Capsaicin supplementation prevents western diet-induced hyperleptinemia by reducing endoplasmic reticulum stress in apolipoprotein E-deficient mice

  • Hyun Ju Kim Kimchi Functionality Research Group, World Institute of Kimchi, Nam-Gu, Gwangju, South Korea
Keywords: endoplasmic reticulum stress, capsaicin, Western diet, hyperleptinemia, apolipoprotein E-deficient mice

Abstract

Background: Endoplasmic reticulum (ER) stress implicated in leptin resistance in the diet-induced obesity, which can accelerate the development of atherosclerosis forms the background of this study.

Objective: This study aimed to investigate the effect of capsaicin on hyperleptinema by inhibiting ER stress in apolipoprotein E-deficient (ApoE-/-) mice fed a western diet (WD).

Design: ApoE -/- mice were assigned one of three experimental diets: WD (60% kcal from fat, n = 10), WD + 0.015% capsaicin (n = 10, w/w), and WD + 1% PBA (n = 10, w/w) for 12 weeks.

Results: In metabolic parameters, supplementation of dietary capsaicin displayed marked reduction of body weight gain and adipose tissue weight, plasma leptin, total cholesterol, and hepatic triglyceride levels without change in the plasma insulin level compared with WD fed ApoE-/- mice after 12 weeks. Capsaicin supplementation also attenuated the protein expression of ER stress markers such as eukaryotic translational initiation factor 2α and C/EBP homology protein in the liver, as well as glucose-related protein 78 localization in the aorta, indicating that capsaicin inhibits diet-induced hyperleptinemia in part by regulating the protein expression involved in ER stress.

Conclusion: Capsaicin, therefore, may have potential as a therapeutic agent for individuals with diet-induced hyperleptinemia

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References


1.
Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011; 473: 317–25. doi: 10.1038/nature10146

2.
Lusis AJ, Mar R, Pajukanta P. Genetics of atherosclerosis. Annu Rev Genomics Hum Genet 2004; 5: 189–218. doi: 10.1146/annurev.genom.5.061903.175930

3.
Zhou J, Lhoták Š, Hilditch BA, Austin RC. Activation of the unfolded protein response occurs at all stages of atherosclerotic lesion development in apolipoprotein E-deficient mice. Circulation 2005; 111: 1814–21. doi: 10.1161/01.CIR.0000160864.31351.C1

4.
Xu C, Bailly-Maitre B, Reed JC. Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 2005; 115: 2656–64. doi: 10.1172/JCI26373

5.
Dickhout JG, Hossain GS, Pozza LM, Zhou J, Lhotak S, Austin RC. Peroxynitrite causes endoplasmic reticulum stress and apoptosis in human vascular endothelium: implications in atherogenesis. Arterioscler Thromb Vasc Biol 2005; 25: 2623–9. doi: 10.1161/01.ATV.0000189159.96900.d9

6.
Kim HJ, Sung YB, Song YO, Kang M, Kim TW, Park SH, et al. Kimchi suppresses 7-ketocholesterol-induced endoplasmic reticulum stress in macrophages. Food Sci Biotechnol 2012; 21: 1293–9. doi: 10.1007/s10068-012-0170-6

7.
Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science 2011; 334: 1081–6. doi: 10.1126/science.1209038

8.
Sanson M, Augé N, Vindis C, Muller C, Bando Y, Thiers JC, et al. Oxidized low-density lipoproteins triggers endoplasmic reticulum stress in vascular cells: prevention by oxygen-regulated protein 150 expression. Circ Res 2009; 104: 328–36. doi: 10.1161/CIRCRESAHA.108.183749

9.
Tapsell LC, Hemphill I, Cobiac L, Patch CS, Sullivan DR, Fenech M, et al. Health benefits of herbs and spices: the past, the present, the future. Med J Aust 2006; 185: S1–24. doi: 10.5694/j.1326-5377.2006.tb00548.x

