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      Restoration of the adipogenic gene expression by naringenin and naringin in 3T3-L1 adipocytes

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      https://www.riss.kr/link?id=A107793223

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      다국어 초록 (Multilingual Abstract)

      Background: Naringenin and its glycoside naringin are well known citrus flavonoids with several therapeutic benefits. Although the anti-adipogenic effects of naringenin and naringin have been reported previously, the detailed mechanism underlying thei...

      Background: Naringenin and its glycoside naringin are well known citrus flavonoids with several therapeutic benefits. Although the anti-adipogenic effects of naringenin and naringin have been reported previously, the detailed mechanism underlying their anti-adipogenesis effects is poorly understood.
      Objectives: This study examined the anti-adipogenic effects of naringenin and naringin by determining differential gene expression patterns in these flavonoids-treated 3T3-L1 adipocytes.
      Methods: Lipid accumulation and triglyceride (TG) content were determined by Oil red O staining and TG assay. Glucose uptake was measured using a 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose fluorescent d-glucose analog. The phosphorylation levels of AMP-activated protein kinase (AMPK) and acetyl Co-A carboxylase (ACC) were observed via Western blot analysis. Differential gene expressions in 3T3-L1 adipocytes were evaluated via RNA sequencing analysis.
      Results: Naringenin and naringin inhibited both lipid accumulation and TG content, increased phosphorylation levels of both AMPK and ACC and decreased the expression level of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) in 3T3-L1 adipocytes. RNA sequencing analysis revealed that 32 up-regulated (> 2-fold) and 17 down-regulated (< 0.6-fold) genes related to lipid metabolism, including Acaca, Fasn, Scd1, Mogat1, Dgat, Lipin1, Cpt1a, and Lepr, were normalized to the control level in naringenin-treated adipocytes. In addition, 25 up-regulated (> 2-fold) and 25 down-regulated (< 0.6-fold) genes related to lipid metabolism, including Acaca, Fasn, Fabp5, Scd1, Srebf1, Hmgcs1, Cpt1c, Lepr, and Lrp1, were normalized to the control level by naringin.
      Conclusions: The results indicate that naringenin and naringin have anti-adipogenic potentials that are achieved by normalizing the expression levels of lipid metabolism-related genes that were perturbed in differentiated 3T3-L1 cells.

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      참고문헌 (Reference)

      1 Rajappa R, "Treatment with naringenin elevates the activity of transcription factor Nrf2 to protect pancreatic β-cells from streptozotocin-induced diabetes in vitro and in vivo" 9 : 1562-, 2019

      2 Goldwasser J, "Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: role of PPARalpha, PPARgamma and LXRalpha" 5 (5): e12399-, 2010

      3 Ha T, "The selected flavonol glycoside derived from Sophorae Flos improves glucose uptake and inhibits adipocyte differentiation via activation AMPK in 3T3-L1 cells" 20 (20): 6076-6081, 2010

      4 Actis Dato V, "The role of low-density lipoprotein receptor-related protein 1 in lipid metabolism, glucose homeostasis and inflammation" 19 (19): 1780-, 2018

      5 Ceddia RB, "The role of AMP-activated protein kinase in regulating white adipose tissue metabolism" 366 (366): 194-203, 2013

      6 Guaita-Esteruelas S, "The peritumoural adipose tissue microenvironment and cancer. The roles of fatty acid binding protein 4 and fatty acid binding protein 5" 462 (462): 107-118, 2018

      7 Havsteen BH, "The biochemistry and medical significance of the flavonoids" 96 (96): 67-202, 2002

      8 Matsumoto H, "The SNPs in the ACACA gene are effective on fatty acid composition in Holstein milk" 39 (39): 8637-8644, 2012

      9 Guo X, "Synergistic interactions of apigenin, naringin, quercetin and emodin on inhibition of 3T3-L1 preadipocyte differentiation and pancreas lipase activity" 10 (10): 327-339, 2016

