256
Views
31
CrossRef citations to date
0
Altmetric
Review

α-Lipoic acid: physiologic mechanisms and indications for the treatment of metabolic syndrome

Pages 291-302 | Published online: 16 Feb 2007

Bibliography

  • HALLIWELL B: Antioxidants in human health and disease. Ann. Rev. Nutr. (1996) 16:33-50.
  • GUTTERIDGE JM, HALLIWELL B: Free radicals and antioxidants in the year 2000. A historical look to the future. Ann. NY Acad. Sci. (2000) 899:136-147.
  • WINROW VR, WINYARD PG, MORRIS DJ, BLAKE DR: Free radicals in inflammation: second messengers and mediators of tissue destruction. Br. Med. Bull. (1993) 49:506-522.
  • SEN CK, PACKER L: Antioxidant and redox regulation of gene transcription. FASEB J. (1996) 10:709-720.
  • LIU J, ATAMNA H, KURATSUNE H, AMES BN: Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann. NY Acad. Sci. (2002) 959:133-166.
  • PACKER L, TRITSCHLER HJ, WESSEL K: Neuroprotection by the metabolic antioxidant α-lipoic acid. Free Radic. Biol. Med. (1997) 22:359-378.
  • PODDA M, GRUNDMANN-KOLLMANN M: Low molecular weight antioxidants and their role in skin ageing. Clin. Exp. Dermatol. (2001) 26:578-582.
  • BAYNES JW: Role of oxidative stress in development of complications in diabetes. Diabetes (1991) 40:405-412.
  • BLOCH-DAMTI A, BASHAN N: Proposed mechanisms for the induction of insulin resistance by oxidative stress. Antioxid. Redox Signal. (2005) 7:1553-1567.
  • FRISARD M, RAVUSSIN E: Energy metabolism and oxidative stress: impact on the metabolic syndrome and the aging process. Endocrine (2006) 29:27-32.
  • BIEWENGA GP, HAENEN GR, BAST A: The pharmacology of the antioxidant lipoic acid. Gen. Pharmacol. (1997) 29:315-331.
  • FUCHS J, PACKER L, ZIMMER G: Lipoic Acid in Health and Disease. 1st Edition, Marcel Dekker, Inc., London, UK (1997).
  • EVANS JL, MADDUX BA, GOLDFINE ID: The molecular basis for oxidative stress-induced insulin resistance. Antioxid. Redox Signal. (2005) 7:1040-1052.
  • EVANS JL, YOUNGREN JF, GOLDFINE ID: Effective treatments for insulin resistance: trim the fat and douse the fire. Trends Endocrinol. Metab. (2004) 15:425-431.
  • BAST A, HAENEN GR: Interplay between lipoic acid and glutathione in the protection against microsomal lipid peroxidation. Biochim. Biophys. Acta (1988) 963:558-561.
  • LINNANE AW, EASTWOOD H: Cellular redox regulation and prooxidant signaling systems: a new perspective on the free radical theory of aging. Ann. NY Acad. Sci. (2006) 1067:47-55.
  • CAKATAY U: Pro-oxidant actions of α-lipoic acid and dihydrolipoic acid. Med. Hypotheses (2006) 66:110-117.
  • MOINI H, PACKER L, SARIS NE: Antioxidant and prooxidant activities of α-lipoic acid and dihydrolipoic acid. Toxicol. Appl. Pharmacol. (2002) 182:84-90.
  • KONRAD D: Utilization of the insulin-signaling network in the metabolic actions of α-lipoic acid-reduction or oxidation? Antioxid. Redox Signal. (2005) 7:1032-1039.
  • BHATTI F, MANKHEY RW, ASICO L, QUINN MT, WELCH WJ, MARIC C: Mechanisms of antioxidant and prooxidant effects of α-lipoic acid in the diabetic and nondiabetic kidney. Kidney Int. (2005) 67:1371-1380.