10.
Sun F, Xiong S, Zhu Z. Dietary capsaicin protects cardiometabolic organs from dysfunction. Nutrients 2016; 8: 174–86. doi: 10.3390/nu8050174

11.
Qin Y, Ran L, Wang J, Yu L, Lang HD, Wang XL, et al. Capsaicin supplementation improved risk factors of coronary heart disease in individuals with low HDL-C levels. Nutrients 2017; 9: 1037–49. doi: 10.3390/nu9091037

12.
Govindarajan VS, Sathyanarayana MN. Capsicum-production, technology, chemistry, and quality. Part. Impact on physiology, pharmacology, nutrition, and metabolism; structure, pungency, pain, and desensitization sequences. Crit Rev Food Sci Nutr 1991; 29: 435–74. doi: 10.1080/10408399109527536

13.
Özcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 2006; 313: 1137–40. doi: 10.1126/science.1128294

14.
Folch J, Lee M, Stanley GHS. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 226: 479–509. doi: 10.1016/S0021-9258(18)64849-5

15.
Kim HJ, Moradi H, Yuan J, Norris K, Vaziri ND. Renal mass reduction results in accumulation of lipids and dysregulation of lipid regulatory proteins in the remnant kidney. Am J Physiol Renal Physiol 2009; 296: F1297–306. doi: 10.1152/ajprenal.90761.2008

16.
Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763–70. doi: 10.1038/27376

17.
Friedman J. The long road to leptin. J Clin Invest 2016; 126: 4727–34. doi: 10.1172/JCI91578

18.
Ozcan L, Ergin AS, Lu A, Chung J, Sarkar S, Nie D, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab 2009; 9: 35–51. doi: 10.1016/j.cmet.2008.12.004

19.
Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamic IKKβ/NF-κB and ER stress link overnutrition to energy imbalance and obesity. Cell 2008; 135: 61–73. doi: 10.1016/j.cell.2008.07.043

20.
Won JC, Jang PG, Namkoong C, Koh EH, Kim SK, Park JY, et al. Central administration of an endoplasmic reticulum stress inducer inhibits the anorexigenic effects of leptin and insulin. Obesity 2009; 17: 1861–5. doi: 10.1038/oby.2009.194

21.
Kang JH, Tsuyoshi G, Han IS, Kawada T, Kim YM, Yu R. Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. Obesity 2010; 18: 780–7. doi: 10.1038/oby.2009.301

22.
Kida R, Noguchi T, Murakami M, Hashimoto O, Kawada T, Matsui T, et al. Supra-pharmacological concentration of capsaicin stimulates brown adipogenesis through induction of endoplasmic reticulum stress. Sci. Rep 2018; 8: 845–57. doi: 10.1038/s41598-018-19223-2

23.
Lee GR, Shin MK, Yoon DJ, Kim AR, Yu R, Park NH, et al. Topical application of capsaicin reduces visceral adipose fat by affecting adipokine levels in high fat diet-induced obese mice. Obesity 2013; 21: 115–22. doi: 10.1002/oby.20246

24.
Lee E, Jung DY, Kim JH, Patel PR, Hu X, Lee Y, et al. Transient receptor potential vanilloid type-1 channel regulates diet-induced obesity, insulin resistance, and leptin resistance. FASEB J 2015; 29: 3182–92. doi: 10.1096/fj.14-268300

25.
Min BK, Kang HJ, Choi BJ, Jeon YH, Cho JY, Lee IK, et al. Phenylbutyrate ameliorates high-fat diet-induced obesity via brown adipose tissue activation. Biol Pharm Bull 2019; 42: 1554–61. doi: 10.1248/bpb.b19-00346

26.
Saito M, Matsushita M, Yoneshiro T, Okamatsu-Ogura Y. Brown adipose tissue, diet-induced thermogenesis, and thermogenic food ingredients: from mice to men. Front Endocrinol 2020; 11: 222 doi: 10.3389/fendo.2020.00222

