Psidium guajava L. leaf extract inhibits adipocyte differentiation and improves insulin sensitivity in 3T3-L1 cells
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BACKGROUND/OBJECTIVES Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes. MATERIALS/METHODS 3T3-L1 cells were treated with 25, 50, 100 µg/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.
Abstract
BACKGROUND/OBJECTIVES Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes. MATERIALS/METHODS 3T3-L1 cells were treated with 25, 50, 100 µg/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.
참고문헌 (37)
- "IDF Diabetes Atlas" (2019)[URL]
- Chatterjee S, "Type 2 diabetes", Lancet, 389, pp.2239~2251 (2017)
- Giaccari A, "Glucose toxicity : the leading actor in the pathogenesis and clinical history of type 2 diabetes-mechanisms and potentials for treatment", Nutr Metab Cardiovasc Dis, 19, pp.365~377 (2009)
- Kalsi A, "Current treatments for type 2 diabetes, their side effects and possible complementary treatments", Int J Pharm Pharm Sci, 7, pp.13~18 (2015)
- Gutiérrez RM, "Psidium guajava : a review of its traditional uses, phytochemistry and pharmacology", J Ethnopharmacol, 117, pp.1~27 (2008)
- Khan HB, "Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats", J Diet Suppl, 10, pp.335~344 (2013)
- Ojewole JA, "Hypoglycemic and hypotensive effects of Psidium guajava Linn. (Myrtaceae) leaf aqueous extract", Methods Find Exp Clin Pharmacol, 27, pp.689~695 (2005)
- Deguchi Y, "Anti-hyperglycemic and anti-hyperlipidemic effects of guava leaf extract", Nutr Metab(Lond), 7, pp.9~ (2010)
- Wang B, "Effect of Psidium guajava leaf extract on alpha-glucosidase activity in small intestine of diabetic mouse", Sichuan Da Xue Xue Bao Yi Xue Ban, 38, pp.298~301 (2007)
- Shen SC, "Effect of guava (Psidium guajava Linn.) leaf soluble solids on glucose metabolism in type 2 diabetic rats", Phytother Res, 22, pp.1458~1464 (2008)
- Vinayagam R, "Guava leaf inhibits hepatic gluconeogenesis and increases glycogen synthesis via AMPK", ACC signaling pathways in streptozotocin-induced diabetic rats, 2018, pp.103, 1012~1017
- Beidokhti MN, "Evaluation of the antidiabetic potential of Psidium guajava L. (Myrtaceae) using assays for α-glucosidase, α-amylase, muscle glucose uptake, liver glucose production, and triglyceride accumulation in adipocytes", J Ethnopharmacol, 257, pp.112877~ (2020)
- Abel ED, "Adiposeselective targeting of the GLUT4 gene impairs insulin action in muscle and liver", Nature, 409, pp.729~733 (2001)
- Bastard JP, "Recent advances in the relationship between obesity, inflammation, and insulin resistance", Eur Cytokine Netw, 17, pp.4~12 (2006)
- McGarry JD, "Banting lecture 2001 : dysregulation of fatty acid metabolism in the etiology of type 2diabetes", Diabetes, 51, pp.7~18 (2002)
- Ali AT, "Adipocyte and adipogenesis", Eur J Cell Biol, 92, pp.229~236 (2013)
- Spiegelman BM, "Adipogenesis and obesity : rounding out the big picture", Cell, 87, pp.377~389 (1996)
- Moseti D, "Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules", Int J Mol Sci, 17, pp.124~ (2016)
- Guo X, "Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa", Izm rats by improving insulin resistance in skeletal muscle, 2013, pp.13, 52~
- Yang Q, "Guava leaf extract attenuates insulin resistance via the PI3K", Akt signaling pathway in a type 2 diabetic mouse model, 2020, pp.13, 713~718
- Sim SY, "Fucoidan from Undaria pinnatifida has anti-diabetic effects by stimulation of glucose uptake and reduction of basal lipolysis in 3T3-L1 adipocytes", Nutr Res, 65, pp.54~62 (2019)
- Kim JN, "Phytic acid and myo-inositol support adipocyte differentiation and improve insulin sensitivity in 3T3-L1 cells", Nutr Res, 34, pp.723~731 (2014)
- Tang QQ, "Mitotic clonal expansion : a synchronous process required for adipogenesis", Proc Natl Acad Sci U S A, 100, pp.44~49 (2003)
- Farmer SR, "Transcriptional control of adipocyte formation", Cell Metab, 4, pp.263~273 (2006)
- Chang E, "Natural products and obesity : a focus on the regulation of mitotic clonal expansion during adipogenesis", Molecules, 24, pp.1157~ (2019)
- Ceddia RB, "The role of AMP-activated protein kinase in regulating white adipose tissue metabolism", Mol Cell Endocrinol, 366, pp.194~203 (2013)
- Kola B, "The role of AMP-activated protein kinase in obesity", Front Horm Res, 36, pp.198~211 (2008)
- Daval M, "Functions of AMP-activated protein kinase in adipose tissue", J Physiol, 574, pp.55~62 (2006)
- Zhou Y, "Inhibitory effects of A-769662, a novel activator of AMP-activated protein kinase, on 3T3-L1 adipogenesis", Biol Pharm Bull, 32, pp.993~998 (2009)
- Habinowski SA, "The effects of AICAR on adipocyte differentiation of 3T3-L1 cells", Biochem Biophys Res Commun, 286, pp.852~856 (2001)
- Langin D, "Adipocyte lipases and defect of lipolysis in human obesity", Diabetes, 54, pp.3190~3197 (2005)
- Lafontan M, "Lipolysis and lipid mobilization in human adipose tissue", Prog Lipid Res, 48, pp.275~297 (2009)
- Morigny P, "Adipocyte lipolysis and insulin resistance", Biochimie, 125, pp.259~266 (2016)
- Boden G, "Mechanisms of fatty acid-induced inhibition of glucose uptake", J Clin Invest, 93, pp.2438~2446 (1994)
- Lam TK, "Mechanisms of the free fatty acidinduced increase in hepatic glucose production", Am J Physiol Endocrinol Metab, 284, pp.E863~E873 (2003)
- 전상민, "Regulation and function of AMPK in physiology and diseases", Experimental and Molecular Medicine, 48, pp.1~13 (2016), 생화학분자생물학회
- Bijland S, "Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation", Clin Sci(Lond), 124, pp.491~507 (2013)