Skip to main content
SpringerLink
Log in

Walnut supplementation increases levels of UCP1 and CD36 in brown adipose tissue independently of diet type

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Dietary interventions that modulate the brown adipose tissue (BAT) thermogenic activity could represent a promising therapy for metabolic disorders. In order to examine if dietary walnuts intake regulates the expression of BAT thermogenic markers levels in healthy and metabolically challenged (fructose fed) animals, rats were initially divided into the control and fructose-fed groups. After nine weeks, these groups were subdivided into the one kept on the original regimens and the other supplemented with walnuts. High-fructose diet resulted in an increased relative BAT mass and no change in UCP1 content, while the walnut supplementation increased the amount of UCP1 in BAT, but did not affect 5-HT, NA, DHPG content and DHPG/NA ratio regardless of the diet. Moreover, the CD36 levels were increased following the walnut consumption, unlike FATP1, GLUT1, GLUT4, and glycogen content which remained unchanged. Additionally, the BAT levels of activated IR and Akt were not affected by walnut consumption, while ERK signaling was decreased. Overall, we found that walnut consumption increased UCP1 and CD36 content in the BAT of both control and metabolically challenged rats, suggesting that FFAs represent the BAT preferred substrate under the previously described circumstances. This further implies that incorporating walnuts into the everyday diet may help to alleviate some symptoms of the metabolic disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

No datasets were generated or analysed during the current study.

References

  1. Bargut TCL, Silva-e-Silva ACAG, Souza-Mello V, Mandarim-de-Lacerda CA, Aguila MB (2016) Mice fed fish oil diet and upregulation of brown adipose tissue thermogenic markers. Eur J Nutr 55. https://doi.org/10.1007/s00394-015-0834-0

  2. Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Weller H, Waurisch C, Eychmüller A, Gordts PLSM, Rinninger F, Bruegelmann K, Freund B, Nielsen P, Merkel M, Heeren J (2011) Brown adipose tissue activity controls triglyceride clearance. Nat Med 17. https://doi.org/10.1038/nm.2297

    Article  Google Scholar 

  3. Betz MJ, Enerbäck S (2018) Targeting thermogenesis in brown fat and muscle to treat obesity and metabolic disease. Nat Rev Endocrinol 14:77–87. https://doi.org/10.1038/nrendo.2017.132

    Article  CAS  PubMed  Google Scholar 

  4. Bolling BW, McKay DL, Blumberg JB (2010) The phytochemical composition and antioxidant actions of tree nuts. Asia Pac J Clin Nutr 19:117–123. https://doi.org/10.6133/apjcn.2010.19.1.16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Brenna JT, Salem N, Sinclair AJ, Cunnane SC (2009) α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fat Acids 80. https://doi.org/10.1016/j.plefa.2009.01.004

  6. Calderon-Dominguez M, Mir JF, Fucho R, Weber M, Serra D, Herrero L (2016) Fatty acid metabolism and the basis of brown adipose tissue function. Adipocyte 5:98–118. https://doi.org/10.1080/21623945.2015.1122857

    Article  CAS  PubMed  Google Scholar 

  7. Castro-Barquero S, Ruiz-León AM, Sierra-Pérez M, Estruch R, Casas R (2020) Dietary strategies for metabolic syndrome: a comprehensive review. Nutrients 12:2983. https://doi.org/10.3390/nu12102983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chan AML, Ng AMH, Mohd Yunus MH, Idrus RBH, Law JX, Yazid MD, Chin KY, Shamsuddin SA, Lokanathan Y (2021) Recent developments in rodent models of high-fructose diet-induced metabolic syndrome: a systematic review. Nutrients 13:2497. https://doi.org/10.3390/nu13082497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng Y-H, Doria A, Kolodny GM, Kahn CR (2009) Identification and importance of Brown Adipose tissue in adult humans. N Engl J Med 360:1509–1517. https://doi.org/10.1056/nejmoa0810780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dong M, Lin J, Lim W, Jin W, Lee HJ (2018) Role of brown adipose tissue in metabolic syndrome, aging, and cancer cachexia. Front Med 12:130–138. https://doi.org/10.1007/s11684-017-0555-2

    Article  PubMed  Google Scholar 

  11. Farkas V, Kelenyi G, Sandor A (1999) A dramatic accumulation of glycogen in the brown adipose tissue of rats following recovery from cold exposure. Arch Biochem Biophys 365. https://doi.org/10.1006/abbi.1999.1157

