Effects of Deep Sea Water on Anti-Obesity Properties in Induction of Beige Adipocytes

Author(s): Samihah Z.M. Nani *, Abubakar Jaafar, Fadzilah A.A. Majid, Akbariah Mahdzir, Md. Nor Musa.

Journal Name: Current Chemical Biology

Volume 13 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Objective: Deep sea water (DSW) accumulates many scientific shreds of evidence in treating obesity. Previous studies indicated that it reduces white adipose tissue (WAT) and body weight. WAT is energy storage fat, while beige adipose tissue is energy supply fat. In this study, the effects of DSW in the induction of beige adipocytes from mouse adipose tissue-derived stromal vascular fraction (SVF) cells are determined.

Methods: Adipose tissue-derived SVF cells were isolated from mice and used for induction of beige adipocytes and treated with DSW at several concentrations.

Results: During the course of beige adipocytes differentiation, DSW treatment increased lipid accumulation and upregulated adipogenic genes markers expression such as peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein a (C/EBP-α), and fatty acid binding protein 4 (FABP4), and also upregulated thermogenic genes markers such as the uncoupling protein 1 (UCP-1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and cell deathinducing DFFA-like effector A (Cidea) in beige adipocytes.

Conclusion: DSW has the potential to promote browning of WAT and upregulates the thermogenic genes that are responsible for energy expenditure.

Keywords: Deep sea water, beige, browning, obesity, thermogenesis, anti-obesity.

