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http://dx.doi.org/10.5483/BMBRep.2013.46.4.153

Caffeine attenuates lipid accumulation via activation of AMP-activated protein kinase signaling pathway in HepG2 cells  

Quan, Hai Yan (Department of Pharmacology and Clinical Pharmacy, College of Pharmacy, Kyung Hee University)
Kim, Do Yeon (Department of Pharmacology and Clinical Pharmacy, College of Pharmacy, Kyung Hee University)
Chung, Sung Hyun (Department of Pharmacology and Clinical Pharmacy, College of Pharmacy, Kyung Hee University)
Publication Information
BMB Reports / v.46, no.4, 2013 , pp. 207-212 More about this Journal
Abstract
The main purpose of this study is to examine the effect of caffeine on lipid accumulation in human hepatoma HepG2 cells. Significant decreases in the accumulation of hepatic lipids, such as triglyceride (TG), and cholesterol were observed when HepG2 cells were treated with caffeine as indicated. Caffeine decreased the mRNA level of lipogenesis-associated genes (SREBP1c, SREBP2, FAS, SCD1, HMGR and LDLR). In contrast, mRNA level of CD36, which is responsible for lipid uptake and catabolism, was increased. Next, the effect of caffeine on AMP-activated protein kinase (AMPK) signaling pathway was examined. Phosphorylation of AMPK and acetyl-CoA carboxylase were evidently increased when the cells were treated with caffeine as indicated for 24 h. These effects were all reversed in the presence of compound C, an AMPK inhibitor. In summary, these data indicate that caffeine effectively depleted TG and cholesterol levels by inhibition of lipogenesis and stimulation of lipolysis through modulating AMPK-SREBP signaling pathways.
Keywords
AMP-activated protein kinase; Caffeine; HepG2 cells; Lipid accumulation; Sterol regulatory element-binding protein;
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1 Hardie, D. G. and Pan, D. A. (2002) Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase. Biochem. Soc. Trans. 30, 1064-1070.   DOI
2 Paynter, N. P., Yeh, H. C., Voutilainen, S., Schmidt, M. I., Heiss, G., Folsom, A. R., Brancati, F. L. and Kao, W. H. (2006) Coffee and sweetened beverage consumption and the risk of type 2 diabetes mellitus: the atherosclerosis risk in communities study. Am. J. Epidemiol. 164, 1075-1084.   DOI   ScienceOn
3 Tuomilehto, J., Hu, G., Bidel, S., Lindstrom, J. and Jousilahti, P. (2004) Coffee consumption and risk of type 2 diabetes mellitus among middle-aged Finnish men and women. JAMA 291, 1213-1219.   DOI   ScienceOn
4 McCarty, M. F. (2005) A chlorogenic acid-induced increase in GLP-1 production may mediate the impact of heavy coffee consumption on diabetes risk. Med. Hypotheses 64, 848-853.   DOI   ScienceOn
5 Nakabayashi, H., Hashimoto, T., Ashida, H., Nishiumi, S. and Kanazawa, K. (2008) Inhibitory effects of caffeine and its metabolites on intracellular lipid accumulation in murine 3T3-L1 adipocytes. Biofactors 34, 293-302.   DOI
6 Murosaki, S., Lee, T. R., Muroyama, K., Shin, E. S., Cho, S. Y., Yamamoto, Y. and Lee, S. J. (2007) A combination of caffeine, arginine, soy isoflavones, and L-carnitine enhances both lipolysis and fatty acid oxidation in 3T3-L1 and HepG2 cells in vitro and in KK mice in vivo. J. Nutr. 137, 2252-2257.   DOI
7 Eberle, D., Hegarty, B., Bossard, P., Ferré, P. and Foufelle, F. (2004) SREBP transcription factors: master regulators of lipid homeostasis. Biochimi. 86, 839-848.   DOI   ScienceOn
8 Kim, S. J., Jung, J. Y., Kim, H. W. and Park, T. (2008) Anti-obesity effects of Juniperus chinensis extract are associated with increased AMP-activated protein kinase expression and phosphorylation in the visceral adipose tissue of rats. Biol. Pharm. Bull. 31, 415-421.
9 Ching, Y. P., Davies, S. P. and Hardie, D. G. (1996) Analysis of the specificity of the AMP-activated protein kinase by site-directed mutagenesis of bacterially expressed 3-hydroxy 3-methylglutaryl-CoA reductase, using a single primer variant of the unique-site-elimination method. Eur. J. Biochem. 237, 800-808.   DOI   ScienceOn
10 Pallottini, V., Montanari, L., Cavallini, G., Bergamini, E., Gori, Z. and Trentalance, A. (2004) Mechanisms underlying the impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in aged rat liver. Mech. Ageing Dev. 125, 633-639.   DOI   ScienceOn
11 Department of Agriculture Agricultural Research Service: USDA. National Nutrient Database for Standard Reference (2007).
12 Nagle, C. A., Klett, E. L. and Coleman, R. A. (2009) Hepatic triacylglycerol accumulation and insulin resistance. J. Lipid Res. 50, S74-79.   DOI
13 Summers, S. A. (2006) Ceramide in insulin resistance and lipotoxicity. Prog. Lipid Res. 45, 42-72.   DOI   ScienceOn
14 Horton, J. D., Goldstein, J. L. and Brown, M. S. (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 109, 1125-1131.   DOI
15 Saha, A. K. and Ruderman, N. B. (2003) Malonyl-CoA and AMP-activated protein kinase: an expanding partnership. Mol. Cell Biochem. 253, 65-70.   DOI   ScienceOn
16 Hardie, D. G. (2008) AMPK: a key regulator of energy balance in the single cell and the whole organism. Int. J. Obes. 32, S7-S12.   DOI
17 Hardie, D. G., Corton, J., Ching, Y. P., Davies, S. P. and Hawley, S. (1997) Regulation of lipid metabolism by the AMP-activated protein kinase. Biochem. Soc. Trans. 25, 1229-1231.   DOI
18 Porstmann, T., Santos, C. R., Griffiths, B., Cully, M., Wu, M., Leevers, S., Griffiths, J. R., Chung, Y. L. and Schulze, A. (2008) SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab. 8, 224-236.   DOI   ScienceOn
19 You, M., Matsumoto, M., Pacold, C. M., Cho, W. K. and Crabb, D. W. (2004) The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology 127, 1798-1808.   DOI   ScienceOn
20 Lee, W. J. (2006) AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARa and PGC-1. Biochem. Biophys. Res. Commun. 340, 281-295.
21 Keijzers, G. B., De Galan, B. E., Tack, C. J. and Smits P. (2002) Caffeine can decrease insulin sensitivity in humans. Diabetes Care 25, 364-369.   DOI   ScienceOn
22 Duffey, K. J. and Popkin, B. M. (2007) Shifts in patterns and consumption of beverages between 1965 and 2002. Obesity 15, 2739-2747.   DOI   ScienceOn
23 Marchesini, G., Brizi, M., Bianchi, G., Tomassetti, S., Buqianesi, E., Lenzi, M., McCullough, A., Natale, S., Forlani, G. and Melchionda, N. (2001) Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 50, 1884-1850.