  12. Fedorenko A, Lishko PV, Kirichok Y (2012) Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell 151:400–413. https://doi.org/10.1016/j.cell.2012.09.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Greenberg AS, Shen WJ, Muliro K, Patel S, Souza SC, Roth RA, Kraemer FB (2001) Stimulation of Lipolysis and hormone-sensitive lipase via the Extracellular Signal-regulated kinase pathway. J Biol Chem 276. https://doi.org/10.1074/jbc.m104436200

  14. Gunawan S, Aulia A, Soetikno V (2021) Development of rat metabolic syndrome models: a review. Vet World 14:1774–1783. https://doi.org/10.14202/vetworld.2021.1774-1783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J, Heldmaier G, Maier R, Theussl C, Eder S, Kratky D, Wagner EF, Klingenspor M, Hoefler G, Zechner R (2006) Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 312. https://doi.org/10.1126/science.1123965

  16. Hao Q, Yadav R, Basse AL, Petersen S, Sonne SB, Rasmussen S, Zhu Q, Lu Z, Wang J, Audouze K, Gupta R, Madsen L, Kristiansen K, Hansen JB (2015) Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism. Am J Physiol - Endocrinol Metab 308. https://doi.org/10.1152/ajpendo.00277. 2014

  17. Herz CT, Kulterer OC, Prager M, Schmöltzer C, Langer FB, Prager G, Marculescu R, Kautzky-Willer A, Hacker M, Haug AR, Kiefer FW (2022) Active brown adipose tissue is Associated with a healthier metabolic phenotype in obesity. Diabetes 71. https://doi.org/10.2337/db21-0475

  18. Huber KR, Wödl H, Robubi A, Hauser A, Schrattbauer K, Krugluger W (2016) In Vitro Culture of Human Brown adipocytes: effects of Fructose. Int J Life Sci Med Res 6:1–8. https://doi.org/10.5963/LSMR0601001

    Article  Google Scholar 

  19. Hwang HJ, Liu Y, Kim HS, Lee H, Lim Y, Park H (2019) Daily walnut intake improves metabolic syndrome status and increases circulating adiponectin levels: Randomized controlled crossover trial. Nutr Res Pract 13. https://doi.org/10.4162/nrp.2019.13.2.105

  20. Jakus PB, Sandor A, Janaky T, Farkas V (2008) Cooperation between BAT and WAT of rats in thermogenesis in response to cold, and the mechanism of glycogen accumulation in BAT during reacclimation. J Lipid Res 49. https://doi.org/10.1194/jlr.m700316-jlr200

  21. Jatkar A, Kurland IJ, Judex S (2017) Diets high in Fat or Fructose differentially modulate bone health and lipid metabolism. Calcif Tissue Int 100. https://doi.org/10.1007/s00223-016-0205-8

  22. Jung SM, Doxsey WG, Le J, Haley JA, Mazuecos L, Luciano AK, Li H, Jang C, Guertin DA (2021) In vivo isotope tracing reveals the versatility of glucose as a brown adipose tissue substrate. Cell Rep 36:109459. https://doi.org/10.1016/j.celrep.2021.109459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kawada T, Kayahashi S, Hida Y, Koga KJ, Nadachi Y, Fushiki T (1998) Fish (Bonito) Oil Supplementation enhances the expression of uncoupling protein in Brown Adipose tissue of rat. J Agric Food Chem 46. https://doi.org/10.1021/jf9711000

  24. Khedoe PPSJ, Hoeke G, Kooijman S, Dijk W, Buijs JT, Kersten S, Havekes LM, Hiemstra PS, Berbée JFP, Boon MR, Rensen PCN (2015) Brown adipose tissue takes up plasma triglycerides mostly after lipolysis. J Lipid Res 56. https://doi.org/10.1194/jlr.m052746

  25. Khitan Z, Kim DH (2013) Fructose: a key factor in the development of metabolic syndrome and hypertension. J Nutr Metab 2013:1–12. https://doi.org/10.1155/2013/682673

    Article  CAS  Google Scholar 

  26. Kim SH, Plutzky J (2016) Brown fat and browning for the treatment of obesity and related metabolic disorders. Diabetes Metab J 40:12–21. https://doi.org/10.4093/dmj.2016.40.1.12

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kim M, Goto T, Yu R, Uchida K, Tominaga M, Kano Y, Takahashi N, Kawada T (2015) Fish oil intake induces UCP1 upregulation in brown and white adipose tissue via the sympathetic nervous system. Sci Rep 5. https://doi.org/10.1038/srep18013

  28. Kuipers EN, Held NM, Panhuis W (2019) in het, Modder M, Ruppert PMM, Kersten S, Kooijman S, Guigas B, Houtkooper RH, Rensen PCN, Boon MR A single day of high-fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice. Am J Physiol - Endocrinol Metab 317. https://doi.org/10.1152/ajpendo.00123.2019