      10 Jiang Z, "Significant associations of stearoylCoA desaturase(SCD1)gene with fat deposition and composition in skeletal muscle" 4 (4): 345-351, 2008

      1 Rajappa R, "Treatment with naringenin elevates the activity of transcription factor Nrf2 to protect pancreatic β-cells from streptozotocin-induced diabetes in vitro and in vivo" 9 : 1562-, 2019

      2 Goldwasser J, "Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: role of PPARalpha, PPARgamma and LXRalpha" 5 (5): e12399-, 2010

      3 Ha T, "The selected flavonol glycoside derived from Sophorae Flos improves glucose uptake and inhibits adipocyte differentiation via activation AMPK in 3T3-L1 cells" 20 (20): 6076-6081, 2010

      4 Actis Dato V, "The role of low-density lipoprotein receptor-related protein 1 in lipid metabolism, glucose homeostasis and inflammation" 19 (19): 1780-, 2018

      5 Ceddia RB, "The role of AMP-activated protein kinase in regulating white adipose tissue metabolism" 366 (366): 194-203, 2013

      6 Guaita-Esteruelas S, "The peritumoural adipose tissue microenvironment and cancer. The roles of fatty acid binding protein 4 and fatty acid binding protein 5" 462 (462): 107-118, 2018

      7 Havsteen BH, "The biochemistry and medical significance of the flavonoids" 96 (96): 67-202, 2002

      8 Matsumoto H, "The SNPs in the ACACA gene are effective on fatty acid composition in Holstein milk" 39 (39): 8637-8644, 2012

      9 Guo X, "Synergistic interactions of apigenin, naringin, quercetin and emodin on inhibition of 3T3-L1 preadipocyte differentiation and pancreas lipase activity" 10 (10): 327-339, 2016

      10 Jiang Z, "Significant associations of stearoylCoA desaturase(SCD1)gene with fat deposition and composition in skeletal muscle" 4 (4): 345-351, 2008

      11 Kang SW, "Sasa quelpaertensis Nakai extract and its constituent p-coumaric acid inhibit adipogenesis in 3T3-L1 cells through activation of the AMPK pathway" 59 : 380-385, 2013

      12 Eberlé D, "SREBF-1 gene polymorphisms are associated with obesity and type 2 diabetes in French obese and diabetic cohorts" 53 (53): 2153-2157, 2004

      13 Morand C, "Respective bioavailability of quercetin aglycone and its glycosides in a rat model" 12 (12): 169-174, 2000

      14 Hardie DG, "Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase" 30 (30): 1064-1070, 2002

      15 Hillgartner FB, "Physiological and molecular mechanisms involved in nutritional regulation of fatty acid synthesis" 75 (75): 47-76, 1995

      16 Smith SJ, "Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat" 25 (25): 87-90, 2000

      17 Xu L, "Natural products for the treatment of type 2 diabetes mellitus : Pharmacology and mechanisms" 130 : 451-465, 2018

      18 Sun NN, "Natural dietary and herbal products in anti-obesity treatment" 21 (21): 1351-, 2016

      19 Ribeiro IA, "Naringin and naringenin determination and control in grapefruit juice by a validated HPLC method" 19 (19): 432-438, 2008

      20 Pu P, "Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet" 518 (518): 61-70, 2012

      21 Rebello CJ, "Naringenin promotes thermogenic gene expression in human white adipose tissue" 27 (27): 103-111, 2019

      22 Richard AJ, "Naringenin inhibits adipogenesis and reduces insulin sensitivity and adiponectin expression in adipocytes" 2013 : 549750-, 2013

      23 Constantin RP, "Molecular mechanisms of citrus flavanones on hepatic gluconeogenesis" 92 : 148-162, 2014

      24 Péterfy M, "Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin" 27 (27): 121-124, 2001

      25 Rizzatti V, "Lipid droplets characterization in adipocyte differentiated 3T3-L1 cells: size and optical density distribution" 57 (57): e24-, 2013

      26 Fang XK, "Kaempferol and quercetin isolated from Euonymus alatus improve glucose uptake of 3T3-L1 cells without adipogenesis activity" 82 (82): 615-622, 2008

