article  PubMed  CAS  Google Scholar 

  2. Greenberg D, McCaffery J, Potack JZ, Bray GA, York DA. Differential satiating effects of fats in the small intestine of obesity-resistant and obesity-prone rats. Physiol Behav. 1999;66:621–626.

    Article  PubMed  CAS  Google Scholar 

  3. Ishihara Y, White CL, Kageyama H, Kageyama A, York DA, Bray GA. Effects of diet and time of the day on serum and CSF leptin levels in Osborne-Mendel and S5B/Pl rats. Obes Res. 2004;12:1067–1076.

    Article  PubMed  CAS  Google Scholar 

  4. Liu X, York DA, Bray GA. Regulation of Ghrelin gene expression in stomach and feeding response to a Ghrelin analogue in two strains of rats. Peptides. 2004;25:2171–2177.

    Article  PubMed  CAS  Google Scholar 

  5. Petrescu O, Cheema AF, Fan X, Bradbury MW, Berk PD. Differences in adiposyte long chain fatty acid uptake in Osborne-Mendel and S5B/Pl rats in response to high-fat diets. Int J Obes. 2008;32:853–862.

    Article  CAS  Google Scholar 

  6. Pittman D, Smith KR, Crawley ME, et al. Orosensory detection of fatty acids by obesity-prone and obesity-resistant rats: strain and sex differences. Chem Senses. 2008;33:449–460.

    Article  PubMed  CAS  Google Scholar 

  7. Primeaux SD, Barnes MJ, Bray GA. Olfactory bulbectomy increases food intake and hypothalamic neuropeptide Y in obesity-prone, but not obesity-resistant rats. Behav Brain Res. 2007;180:190–196.

    Article  PubMed  CAS  Google Scholar 

  8. Primeaux SD, Barnes MJ, Braymer HD, Bray GA. Sensitivity to the satiating effects of Exendin 4 is decreased in obesity-prone Osborne-Mendel rats compared to obesity-resistant S5B/Pl rats. Int J Obes. 2010;34:1427–1433.

    Article  CAS  Google Scholar 

  9. Gilbertson TA, Liu L, York DA, Bray GA. Dietary fat preferences are inversely correlated with peripheral gustatory fatty acid sensitivity. Ann N Y Acad Sci. 1998;855:165–168.

    Article  PubMed  CAS  Google Scholar 

  10. Bonen A, Holloway GP, Tandon NN, et al. Cardiac and skeletal muscle faty acid transport and transporters and triacylglycerol and fatty acid oxidation in lean and Zucker diabetic fatty rats. Am J Physiol Regul Integrat Comp Physiol. 2009;297:R1202–R1212.

    Article  CAS  Google Scholar 

  11. Moore KJ, El Khoury J, Medeiros LA, et al. A CD36-initiated signaling cascade mediate inflammatory effects of beta-amyloid. J Biol Chem. 2002;277:47373–47379.

    Article  PubMed  CAS  Google Scholar 

  12. Coburn CT, Knapp FF, Febbraio M, Beets AL, Silverstein RL, Abumrad NA. Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice. J Biol Chem. 2000;275:32523–32529.

    Article  PubMed  CAS  Google Scholar 

  13. Febbraio M, Silverstein RL. CD36: implications in cardiovascular disease. Int J Biochem Cell Biol. 2007;39:2012–2030.

    Article  PubMed  CAS  Google Scholar 

  14. Abumrad NA. CD36 may determine our desire for dietary fats. J Clin Invest. 2005;115:2965–2967.

    Article  PubMed  CAS  Google Scholar 

  15. Febbraio M, Abumrad NA, Hajjar DP, et al. A null mutation in murine CD36 reveals an importnt role in fatty acid and lipoprotein metabolism. J Biol Chem. 1999;274:19055–19062.

    Article  PubMed  CAS  Google Scholar 

  16. Febbraio M, Guy E, Coburn C, et al. The impact of overexpression and deficiency of fatty acid traslocase (FAT)/CD36. Mol Cell Biochem. 2002;239:193–197.

    Article  PubMed  CAS  Google Scholar 

  17. Gaillard D, Laugerette F, Darcel N, et al. The gustatory pathway is involved in CD36-mediated orosensory perception of long-chain fatty acids in the mouse. FASEB J. 2008;22:1458–1468.

    Article  PubMed  CAS  Google Scholar 

  18. Hajri T, Hall AM, Jensen DR, et al. CD36-facilitated fatty acid uptake inhibits leptin production and signaling in adipose tissue. Diabetes. 2008;56:1872–1880.

    Article  Google Scholar 

  19. Laugerette F, Passilly-Degrace P, Patris B, et al. CD36 involvement in orosensory detection of dietary lipids, spontaneous fat preference, and digestive secretions. J Clin Invest. 2005;115:3177–3184.