Hwang HS, Kim HA, Lee SH, Yun JW. Anti-obesity and antidiabetic effects of deep sea water on ob/ob mice. Mar Biotechnol 2009; 11(4): 531-9.
Hwang HS, Kim SH, Yoo YG, et al. Inhibitory effect of deep-sea water on differentiation of 3T3-L1 adipocytes. Mar Biotechnol 2009; 11(2): 161-8.
Ha BG, Park JE, Shin EJ, Shon YH. Effects of balanced deep sea water on adipocyte hypertrophy and liver steatosis in high-fat diet-induced obese mice. Obes (Silver Spring) 2014; 22(7): 1669-78
Harms M, Seale P. Brown and beige fat: Development, function and therapeutic potential. Nat Med 2013; 19(10): 1252-63.
Lidell ME, Betz MJ, Enerbäck S. Brown adipose tissue and its therapeutic potential. J Intern Med 2014; 276(4): 364-77.
Sambeat A, Gulyaeva O, Dempersmier J, Sul HS. Epigenetic Regulation of the thermogenic adipose program. Trends Endocrinol Metab 2017; 28(1): 19-31.
Wang W, Seale P. Control of brown and beige fat development. Nat Rev Mol Cell Biol 2016; 17(11): 691-702.
Wu J, Boström P, Sparks LM, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012; 150(2): 366-76.
Wu J, Jun H, McDermott JR. Formation and activation of thermogenic fat. Trends Genet 2015; 31(5): 232-8.
Wrighton KH. Metabolism: Mitophagy turns beige adipocytes white. Nat Rev Mol Cell Biol 2016; 17(10): 607.
Lizcano F, Vargas D. Biology of beige adipocyte and possible therapy for type 2 diabetes and obesity. Int J Endocrinol 2016; 2016: 9542061.
Lavallard VJ, Meijer AJ, Codogno P, Gual P. Autophagy, signaling and obesity. Pharmacol Res 2012; 66(6): 513-25.
Giralt M, Villarroya F. White, brown, beige/brite: Different adipose cells for different functions? Endocrinology 2013; 154(9): 2992-3000.
Bartelt A, Heeren J. Adipose tissue browning and metabolic health. Nat Rev Endocrinol 2014; 10(1): 24-36.
Xiao XH, Qi XY, Di Wang Y, et al. Zinc alpha2 glycoprotein promotes browning in adipocytes. Biochem Biophys Res Commun 2018; 496(2): 287-93.
Leu SY, Tsai Y-C, Chen WC, Hsu CH, Lee YM, Cheng PY. Raspberry ketone induces brown-like adipocyte formation through suppression of autophagy in adipocytes and adipose tissue. J Nutr Biochem 2018; 56: 116-25.
Lone J, Yun JW. Honokiol exerts dual effects on browning and apoptosis of adipocytes. Pharmacol Rep 2017; 69(6): 1357-65.
Dewal RS, Stanford KI. Effects of exercise on brown and beige adipocytes. Biochim Biophys Acta - Mol Cell Biol Lipids 2018; 18: pii: S1388-981.
Varela CE, Rodriguez A, Romero-Valdovinos M, et al. Browning effects of (-)-epicatechin on adipocytes and white adipose tissue. Eur J Pharmacol 2017; 811: 48-59.
Zou T, Wang B, Yang Q, et al. Raspberry promotes brown and beige adipocyte development in mice fed high-fat diet through activation of AMP-activated protein kinase (AMPK) α1. J Nutr Biochem 2018; 55: 157-64.
Lone J, Yun JW. Monoterpene limonene induces brown fat-like phenotype in 3T3-L1 white adipocytes. Life Sci 2016; 153: 198-206.
Parray HA, Lone J, Park JP, Choi JW, Yun JW. Magnolol promotes thermogenesis and attenuates oxidative stress in 3T3-L1 adipocytes. Nutrition 2018; 50: 82-90.
Lone J, Choi JH, Kim SW, Yun JW. Curcumin induces brown fat-like phenotype in 3T3-L1 and primary white adipocytes. J Nutr Biochem 2016; 27: 193-202.
Rodriguez Lanzi C, Perdicaro DJ, Landa MS, et al. Grape pomace extract induced beige cells in white adipose tissue from rats and in 3T3-L1 adipocytes. J Nutr Biochem 2018; 56: 224-33.
Rodríguez A, Becerril S, Ezquerro S. MéndezGiménez L, Frühbeck G. Cross-talk between adipokines and myokines in fat browning. Acta Physiol (Oxf) 2017; 219(2): 362-81.
Ricquier D. Uncoupling protein 1 of brown adipocytes, the only uncoupler: A historical perspective. Front Endocrinol 2011; 2: 1-7.
Nedergaard J, Golozoubova V, Matthias A, Asadi A, Jacobsson A, Cannon B. UCP1: The only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. Biochim Biophys Acta - Bioenerg 2001; 1504(1): 82-106
Kozak LP, Anunciado-Koza R. UCP1: Its involvement and utility in obesity. Int J Obes 2008; 32(Suppl. 7): S32-8.
