Metformin inhibits macrophage cholesterol biosynthesis rate: Possible role for metformin-induced oxidative stress

Biochemical and Biophysical Research Communications

Volumn 439, Issue 3, 2013, Pages 396-400

  Koren Gluzer, Marie ^a   Aviram, Michael ^a   Hayek, Tony ^a  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

Author keywords

Cholesterol biosynthesis; Diabetes; Macrophages; Metformin; Oxidative stress

Indexed keywords

ACETIC ACID; ALPHA TOCOPHEROL; ARYLDIALKYLPHOSPHATASE 2; CHOLESTEROL; GLUTATHIONE; METFORMIN; MEVALONIC ACID; REACTIVE OXYGEN METABOLITE; SIMVASTATIN;

ANIMAL CELL; ARTICLE; ATHEROGENESIS; CHOLESTEROL SYNTHESIS; CONTROLLED STUDY; LIPID STORAGE; MACROPHAGE; MOUSE; NONHUMAN; OXIDATION; OXIDATIVE STRESS; POMEGRANATE JUICE; PRIORITY JOURNAL; PROTEIN EXPRESSION; STIMULATION;

3-HYDROXY-3-METHYL-GLUTARYL-COA; AMP-ACTIVATED PROTEIN KINASE; AMPK; CHOLESTEROL BIOSYNTHESIS; DIABETES; GLUTATHIONE; GSH; HMG-COA; MACROPHAGES; METFORMIN; MF; OS; OXIDATIVE STRESS; PARAOXONASE2; PJ; POMEGRANATE JUICE; PON2; REACTIVE OXYGEN SPECIES; ROS; T2DM; TYPE 2 DIABETES MELLITUS; VE; VITAMIN E;

ANIMALS; ANTIOXIDANTS; CELL LINE; CHOLESTEROL; HYPOGLYCEMIC AGENTS; MACROPHAGES; METFORMIN; MICE; OXIDATIVE STRESS; VITAMIN E;

LYTHRACEAE;

EID: 84884596941     PISSN: 0006291X     EISSN: 10902104     Source Type: Journal    
DOI: 10.1016/j.bbrc.2013.08.062     Document Type: Article

References (27)

1. Tiwari R.L., Singh V., Barthwal M.K. Macrophages: an elusive yet emerging therapeutic target of atherosclerosis. Med. Res. Rev. 2008, 28(4):483-544.
2. Lusis A.J. Atherosclerosis. Nature 2000, 407(6801):233-241.
3. Aviram M. Modified forms of low density lipoprotein and atherosclerosis. Atherosclerosis 1993, 98(1):1-9.
4. Witztum J.L., Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J. Clin. Invest. 1991, 88(6):1785-1792.
5. Kaplan M., Aviram M., Hayek T. Oxidative stress and macrophage foam cell formation during diabetes mellitus-induced atherogenesis: role of insulin therapy. Pharmacol. Ther. 2012, 136(2):175-185.
6. Bowden D.W., Cox A.J., Freedman B.I., Hugenschimdt C.E., Wagenknecht L.E., Herrington D., Agarwal S., Register T.C., Maldjian J.A., Ng M.C., et al. Review of the Diabetes Heart Study (DHS) family of studies: a comprehensively examined sample for genetic and epidemiological studies of type 2 diabetes and its complications. Rev. Diabet. Stud. 2010, 7(3):188-201.
7. Hong J., Zhang Y., Lai S., Lv A., Su Q., Dong Y., Zhou Z., Tang W., Zhao J., Cui L., et al. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care 2013, 36(5):1304-1311.
8. Alexandre K.B., Smit A.M., Gray I.P., Crowther N.J. Metformin inhibits intracellular lipid accumulation in the murine pre-adipocyte cell line, 3T3-L1. Diabetes Obes. Metab. 2008, 10(8):688-690.
9. Collier C.A., Bruce C.R., Smith A.C., Lopaschuk G., Dyck D.J. Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 2006, 291(1):E182-E189.
10. Zang M., Zuccollo A., Hou X., Nagata D., Walsh K., Herscovitz H., Brecher P., Ruderman N.B., Cohen R.A. AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin-resistant human HepG2 cells. J. Biol. Chem. 2004, 279(46):47898-47905.
11. Kawaguchi T., Osatomi K., Yamashita H., Kabashima T., Uyeda K. Mechanism for fatty acid "sparing" effect on glucose-induced transcription: regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase. J. Biol. Chem. 2002, 277(6):3829-3835.
12. Foretz M., Viollet B. Regulation of hepatic metabolism by AMPK. J. Hepatol. 2011, 54(4):827-829.
13. Schneider J., Erren T., Zofel P., Kaffarnik H. Metformin-induced changes in serum lipids, lipoproteins, and apoproteins in non-insulin-dependent diabetes mellitus. Atherosclerosis 1990, 82(1-2):97-103.
14. Schneider J. Effects of metformin on dyslipoproteinemia in non-insulin-dependent diabetes mellitus. Diab. Metab. 1991, 17(1 Pt. 2):185-190.
15. Abbasi F., Chu J.W., McLaughlin T., Lamendola C., Leary E.T., Reaven G.M. Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus. Metabolism 2004, 53(2):159-164.
16. Rosen P., Wiernsperger N.F. Metformin delays the manifestation of diabetes and vascular dysfunction in Goto-Kakizaki rats by reduction of mitochondrial oxidative stress. Diab. Metab. Res. Rev. 2006, 22(4):323-330.
17. Bonnefont-Rousselot D., Raji B., Walrand S., Gardes-Albert M., Jore D., Legrand A., Peynet J., Vasson M.P. An intracellular modulation of free radical production could contribute to the beneficial effects of metformin towards oxidative stress. Metabolism 2003, 52(5):586-589.
18. Shackelford D.B., Shaw R.J. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer 2009, 9(8):563-575.
19. Anedda A., Rial E., Gonzalez-Barroso M.M. Metformin induces oxidative stress in white adipocytes and raises uncoupling protein 2 levels. J. Endocrinol. 2008, 199(1):33-40.
20. Seeram N.P., Aviram M., Zhang Y., Henning S.M., Feng L., Dreher M., Heber D. Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States. J. Agric. Food Chem. 2008, 56(4):1415-1422.
21. Rosenblat M., Coleman R., Aviram M. Increased macrophage glutathione content reduces cell-mediated oxidation of LDL and atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 2002, 163(1):17-28.
22. Shiner M., Fuhrman B., Aviram M. Macrophage paraoxonase 2 (PON2) expression is up-regulated by pomegranate juice phenolic anti-oxidants via PPAR gamma and AP-1 pathway activation. Atherosclerosis 2007, 195(2):313-321.
23. Hardie D.G. Neither LKB1 nor AMPK are the direct targets of metformin. Gastroenterology 2006, 131(3):973. author reply 974-975.
24. Owen M.R., Doran E., Halestrap A.P. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J. 2000, 348(Pt 3):607-614.
25. Fuhrman B., Oiknine J., Aviram M. Iron induces lipid peroxidation in cultured macrophages, increases their ability to oxidatively modify LDL, and affects their secretory properties. Atherosclerosis 1994, 111(1):65-78.
26. Fuhrman B., Judith O., Keidar S., Ben-Yaish L., Kaplan M., Aviram M. Increased uptake of LDL by oxidized macrophages is the result of an initial enhanced LDL receptor activity and of a further progressive oxidation of LDL. Free Radic. Biol. Med. 1997, 23(1):34-46.
27. Bjorkhem I. Do oxysterols control cholesterol homeostasis?. J. Clin. Invest. 2002, 110(6):725-730.