    Article  PubMed  CAS  Google Scholar 

  20. Sclafani A, Ackroff K, Abumrad NA. CD36 gene deletion reduces fat preference and intake but not post-oral fat conditioning in mice. Am J Physiol Regulat Integ Comp Physiol. 2007;293:R1823–R1832.

    Article  CAS  Google Scholar 

  21. Hofer D, Puschel B, Drenckhahn D. Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin. Proc Natl Acad Sci U S A. 1996;93:6631–6634.

    Article  PubMed  CAS  Google Scholar 

  22. Jang HJ, Kokrashvili Z, Theodorakis MJ, et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide 1. Proc Natl Acad Sci U S A. 2007;104:15069–15074.

    Article  PubMed  CAS  Google Scholar 

  23. Kokrashvili Z, Mosinger B, Margolskee RF. Taste signaling elements expressed in gut enteroendocrine cells regulate nutrient-responsive secretion of gut hormones. Am J Clin Nutr. 2009;90:822S–825S.

    Article  PubMed  CAS  Google Scholar 

  24. Margolskee RF, Dyer J, Kokrashvili Z, et al. T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci U S A. 2007;104:15075–15080.

    Article  PubMed  CAS  Google Scholar 

  25. Chen M, Yang Y, Braunstein E, Georgeson KE, Harmon CM. Gut expression and regulation of FAT/CD36: possible role in fatty acid transport in rat enterocytes. Am J Physiol Endocrinol Metab. 2001;281:E916–E923.

    PubMed  CAS  Google Scholar 

  26. Lin L, Chen J, York DA. Chronic ICV enterostatin preferentially reduced fat intake and lowered body weight. Peptides. 1997;18:657–661.

    Article  PubMed  CAS  Google Scholar 

  27. Primeaux SD. QRFP in female rats: effects on high fat food intake and hypothalamic gene expression across the estrous cycle. Peptides. 2011;32:1270–1275.

    Article  PubMed  CAS  Google Scholar 

  28. Primeaux SD, York DA, Bray GA. Neuropeptide Y administration into the amygdala alters high fat food intake. Peptides. 2006;27:1644–1651.

    Article  PubMed  CAS  Google Scholar 

  29. Primeaux SD, Blackmon C, Barnes MJ, Braymer HD, Bray GA. Central administration of the RF amide peptides, QRFP-26 and QRFP-43, increases high fat food intake in rats. Peptides. 2008;29:1994–2000.

    Article  PubMed  CAS  Google Scholar 

  30. Lin L, Martin RJ, Schaffhauser AO, York DA. Acute changes in the response to peripheral leptin with alteration in the diet composition. Am J Physiol Regulat Integrat Comp Physiol. 2001;280:R504–R509.

    CAS  Google Scholar 

  31. Lin L, York DA. Comparisons of the effects of enterostatin on food intake and gastric emptying in rats. Brain Res. 1997;745:205–209.

    Article  PubMed  CAS  Google Scholar 

  32. Madiehe AM, Schaffhauser AO, Braymer DH, Bray GA, York DA. Differential expression of leptin receptor in high- and low-fat-fed Osborne-Mendel and S5B/Pl rats. Obes Res. 2000;8:467–474.

    Article  PubMed  CAS  Google Scholar 

  33. Okada S, York DA, Bray GA, Mei J, Erlanson-Albertsson C. Differential inhibition of fat intake in two strains of rat by the peptide enterostatin. Am J Physiol. 1992;262:R1111–R1116.

    PubMed  CAS  Google Scholar 

  34. Ookuma K, Barton C, York DA, Bray GA. Differential response to kappa-opioidergic agents in dietary fat selection between Osborne-Mendel and S5B/P1 rats. Peptides. 1998;19:141–147.

    Article  PubMed  CAS  Google Scholar 

  35. Schaffhauser AO, Madiehe AM, Braymer HD, Bray GA, York DA. Effects of a high-fat diet and strain on hypothalamic gene expression in rats. Obes Res. 2002;10:1188–1196.

    Article  PubMed  CAS  Google Scholar 

  36. Schemmel RA, Teague RJ, Bray GA. Obesity in Osborne-Mendel and S5B/Pl rats: effects of sucrose solutions, castration, and treatment with estadiol or insulin. Am J Physiol. 1982;243:R347–R353.

    PubMed  CAS  Google Scholar 

  37. Thanos PK, Cho J, Kim R, et al. Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats. Behav Brain Res. 2011;217:165–170.

    Article  PubMed  CAS  Google Scholar 

  38. Thanos PK, Kim R, Cho J, et al. Obesity-resistant S5B rats showed greater cocaine conditioned place preference than the obesity-prone OM rat. Physiol Behav. 2010;101:713–718.

