Display options
Share it on

J Nutr Biochem. 2021 Dec;98:108819. doi: 10.1016/j.jnutbio.2021.108819. Epub 2021 Jul 13.

Uncoupling protein 1-independent effects of eicosapentaenoic acid in brown adipose tissue of diet-induced obese female mice.

The Journal of nutritional biochemistry

Emily K Miller, Mandana Pahlavani, Latha Ramalingam, Shane Scoggin, Naima Moustaid-Moussa

Affiliations

  1. Department of Nutritional Sciences, and Obesity Research Institute, Texas Tech University, Lubbock, Texas.
  2. Department of Nutritional Sciences, and Obesity Research Institute, Texas Tech University, Lubbock, Texas; Department of Nutrition and Food Studies, Syracuse University, Syracuse, New York ,13210.
  3. Department of Nutritional Sciences, and Obesity Research Institute, Texas Tech University, Lubbock, Texas. Electronic address: [email protected].

PMID: 34271101 PMCID: PMC8571038 DOI: 10.1016/j.jnutbio.2021.108819

Abstract

Brown adipose tissue (BAT) plays a key role in energy expenditure through its thermogenic function, making its activation a popular target to reduce obesity. We recently reported that male mice housed at thermoneutrality with uncoupling protein 1 (UCP1) deficiency had increased weight gain and glucose intolerance, but eicosapentaenoic acid (EPA) ameliorated these effects. Whether female mice respond similarly to lack of UCP1 and to EPA remains unknown. We hypothesize that the effects of EPA on BAT activation are independent of UCP1 expression. We used female wild type (WT) and UCP1 knockout (KO) mice housed at thermoneutrality (30°C) as an obesogenic environment and fed them high fat (HF) diets with or without EPA for up to 14 weeks. Body weight (BW), body composition, and insulin and glucose tolerance tests were performed during the feeding trial. At termination, serum and BAT were harvested for further analyses. Mice in the KO-EPA group had significantly lower BW than KO-HF mice. In addition, KO-HF mice displayed significantly impaired glucose tolerance compared to their WT-HF littermates. However, EPA significantly enhanced glucose clearance in the KO mice compared to KO-HF mice. Protein levels of the mitochondrial cytochrome C oxidase subunits I, II, and IV were significantly lower in KO mice compared to WT. Our findings support that ablation of UCP1 is detrimental to energy metabolism of female mice in thermoneutral conditions. However, unexpectedly, EPA's protective effects against diet-induced obesity and glucose intolerance in these mice were independent of UCP1.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: Brown adipose tissue; Eicosapentaenoic acid; Female mice; Obesity; Thermoneutrality; Uncoupling protein 1

References

  1. Lipids Health Dis. 2017 Jul 3;16(1):131 - PubMed
  2. Am J Public Health. 2013 Oct;103(10):1895-901 - PubMed
  3. FASEB J. 2009 Jun;23(6):1946-57 - PubMed
  4. Food Funct. 2017 Apr 19;8(4):1481-1493 - PubMed
  5. Prog Lipid Res. 2011 Oct;50(4):372-87 - PubMed
  6. Am J Physiol Endocrinol Metab. 2013 Jun 15;304(12):E1391-403 - PubMed
  7. Cell Physiol Biochem. 2007;19(1-4):195-204 - PubMed
  8. Diabetes Care. 2015 Aug;38(8):1567-82 - PubMed
  9. Heart Metab. 2016 Mar;69:9-14 - PubMed
  10. J Pharmacokinet Pharmacodyn. 2014 Dec;41(6):655-73 - PubMed
  11. Mol Nutr Food Res. 2019 Apr;63(7):e1800821 - PubMed
  12. Diabetes. 2015 Jul;64(7):2352-60 - PubMed
  13. Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):7981-7986 - PubMed
  14. Sci Rep. 2015 Dec 17;5:18013 - PubMed
  15. Physiol Res. 2013;62(2):153-61 - PubMed
  16. Prostaglandins Leukot Essent Fatty Acids. 2018 Sep;136:47-55 - PubMed
  17. Cell Metab. 2009 Feb;9(2):203-9 - PubMed
  18. J Biol Chem. 2007 Apr 20;282(16):12240-8 - PubMed
  19. Eur J Nutr. 2016 Feb;55(1):159-69 - PubMed
  20. Nat Med. 2017 Dec;23(12):1454-1465 - PubMed
  21. Cell Metab. 2016 Apr 12;23(4):602-9 - PubMed
  22. J Nutr. 2010 Nov;140(11):1915-22 - PubMed
  23. Semin Immunopathol. 2019 Nov;41(6):757-766 - PubMed
  24. Am J Physiol Regul Integr Comp Physiol. 2017 Jan 1;312(1):R74-R84 - PubMed
  25. Am J Clin Nutr. 1997 May;65(5 Suppl):1645S-1654S - PubMed
  26. Pflugers Arch. 2016 Sep;468(9):1527-40 - PubMed
  27. Eur Rev Med Pharmacol Sci. 2015;19(3):441-5 - PubMed
  28. Am J Physiol. 1986 Nov;251(5 Pt 1):E576-83 - PubMed
  29. J Clin Invest. 2013 Jan;123(1):215-23 - PubMed
  30. Cell Rep. 2013 Dec 12;5(5):1196-203 - PubMed
  31. Dtsch Arztebl Int. 2014 Oct 17;111(42):705-13 - PubMed
  32. J Lipid Res. 2016 Aug;57(8):1382-97 - PubMed
  33. Am J Clin Nutr. 1997 Sep;66(3):649-59 - PubMed
  34. PLoS One. 2011 Mar 02;6(3):e17504 - PubMed
  35. J Nutr Biochem. 2017 Jan;39:101-109 - PubMed
  36. Obesity (Silver Spring). 2010 Mar;18(3):463-9 - PubMed
  37. Cell. 2012 Oct 12;151(2):400-13 - PubMed
  38. Cell. 2015 Oct 22;163(3):643-55 - PubMed
  39. Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E444-52 - PubMed
  40. Diabetes. 2009 Apr;58(4):803-12 - PubMed
  41. Int J Obes (Lond). 2015 Oct;39(10):1539-47 - PubMed
  42. P T. 2013 Nov;38(11):681-91 - PubMed
  43. Prev Nutr Food Sci. 2017 Dec;22(4):251-262 - PubMed
  44. Lancet. 1989 Sep 30;2(8666):757-61 - PubMed
  45. Mol Metab. 2018 Jan;7:161-170 - PubMed
  46. EMBO Rep. 2016 Mar;17(3):383-99 - PubMed
  47. Am J Physiol Endocrinol Metab. 2020 Nov 1;319(5):E944-E946 - PubMed
  48. J Nutr. 2015 Mar;145(3):411-7 - PubMed
  49. Channels (Austin). 2017 Mar 4;11(2):94-96 - PubMed
  50. NCHS Data Brief. 2017 Oct;(288):1-8 - PubMed
  51. Prog Biophys Mol Biol. 2006 Jan-Apr;90(1-3):299-325 - PubMed
  52. Int J Mol Med. 2009 Jul;24(1):125-9 - PubMed
  53. J Clin Invest. 2003 Feb;111(3):399-407 - PubMed

Publication Types

Grant support