3T3-L1 지방전구세포의 지방분화에서 멜라토닌의 영향
Effect of Melatonin on Differentiating 3T3-L1 Preadipocytes
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Adipocytes are the main constituent of adipose tissue. Understanding the molecular basis of adipogenesis is pivotal to finding the therapeutic targets for treatment of obesity. Melatonin is associated with obesity and its mechanism is currently under intensive investigation. The objective of this study was to investigate the effect of melatonin on adipogenesis in differentiating preadipocytes. 3T3-L1 preadipocytes were cultured in Dulbecco’s modified Eagle’s medium (DMEM) containing 5% calf serum at 37 oC with 5% CO2 in a humidified incubator. Differentiation was induced using DMEM with 10% fetal bovine serum supplemented with MDI two days after cell confluence (day 0). Cells were treated with 0, 10 and 100 μM melatonin on either day 0 or day 5. 72 hours after each treatment, lipid accumulation was measured by oil red O staining. Proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to membranes. As a result, lipid accumulation decreased with melatonin treatment. ERK pathway, activated when differentiation is induced, also decreased with an increase in melatonin concentration. Furthermore, the expression of key adipogenic factors, C/EBPα, C/EBPβ, and PPARγ, were reduced by melatonin treatment. These results imply that melatonin may inhibit the process of adipogenesis and may have a role as a new anti-obesity agent.
Abstract
Adipocytes are the main constituent of adipose tissue. Understanding the molecular basis of adipogenesis is pivotal to finding the therapeutic targets for treatment of obesity. Melatonin is associated with obesity and its mechanism is currently under intensive investigation. The objective of this study was to investigate the effect of melatonin on adipogenesis in differentiating preadipocytes. 3T3-L1 preadipocytes were cultured in Dulbecco’s modified Eagle’s medium (DMEM) containing 5% calf serum at 37 oC with 5% CO2 in a humidified incubator. Differentiation was induced using DMEM with 10% fetal bovine serum supplemented with MDI two days after cell confluence (day 0). Cells were treated with 0, 10 and 100 μM melatonin on either day 0 or day 5. 72 hours after each treatment, lipid accumulation was measured by oil red O staining. Proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to membranes. As a result, lipid accumulation decreased with melatonin treatment. ERK pathway, activated when differentiation is induced, also decreased with an increase in melatonin concentration. Furthermore, the expression of key adipogenic factors, C/EBPα, C/EBPβ, and PPARγ, were reduced by melatonin treatment. These results imply that melatonin may inhibit the process of adipogenesis and may have a role as a new anti-obesity agent.
참고문헌 (31)
- Formiguera X, "Obesity : epidemiology and clinical aspects", Best Pract Res Clin Gastroenterol, 18(6), pp.1125~1146 (2004)
- Kopelman PG, "Obesity as a medical problem", Nature, 404(6778), pp.635~ (2000)
- Flegal KM, "Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010", JAMA, 307(5), pp.491~497 (2012)
- Wellman NS, "Causes and consequences of adult obesity : health, social and economic impacts in the United States", Asia Pac J Clin Nutr, 11, pp.S705~S709 (2002)
- Itani O, "Short sleep duration and health outcomes : a systematic review, meta-analysis, and meta-regression", Sleep Med, 32, pp.246~256 (2017)
- Loredo JS, "Sleep Patterns and Obesity : Hispanic Community Health Study", Study of Latinos Sueño Ancillar Study, 2019, pp.156(2), 348~356
- Lefterova MI, "New developments in adipogenesis", Trends Endocrinol Metab, 20(3), pp.107~114 (2009)
- Kang MC, "Inhibition of Adipogenesis by Diphlorethohydroxycarmalol(DPHC)through AMPK Activation in Adipocytes", Mar Drugs, 17(1), pp.44~ (2019)
- Kim KS, "Anti-obesity effect of taurine through inhibition of adipogenesis in white fat tissue but not in brown fat tissue in a high-fat diet-induced obese mouse model", Amino Acids, 51(2), pp.245~254 (2019)
- Wang Y, "Conjugated linoleic acid and obesity control : efficacy and mechanisms", Int J Obesity, 28(8), pp.941~ (2004)
- Goldman S, "Autophagy and adipogenesis : implications in obesity and type II diabetes", Autophagy, 6(1), pp.179~181 (2010)
- Vermeulen K, "Apoptosis : mechanisms and relevance in cancer", Ann Hematol, 84(10), pp.627~639 (2005)
- Singletary K, "Diet, autophagy, and cancer : a review", Cancer Epidemiol Prev Biomarkers, 17(7), pp.1596~1610 (2008)
- Cipolla-Neto J, "Melatonin, energy metabolism, and obesity : a review", J Pineal Res, 56(4), pp.371~381 (2014)
- Kato H, "Melatonin promotes adipogenesis and mitochondrial biogenesis in 3T3?L1 preadipocytes", J Pineal Res, 59(2), pp.267~275 (2015)
- Zwirska-Korczala K, "Influence of melatonin on cell proliferation, antioxidative enzyme activities and lipid peroxidation in 3T3-L1 preadipocytes-an in vitro study", J Physiol Pharmacol, 56, pp.91~ (2005)
- Zhang L, "Melatonin inhibits adipogenesis and enhances osteogenesis of human mesenchymal stem cells by suppressing PPARγexpression and enhancing Runx2 expression", J Pineal Res, 49(4), pp.364~372 (2010)
- Smas CM, "Control of adipocyte differentiation", Biochem J, 309, pp.697~ (1995)
- Contreras-Alcantara S, "Removal of melatonin receptor type 1 induces insulin resistance in the mouse", Obesity, 18(9), pp.1861~1863 (2010)
- Reiter RJ, "Obesity and metabolic syndrome : association with chronodisruption, sleep deprivation, and melatonin suppression", Ann Med, 44(6), pp.564~577 (2012)
- Prusty D, "Activation of MEK", ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor γ(PPARγ)and C, J Biol Chem, pp.2002, 277(48)[DOI]
- Reiter RJ, "Melatonin as an antioxidant : biochemical mechanisms and pathophysiological implications in humans", Acta Biochim Pol, 50(4), pp.1129~1146 (2003)
- Bizzarri M, "Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer : a review", Expert Opin Ther Targets, 17(12), pp.1483~1496 (2013)
- Fernández A, "Melatonin and endoplasmic reticulum stress : relation to autophagy and apoptosis", J Pineal Res, 59(3), pp.292~307 (2015)
- Hong Y, "Melatonin treatment induces interplay of apoptosis, autophagy, and senescence in human colorectal cancer cells", J Pineal Res, 56(3), pp.264~274 (2014)
- Fu Y, "Anti-apoptotic effects of melatonin in retinal pigment epithelial cells", Front Biosci, 17(4), pp.1461~1468 (2012)
- Pazar A, "The neuroprotective and antiapoptotic effects of melatonin on hemolytic hyperbilirubinemia-induced oxidative brain damage", J Pineal Res, 60(1), pp.74~83 (2016)
- Karasek M, "Melatonin in humans", J Physiol Pharmacol, 57, pp.19~ (2006)
- Favero G, "Melatonin reduces obesity and restores adipokine patterns and metabolism in obese (ob", ob)mice, 2015, pp.35(10), 891~900
- Kayaba M, "Energy metabolism differs between sleep stages and begins to increase prior to awakening", Metabolism, 69, pp.14~23 (2017)
- Fernández Vázquez G, "Melatonin increases brown adipose tissue mass and function in Zücker diabetic fatty rats : implications for obesity control", J Pineal Res, 64(4), pp.e12472~ (2018)