  29. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin-Phenol Reagent. J Biol Cemistry 193:265–275. https://doi.org/10.1016/S0021-9258(19)52451-6

    Article  CAS  Google Scholar 

  30. Maguire LS, O’Sullivan SM, Galvin K, O’Connor TP, O’Brien NM (2004) Fatty acid profile, tocopherol, squalene and phytosterol content of walnuts, almonds, peanuts, hazelnuts and the macadamia nut. Int J Food Sci Nutr 55:171–178. https://doi.org/10.1080/09637480410001725175

    Article  CAS  PubMed  Google Scholar 

  31. McNeill BT, Morton NM, Stimson RH (2020) Substrate utilization by Brown Adipose tissue: what’s Hot and what’s not? Front Endocrinol 11:1–8. https://doi.org/10.3389/fendo.2020.571659

    Article  Google Scholar 

  32. Oudart H, Groscolas R, Calgari C, Nibbelink M, Leray C, Le Maho Y, Malan A (1997) Brown fat thermogenesis in rats fed high-fat diets enriched with n-3 polyunsaturated fatty acids. Int J Obes 21. https://doi.org/10.1038/sj.ijo.0800500

  33. Ouellet V, Labbé SM, Blondin DP, Phoenix S, Guérin B, Haman F, Turcotte EE, Richard D, Carpentier AC (2012) Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest 122. https://doi.org/10.117 2/jci60433

  34. Pandareesh MD, Chauhan V, Chauhan A (2018) Walnut Supplementation in the Diet reduces oxidative damage and improves antioxidant status in transgenic mouse model of Alzheimer’s Disease. J Alzheimers Dis JAD 64:1295–1305. https://doi.org/10.3233/jad-180361

    Article  CAS  PubMed  Google Scholar 

  35. Petrović-Oggiano G, Debeljak-Martačić J, Ranković S, Pokimica B, Mirić A, Glibetić M, Popović T (2020) The effect of walnut consumption on n-3 fatty acid profile of healthy people living in a non-mediterranean west balkan country, a small scale randomized study. Nutrients 12:192. https://doi.org/10.3390/nu12010192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Postic C, Leturque A, Printz RL, Maulard P, Loizeau M, Granner DK, Girard J (1994) Development and regulation of glucose transporter and hexokinase expression in rat. Am J Physiol - Endocrinol Metab 266:E548–E559. https://doi.org/10.1152/ajpendo.1994.266.4.e548

    Article  CAS  Google Scholar 

  37. Putri M, Syamsunarno MRAA, Iso T, Yamaguchi A, Hanaoka H, Sunaga H, Koitabashi N, Matsui H, Yamazaki C, Kameo S, Tsushima Y, Yokoyama T, Koyama H, Abumrad NA, Kurabayashi M (2015) CD36 is indispensable for thermogenesis under conditions of fasting and cold stress. Biochem Biophys Res Commun 457. https://doi.org/10.1016/j.bbrc.201412.124

  38. Rasouli M, Ostovar-Ravari A, Shokri-Afra H (2014) Characterization and improvement of phenol-sulfuric acid microassay for glucose-based glycogen. Eur Rev Med Pharmacol Sci 18:2020–2024

    CAS  PubMed  Google Scholar 

  39. Rasouli M, Shokri-Afra H, Ostovar-Ravari A (2015) A new protocol for separation of acid soluble and insoluble fractions from total glycogen and simultaneous measurements. Eur Rev Med Pharmacol Sci 19:1785–1789

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  41. Richard G, Blondin DP, Syed SA, Rossi L, Fontes ME, Fortin M, Phoenix S, Frisch F, Dubreuil S, Guérin B, Turcotte ÉE, Lepage M, Surette MG, Schertzer JD, Steinberg GR, Morrison KM, Carpentier AC (2022) High-fructose feeding suppresses cold-stimulated brown adipose tissue glucose uptake independently of changes in thermogenesis and the gut microbiome. Cell Rep Med 3:100742. https://doi.org/10.1016/j.xcrm.2022.100742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Roberts-Toler C, O’Neill BT, Cypess AM (2015) Diet-induced obesity causes insulin resistance in mouse brown adipose tissue. https://doi.org/10.1002/oby.21134. Obesity 23

  43. Ros E, Br (2015) J Nutr 113:S111–S120. https://doi.org/10.1017/s0007114514003924

    Article  CAS  Google Scholar 

  44. Rothwell NJ, Stock MJ (1979) A role for brown adipose tissue in diet-induced thermogenesis. Nature 281. https://doi.org/10.1038/281031a0