Fedorenko A, Lishko PV, Kirichok Y. Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell 2013; 151(2): 400-13.
Kolumam G, Tong R, Zavala-Solorio J, et al. Sustained brown fat stimulation and insulin sensitization by a humanized bispecific antibody agonist for fibroblast growth factor receptor 1/βklotho complex. EBioMedicine 2015; 2(7): 730-43.
Shao M, Ishibashi J, Hepler C, Vishvanath L, Seale P, Gupta RK. Zfp423 maintains white adipocyte identity through suppression of the beige cell thermogenic gene program. Cell Metab 2016; 23(6): 1167-84.
Vitali A, Murano I, Zingaretti MC, et al. The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes. J Lipid Res 2012; 53(4): 619-9.
Kusminski CM, Bickel PE, Scherer PE. Targeting adipose tissue in the treatment of obesity-associated diabetes. Nat Publ Gr 2016; 15(9): 639-60.
Dani C, Billon N. Adipocyte precursors: Developmental origins, self-renewal, and plasticity.In: Symonds M.E, Ed. Adipose tissue biology, 2012th ed. New York, NY: Springer New York, 2012; pp. 1-16
Ruiz-Ojeda F, Rupérez A, Gomez-Llorente C, Gil A, Aguilera C. Cell models and their application for studying adipogenic differentiation in relation to obesity: A review. Int J Mol Sci 2016; 17(7): 1040.
Moreno-navarrete JM, Fernández-real JM. Adipocyte differentiation.In: Symonds M.E, Ed. Adipose tissue biology, 2012th ed. New York, NY: Springer New York, 2012; pp. 17-39.
Sanchez-Gurmaches J, Guertin D.A. Adipocyte lineages: Tracing back the origins of fat. Biochim Biophys Acta - Mol Basis Dis 2014; 1842(3): 340-51
Meissburger B, Perdikari A, Moest H, Müller S, Geiger M, Wolfrum C. Regulation of adipogenesis by paracrine factors from adipose stromal-vascular fraction - a link to fat depot-specific differences. Biochim Biophys Acta 2016; 1861(9): 1121-31.
Aune UL, Ruiz L, Kajimura S. Isolation and differentiation of stromal vascular cells to beige/brite cells. J Vis Exp 2013; 73: 1-6.
Ha BG, Moon D-S, Kim HJ, Shon YH. Magnesium and calcium-enriched deep-sea water promotes mitochondrial biogenesis by AMPK-activated signals pathway in 3T3-L1 preadipocytes. Biomed Pharmacother 2016; 83: 477-84.
Ha BG, Park J-E, Cho H-J, Shon YH. Stimulatory effects of balanced deep sea water on mitochondrial biogenesis and function. PLoS One 2015; 10(6): e0129972.
Heaton JM. The distribution of brown adipose tissue in the human. J Anat 1972; 112(Pt 1): 35-9.
Elander L, Slawik M, Mussack T, et al. Evidence for two types of brown adipose tissue in humans. Nat Med 2013; 19(5): 631-4.
Seale P. Transcriptional regulatory circuits controlling brown fat development and activation. Diabetes 2015; 64(7): 2369-75.
Garcia RA, Roemmich JN, Claycombe KJ. Evaluation of markers of beige adipocytes in white adipose tissue of the mouse. Nutr Metab 2016; 13(1): 24.
Hondares E, Rosell M, Díaz-Delfín J, Olmos Y, Monsalve M, Iglesias R, et al. Peroxisome proliferator-activated receptor α (PPARα) induces PPARγ coactivator 1α (PGC-1α) gene expression and contributes to thermogenic activation of brown fat: Involvement of PRDM16. J Biol Chem 2011; 286(50): 43112-22.
Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 1998; 92(6): 829-39.
Kleiner S, Mepani RJ, Laznik D, Ye L, Chatterjee Bhowmick D, Spiegelman BM. Development of insulin resistance in mice lacking PGC-1 in adipose tissues. Proc Natl Acad Sci 2012; 109: 9635-40.
Boström P, Wu J, Korde A, et al. A PGC1a dependent myokine that derives browning of white fat and thermogenesis. Nature 2012; 481(7382): 463-8.
Harms MJ, Ishibashi J, Wang W, et al. Prdm16 is required for the maintenance of brown adipocyte identity and function in adult mice. Cell Metab 2014; 19(4): 593-604.
Schulz TJ, Kokkotou E, Huang TL, et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 2008; 454(7207): 1000-4.
Iida S, Chen W, Nakadai T, Ohkuma Y, Roeder GR. PRDM16 enhances nuclear receptor-dependent transcription of the brown fat-specific Ucp1 gene through interactions with Mediator subunit MED1. Genes Dev 2015; 29(3): 308-21.
Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, et al. Initiation of myoblast/brown fat switch through a PRDM16- C/EBP-b transcriptional complex. Nature 2009; 460(7259): 1154-8.
Seale P, Conroe HM, Estall J, et al. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest 2011; 121(1): 53-6.
Lin GG, Scott JG. PPAR agonists induce a white-tobrown fat conversion through stabilization of PRDM16 protein. Cell Metab 2012; 100(2): 130-4.
Sheu M-J, Chou P-Y, Lin W-H, et al. Deep sea water modulates blood pressure and exhibits hypolipidemic effects via the AMPK-ACC pathway: An in vivo study. Mar Drugs 2013; 11(6): 2183-202.
Mac Takahashi M, Huang P. Novel renewable natural resource of Deep Ocean Water (DOW) and their current and future practical applications. Kuroshio Sci 2012; 2000: 101-13.
Mohd Nani SZ, Majid FAA, Jaafar AB, Mahdzir A, Musa MN. Potential health benefits of deep sea water: A review. Evidence-based Complement Altern Med 2016; 2016(1): 1-18.
Li Y, Wang C, Zhu K, Feng RN, Sun CH. Effects of multivitamin and mineral supplementation on adiposity, energy expenditure and lipid profiles in obese Chinese women. Int J Obes 2010; 34(6): 1070-7.
Pérez-Gallardo L, Gómez M, Parra P, Sánchez J, Palou A, Serra F. Effect of calcium-enriched high-fat diet on calcium, magnesium and zinc retention in mice. Br J Nutr 2009; 101(10): 1463-6.
Ames BN, Atamna H, Killilea DW. Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging. Mol Aspects Med 2005; 26(4-5): 363-78.
Fujii H. Nuclear receptor PPARs and magnesium. Clin Calcium 2005; 15(11): 52-64.
Itoh K, Kawasaka T, Nakamura M. The effects of high oral magnesium supplementation on blood pressure, serum lipids and related variables in apparently healthy Japanese subjects. Br J Nutr 1997; 78(5): 737-50.
Musso CG. Magnesium metabolism in health and disease. Int Urol Nephrol 2009; 41(2): 357-62.
Sales CH, Pedrosa LDFC. Magnesium and diabetes mellitus: Their relation. Clin Nutr 2006; 25(4): 554-62.
Sales CH, Rodrigues A, Santos D, Esper D, Cintra C, Colli C. Magnesium-deficient high-fat diet: Effects on adiposity, lipid profile and insulin sensitivity in growing rats. Clin Nutr 2014; 33: 879-88.
Zheltova AA, Kharitonova MV, Iezhitsa IN, Spasov AA. Magnesium deficiency and oxidative stress: An update. Biomedicine 2016; 6(4): 20.
Sergeev IN, Song Q. High vitamin D and calcium intakes reduce diet-induced obesity in mice by increasing adipose tissue apoptosis. Mol Nutr Food Res 2014; 58(6): 1342-8.
Wright DC, Geiger PC, Han DH, Jones TE, Holloszy JO. Calcium induces increases in peroxisome proliferator-activated receptor?? coactivator-1?? and mitochondrial biogenesis by a pathway leading to p38 mitogen-activated protein kinase activation. J Biol Chem 2007; 282(26): 18793-9.
Zemel MB. Regulation of adiposity and obesity risk by dietary calcium: Mechanisms and implications. J Am Coll Nutr 2002; 21(2): 146S-51S.
Vergara EJS, Dela Cruz J, Kim CM, Hwang SG. Increased adipocyte differentiation may be mediated by extracellular calcium levels through effects on calreticulin and peroxisome proliferator activated receptor gamma expression in intramuscular stromal vascular cells isolated from Hanwoo beef cattle. Ital J Anim Sci 2016; 15(2): 256-63.
Sanchez-Gurmaches J, Hung C-M, Guertin DA. Emerging complexities in adipocyte origins and identity. Trends Cell Biol 2016; 26(5): 313-26.
Van Eenige R, Van der Stelt M, Rensen PCN, Kooijman S. Regulation of adipose tissue metabolism by the endocannabinoid system. Trends Endocrinol Metab 2018; 29(5): 326-37.
Goody D, Pfeifer A. MicroRNAs in brown and beige fat. Biochim Biophys Acta 2018; 18: pii: S1388- 1981
Chen Y, Pan R, Pfeifer A. Regulation of brown and beige fat by microRNAs. Pharmacol Ther 2017; 170: 1-7.
Loft A, Forss I, Mandrup S. Genome-wide insights into the development and function of thermogenic adipocytes. Trends Endocrinol Metab 2017; 28(2): 104-20.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [38 - 48]
Pages: 11
DOI: 10.2174/2212796812666180705143429
Price: $58

Article Metrics

PDF: 57