    Article  PubMed  CAS  Google Scholar 

  39. White CL, Ishii Y, Mendoza T, et al. Effect of a selective OX1R antagonist on food intake and body weight in two strains of rats that differ in susceptibility to dietary-induced obesity. Peptides. 2005;26:2331–2338.

    Article  PubMed  CAS  Google Scholar 

  40. Gilbertson TA, Liu L, Kim I, Burks KA, Hansen DR. Fatty acid responses in taste cells from obesity-prone and -resistant rats. Physiol Behav. 2005;86:681–690.

    Article  PubMed  CAS  Google Scholar 

  41. El-Yassimi A, Hichami A, Besnard P, Khan NA. Linoleic acid induces calcium signaling, Src kinase phosphorylation and neurotransmitter release in mouse CD36-positive gustatory cells. J Biol Chem. 2008;283:12949–12959.

    Article  PubMed  CAS  Google Scholar 

  42. Gaillard D, Passilly-Degrace P, Besnard P. Molecular mechanisms of fat preference and overeating. Ann N Y Acad Sci. 2008;1141:163–175.

    Article  PubMed  CAS  Google Scholar 

  43. Khan NA, Besnard P. Oro-sensory preception of dietary lipids: new insights into the fat taste transduction. Biochim Biophys Acta. 2009;1791:149–155.

    Article  PubMed  CAS  Google Scholar 

  44. Martin C, Passilly-Degrace P, Merlin JF, Chevrot M, Besnard P. The lipid-sensor candidates CD36 and GPR120 are differentially regulated by dietary lipids in mouse taste buds: impact on spontaneous fat preference. PLoS ONE. 2011;6:e24014.

    Article  PubMed  CAS  Google Scholar 

  45. Mizushige T, Inoue K, Fushiki T. Why is fat so tasty? Chemical reception of fatty acid on tongue. J Nutr Sci Vitaminol (Tokyo). 2007;53:1–4.

    Article  CAS  Google Scholar 

  46. Passilly-Degrace P, Gaillard D, Besnard P. Orosensory perception of dietary lipids in mammals. Results Probl Cell Differ. 2009;47:221–238.

    PubMed  CAS  Google Scholar 

  47. Simons PJ, Boon L. Lingual CD36 and obesity: a matter of fat taste? Acta Histochem. 2011;113:765–767.

    Article  PubMed  Google Scholar 

  48. Simons PJ, Kummer JA, Luiken JJ, Boon L. Apical CD36 immunolocalization in human and procine taste buds from circumvallate and foliate papillae. Acta Histochem. 2011;113:839–843.

    Article  PubMed  CAS  Google Scholar 

  49. Zhang XJ, Zhou LH, Ban X, Liu DX, Jiang W, Liu XM. Decreased expression of CD36 in circumvallate taste buds of high-fat induced obese rats. Acta Histochem. 2011;113:663–667.

    Article  PubMed  CAS  Google Scholar 

  50. Guijarro A, Fu J, Astarita G, Piomelli D. CD36 gene deletion decreases oleoylethanolamide levels in small intestine of free-feeding mice. Pharmacol Res. 2010;61:27–33.

    Article  PubMed  CAS  Google Scholar 

  51. Schwartz GJ, Fu J, Astarita G, et al. The lipid messenger OEA links dietary fat intake to satiety. Cell Metab. 2008;8:281–288.

    Article  PubMed  CAS  Google Scholar 

  52. Yang Y, Chen M, Loux TJ, Harmon CM. Regulation of FAT/CD36 mRNA gene expression by long chain fatty acids in the differentiated 3T3-L1 cells. Pediatr Surg Int. 2007;23:675–683.

    Article  PubMed  Google Scholar 

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Acknowledgments

This research was supported by NIDDK 32089 to G.A. Bray. The authors would like to thank Christine Blackmon, Katherine Pyburn, and Daniel Shaheen for their assistance on this project. This work was supported in part by P20-RR021945 from the National Center for Research Resources and NIH Center Grant 1P30 DK072476.

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Correspondence to Stefany D. Primeaux.

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Primeaux, S.D., Braymer, H.D. & Bray, G.A. CD36 mRNA in the Gastrointestinal Tract Is Differentially Regulated by Dietary Fat Intake in Obesity-Prone and Obesity-Resistant Rats. Dig Dis Sci 58, 363–370 (2013). https://doi.org/10.1007/s10620-012-2364-4

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  • DOI: https://doi.org/10.1007/s10620-012-2364-4

Keywords

  • Obesity-prone
  • Obesity-resistant
  • CD36
  • Taste bud
  • Duodenum
  • High-fat diet