  45. Saito M, Matsushita M, Yoneshiro T, Okamatsu-Ogura Y (2020) Brown Adipose tissue, Diet-Induced thermogenesis, and thermogenic food ingredients: from mice to men. Front Endocrinol 11:222. https://doi.org/10.3389/fendo.2020.00222

    Article  Google Scholar 

  46. Shin H, Ma Y, Chanturiya T, Cao Q, Wang Y, Kadegowda AKG, Jackson R, Rumore D, Xue B, Shi H, Gavrilova O, Yu L (2017) Lipolysis in Brown adipocytes is not essential for Cold-Induced thermogenesis in mice. Cell Metab 26. https://doi.org/10.1016/j.cmet.2017.09.002

  47. Stanford KI, Middelbeek RJW, Townsend KL, An D, Nygaard EB, Hitchcox KM, Markan KR, Nakano K, Hirshman MF, Tseng YH, Goodyear LJ (2013) Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest 123. https://doi.org/10.1172/jci62308

  48. Stanisic J, Ivkovic T, Romic S, Zec M, Culafic T, Stojiljkovic M, Koricanac G (2020) Beneficial effect of walnuts on vascular tone is associated with akt signalling, voltage-dependent calcium channel LTCC and ATP-sensitive potassium channel Kv1.2. Int J Food Sci Nutr 21:1–11. https://doi.org/10.1080/09637486.2020.1796931

    Article  CAS  Google Scholar 

  49. Townsend K, Tseng Y-H (2014) Brown Fat fuel utilization and thermogenesis. Trends Endocrinol Metab 25:168–177. https://doi.org/10.1016/j.tem.2013.12.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wade G, McGahee A, Ntambi JM, Simcox J (2021) Lipid Transport in brown adipocyte thermogenesis. Front Physiol 12:787535. https://doi.org/10.3389/fphys.2021.787535

    Article  PubMed  PubMed Central  Google Scholar 

  51. Wilson JE (2003) Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol 206:2049–2057. https://doi.org/10.1242/jeb.00241

    Article  CAS  PubMed  Google Scholar 

  52. Wu Q, Kazantzis M, Doege H, Ortegon AM, Tsang B, Falcon A, Stahl A (2006) Fatty acid transport protein 1 is required for nonshivering thermogenesis in brown adipose tissue. Diabetes 55. https://doi.org/10.2337/db06-0749

    Article  Google Scholar 

  53. Zambón D, Sabaté J, Muñoz S, Campero B, Casals E, Merlos M, Laguna JC, Ros E (2000) Substituting walnuts for monounsaturated fat improves the serum lipid profile of hypercholesterolemic men and women. A randomized crossover trial. Ann Intern Med 132:538–546. https://doi.org/10.7326/0003-4819-132-7-200004040-00005

    Article  PubMed  Google Scholar 

  54. Zec MM, Krga I, Takić M, Debeljak-Martačić J, Korićanac G, Ranković S, Popović T, Pantelić M, Glibetic M (2020) Walnut Consumption induces tissue-specific Omega-6/Omega-3 decrease in high-fructose-Fed Wistar rats. ACS Omega 5:28136–28145. https://doi.org/10.1021/acsomega.0c03784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, under the contract numbers 451-03-65/2024-03/ 200178 and 451-03-66/2024-03/ 200178.

Author information

Authors and Affiliations

  1. Department for Comparative Physiology and Ecophysiology, Institute for Physiology and Biochemistry “Ivan Djaja”, Faculty of Biology, University of Belgrade, Belgrade, 11000, Serbia

    Tamara Dakic, Dusan Jeremic, Iva Lakic, Nebojsa Jasnic, Aleksandra Ruzicic, Predrag Vujovic & Tanja Jevdjovic

Authors
  1. Tamara Dakic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dusan Jeremic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Iva Lakic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nebojsa Jasnic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aleksandra Ruzicic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Predrag Vujovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tanja Jevdjovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TJ conceived and designed the study. Material preparation, analysis and data collection were performed by DJ and TD. NJ performed the HPLC analysis. TJ and TD interpreted the data. IL collected tissue and contributed to the interpretation of the results. DJ wrote the Methods and Results section, rest of the first manuscript draft was written by TD. TJ, IL, AR, and PV reviewed and edited the paper.

Corresponding author

Correspondence to Tanja Jevdjovic.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dakic, T., Jeremic, D., Lakic, I. et al. Walnut supplementation increases levels of UCP1 and CD36 in brown adipose tissue independently of diet type. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-04981-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11010-024-04981-7

Keywords

Search

Navigation