27.
Bousquet J, Cristol J, Czarlewski W, Anto JM, Martineau A, Haahtela T, et al. Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies. Clin Transl Allergy 2020; 10: 58–77. doi: 10.1186/s13601-020-00362-7

28.
Hui S, Huang L, Wang X, Zhu X, Zhou M, Chen M, et al. Capsaicin improves glucose homeostasis by enhancing glucagon-like peptide-1 secretion through the regulation of bile acid metabolism via the remodeling of the gut microbiota in male mice. FASEB J 2020; 34: 8558–73. doi: 10.1096/fj.201902618RR

29.
Ferdowsi PV, Ahuja KDK, Beckett JM, Myers S. TRPV1 activation by capsaicin mediates glucose oxidation and ATP production independent of insulin signaling in mouse skeletal muscle cells. Cells 2021; 10: 1560 doi: 10.3390/cells10061560

30.
Zeng H, Shi N, Peng W, Yang Q, Ren J, Yang H, et al. Effects of capsaicin on glucose uptake and consumption in hepatocytes. Molecules 2023; 28: 5258 doi: 10.3390/molecules28135258

31.
Zhang S, Tang L, Xu F, Hui Y, Lu H, Liu X. TRPV1 receptor-mediated hypoglycemic mechanism of capsaicin in streptozotocin-induced diabetic rats. Front Nutr 2021; 8: 750355 doi: 10.3389/fnut.2021.750355

32.
Foshati S, Moradi S, Tavassoly M, Rouhani MH. Short- and long-term effects of capsaicin supplementation on glycemic control: a systematic review and meta-analysis of controlled trials. Food Funct 2021; 12: 5236–46. doi: 10.1039/D1FO00595B

33.
Harding HP, Zhang Y, Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 1999; 397: 271–4. doi: 10.1038/16729

34.
Han J, Kaufman RJ. The role of ER stress in lipid metabolism and lipotoxicity. J Lipid Res 2016; 57: 1329–38. doi: 10.1194/jlr.R067595

35.
Sozen E, Ozer NK. Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: an updated mini-review. Redox Biol 2017; 12: 456–61. doi: 10.1016/j.redox.2017.02.025

36.
Lee AH, Scapa EF, Cohen DE, Glimcher LH. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 2008; 320: 1492–6. doi: 10.1126/science.1158042

37.
Tsukano H, Gotoh T, Endo M, Miyata K, Tazume H, Kadomatsu T, et al. The endoplasmic reticulum stress-C/EBP homologous protein pathway-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2010; 30: 1925–32. doi: 10.1161/ATVBAHA.110.206094

38.
Oyadomari S, Harding HP, Zhang Y, Oyadomari M, Ron D. Dephosphorylation of translation initiation factor 2 alpha enhances glucose tolerance and attenuates hepatosteatosis in mice. Cell Metab 2008; 7: 520–32. doi: 10.1016/j.cmet.2008.04.011

39.
Girona J, Rodriguez-Borjabad C, Ibarretxe D, Vallve JC, Ferre R, Heras M, et al. The circulating GRP78/Bip is a marker of metabolic diseases and atherosclerosis: bringing endoplasmic reticulum stress into the clinical scenario. J Clin Med 2019; 8: 1793 doi: 10.3390/jcm8111793

40.
Kammoun HL, Chabanon H, Hainault I, Luquet S, Magnan C, Koike T, et al. GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice. J Clin Invest 2009; 119: 1201–15. doi: 10.1172/JCI37007
Published
2023-12-06
How to Cite
Kim H. J. (2023). Capsaicin supplementation prevents western diet-induced hyperleptinemia by reducing endoplasmic reticulum stress in apolipoprotein E-deficient mice. Food & Nutrition Research, 67. https://doi.org/10.29219/fnr.v67.9610
Section
Original Articles