  • PERSHADSINGH HA, HO CI, RAJAMANI J et al.: α-Lipoic acid is a weak dual PPARα/γ agonist: an ester derivative with increased PPARα/γ activity. J. Applied Res. (2005) 5:510-523.
  • TSIEN RY: Intracellular measurements of ion activities. Ann. Rev. Biophys. Bioeng. (1983) 12:91-116.
  • LEUNG M, KWONG S, HOU S et al.: Deficiency of the Nrf1 and Nrf2 transcription factors results in early embryonic lethality and severe oxidative stress. J. Biol. Chem. (2003) 278:48021-48029.
  • KAHN BB, ALQUIER T, CARLING D, HARDIE DG: AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. (2005) 1:15-25.
  • LONG YC, ZIERATH JR: AMP-activated protein kinase signaling in metabolic regulation. J. Clin. Invest. (2006) 116:1776-1783.
  • WINDER WW, HARDIE DG: Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am. J. Physiol. (1996) 270:E299-E304.
  • ZHOU G, MYERS R, LI Y et al.: Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. (2001) 108:1167-1174.
  • MUSI N, HIRSHMAN MF, NYGREN J et al.: Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with Type 2 diabetes. Diabetes (2002) 51:2074-2081.
  • FRYER LG, PARBU-PATEL A, CARLING D: The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J. Biol. Chem. (2002) 12(277):25226-25232.
  • SAHA AK, AVILUCEA PR, YE JM, ASSIFI MM, KRAEGEN EW, RUDERMAN NB: Pioglitazone treatment activates AMP-activated protein kinase in rat liver and adipose tissue in vivo. Biochem. Biophys. Res. Commun. (2004) 314:580-585.
  • MUSI N, FUJII N, HIRSHMAN MF et al.: AMP-activated protein kinase (AMPK) is activated in muscle of subjects with Type 2 diabetes during exercise. Diabetes (2001) 50:921-927.
  • LEHMANN JM, MOORE LB, SMITH-OLIVER TA, WILKISON WO, WILLSON TM, KLIEWER SA: An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPAR γ). J. Biol. Chem. (1995) 270:12953-12956.
  • RUDERMAN N, FLIER JS: Chewing the fat-ACC and energy balance. Science (2001) 291:2558-2559.
  • JACOB S, STREEPER RS, FOGT DL et al.: The antioxidant α-lipoic acid enhances insulin-stimulated glucose metabolism in insulin-resistant rat skeletal muscle. Diabetes (1996) 45:1024-1029.
  • KHAMAISI M, POTASHNIK R, TIROSH A et al.: Lipoic acid reduces glycemia and increases muscle GLUT4 content in streptozotocin-diabetic rats. Metabolism (1997) 46:763-768.
  • KHAMAISI M, RUDICH A, POTASHNIK R, TRITSCHLER HJ, GUTMAN A, BASHAN N: Lipoic acid acutely induces hypoglycemia in fasting non-diabetic and diabetic rats. Metabolism (1999) 48:504-510.
  • EASON RC, ARCHER HE, AKHTAR S, BAILEY CJ: Lipoic acid increases glucose uptake by skeletal muscles of obese-diabetic ob/ob mice. Diabetes Obes. Metab. (2002) 4:29-35.
  • MIDAOUI AE, DE CHAMPLAIN J: Prevention of hypertension, insulin resistance, and oxidative stress by α-lipoic acid. Hypertension (2002) 39:303-307.
  • MIDAOUI AE, ELIMADI A, WU L, HADDAD PS, DE CHAMPLAIN J: Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production. Am. J. Hypertens. (2003) 16:173-179.
  • SONG KH, LEE WJ, KOH JM et al.: α-Lipoic acid prevents diabetes mellitus in diabetes-prone obese rats. Biochem. Biophys. Res. Commun. (2005) 326:197-202.
  • JACOB S, HENRIKSEN EJ, TRITSCHLER HJ, AUGUSTIN HJ, DIETZE GJ: Improvement of insulin-stimulated glucose-disposal in Type 2 diabetes after repeated parenteral administration of thioctic acid. Exp. Clin. Endocrinol. Diabetes (1996) 104:284-288.