      27 Mauvoisin D, "Hormonal and nutritional regulation of SCD1 gene expression" 93 (93): 78-86, 2011

      28 Křen V, "Glycoscience" Springer 2589-2644, 2008

      29 Quintana AM, "Functional analysis of the zebrafish ortholog of HMGCS1reveals independent functions for cholesterol and isoprenoids in craniofacial development" 12 (12): e0180856-, 2017

      30 Veitch NC, "Flavonoids and their glycosides, including anthocyanins" 28 (28): 1626-1695, 2011

      31 Ameer B, "Flavanone absorption after naringin, hesperidin, and citrus administration" 60 (60): 34-40, 1996

      32 Langmead B, "Fast gapped-read alignment with Bowtie 2" 9 (9): 357-359, 2012

      33 Hall AM, "Evidence for regulated monoacylglycerol acyltransferase expression and activity in human liver" 53 (53): 990-999, 2012

      34 Gao XF, "Enhanced susceptibility of Cpt1c knockout mice to glucose intolerance induced by a high-fat diet involves elevated hepatic gluconeogenesis and decreased skeletal muscle glucose uptake" 52 (52): 912-920, 2009

      35 Lien DN, "Effect of pomelo (citrus grandis (l). osbeck) peel extract on lipid-carbohydrate metabolic enzymes and blood lipid, glucose parameters in experimental obese and diabetic mice" 26 (26): 224-232, 2010

      36 Claussnitzer M, "Effect of flavonoids on basal and insulinstimulated 2-deoxyglucose uptake in adipocytes" 55 (55): S26-S34, 2011

      37 Alam MA, "Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action" 5 (5): 404-417, 2014

      38 Jung UJ, "Effect of citrus flavonoids on lipid metabolism and glucoseregulating enzyme mRNA levels in type-2 diabetic mice" 38 (38): 1134-1145, 2006

      39 Xiao J, "Dietary flavonoid aglycones and their glycosides: Which show better biological significance?" 57 (57): 1874-1905, 2017

      40 Harris CA, "DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes" 52 (52): 657-667, 2011

      41 Hsiu SL, "Comparison of metabolic pharmacokinetics of naringin and naringenin in rabbits" 70 (70): 1481-1489, 2002

      42 Lee SH, "Cholesterol-lowering activity of naringenin via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A : cholesterol acyltransferase in rats" 43 (43): 173-180, 1999

      43 Kumar S, "Chemistry and biological activities of flavonoids : an overview" 2013 : 162750-, 2013

      44 Bjørbaek C, "Central leptin receptor action and resistance in obesity" 57 (57): 789-794, 2009

      45 Bonnefont JP, "Carnitine palmitoyltransferases 1and 2: biochemical, molecular and medical aspects" 25 (25): 495-520, 2004

      46 Park J, "Bitter orange(Citrus aurantium Linné)improves obesity by regulating adipogenesis and thermogenesis through AMPK activation" 11 (11): 1988-, 2019

      47 Gentleman RC, "Bioconductor: open software development for computational biology and bioinformatics" 5 (5): R80-, 2004

      48 Mahmoud AM, "Beneficial effects of citrus flavonoids on cardiovascular and metabolic health" 2019 : 5484138-, 2019

      49 Morton GJ, "Arcuate nucleusspecific leptin receptor gene therapy attenuates the obesity phenotype of Koletsky(fa(k)/fa(k))rats" 144 (144): 2016-2024, 2003

      50 Sachithra S. Ranaweera, "Anti-inflammatory effect of sulforaphane on LPS-stimulated RAW 264.7 cells and ob/ob mice" 대한수의학회 21 (21): 0-0, 2020

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      학술지 이력

      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
      2020-01-01 평가 등재학술지 유지 (해외등재 학술지 평가) KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2006-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2005-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2003-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      학술지 인용정보
      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 1.08 0.11 0.76
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.61 0.51 0.245 0.05
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