  • JACOB S, RUUS P, HERMANN R et al.: Oral administration of RAC-α-lipoic acid modulates insulin sensitivity in patients with Type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radic. Biol. Med. (1999) 27:309-314.
  • KONRAD T, VICINI P, KUSTERER K et al.: α-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with Type 2 diabetes. Diabetes Care (1999) 22:280-287.
  • BORCEA V, NOUROOZ-ZADEH J, WOLFF SP et al.: α-Lipoic acid decreases oxidative stress even in diabetic patients with poor glycemic control and albuminuria. Free Radic. Biol. Med. (1999) 26:1495-1500.
  • ROSEN P, NAWROTH PP, KING G, MOLLER W, TRITSCHLER HJ, PACKER L: The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab. Res. Rev. (2001) 17:189-212.
  • EVANS JL, HEYMANN CJ, GOLDFINE ID, GAVIN LA: Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of α-lipoic acid. Endocr. Pract. (2002) 8:29-35.
  • PAN DA, LILLIOJA S, MILNER MR et al.: Skeletal muscle membrane lipid composition is related to adiposity and insulin action. J. Clin. Invest. (1995) 96:2802-2808.
  • KELLEY DE, SLASKY S, JANOSKY J: Skeletal muscle density: effects of obesity and non-insulin-dependent diabetes mellitus. Am. J. Clin. Nutr. (1991) 54:509-515.
  • KELLEY DE, GOODPASTER BH: Skeletal muscle triglyceride. An aspect of regional adiposity and insulin resistance. Diabetes Care (2001) 24:933-941.
  • LEE WJ, SONG KH, KOH EH et al.: α-Lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem. Biophys. Res. Commun. (2005) 332:885-891.
  • MINOKOSHI Y, ALQUIER T, FURUKAWA N et al.: AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature (2004) 428:569-574.
  • ANDERSSON U, FILIPSSON K, ABBOTT CR et al.: AMP-activated protein kinase plays a role in the control of food intake. J. Biol. Chem. (2004) 279(13):12005-12008.
  • KIM MS, PARK JY, NAMKOONG C et al.: Anti-obesity effects of α-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nat. Med. (2004) 10:727-733.
  • LEE WJ, KOH EH, WON JC, KIM MS, PARK JY, LEE KU: Obesity: the role of hypothalamic AMP-activated protein kinase in body weight regulation. Int. J. Biochem. Cell Biol. (2005) 37:2254-2259.
  • SPIEGELMAN BM: Peroxisome proliferator-activated receptor γ: a key regulator of adipogenesis and systemic insulin sensitivity. Eur. J. Med. Res. (1997) 2:457-464.
  • WILLSON TM, BROWN PJ, STERNBACH DD, HENKE BR: The PPARs: from orphan receptors to drug discovery. J. Med. Chem. (2000) 43:527-550.
  • MOLLER DE: New drug targets for Type 2 diabetes and the metabolic syndrome. Nature (2001) 414:821-827.
  • MOLLER DE, KAUFMAN KD: Metabolic syndrome: a clinical and molecular perspective. Ann. Rev. Med. (2005) 56:45-62.
  • KLIEWER SA, UMESONO K, NOONAN DJ, HEYMAN RA, EVANS RM: Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature (1992) 358:771-774.
  • BENSON SC, PERSHADSINGH HA, HO CI et al.: Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARγ-modulating activity. Hypertension (2004) 43:993-1002.
  • EL MIDAOUI A, WU L, WANG R, DE CHAMPLAIN J: Modulation of cardiac and aortic peroxisome proliferator-activated receptor-γ expression by oxidative stress in chronically glucose-fed rats. Am. J. Hypertens. (2006) 19:407-412.
  • UNGER RH: Lipotoxic diseases. Ann. Rev. Med. (2002) 53:319-336.
  • UNGER R: Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Diabetes (1995) 44:863-870.
  • MCGAVOCK JM, VICTOR RG, UNGER RH, SZCZEPANIAK LS: Adiposity of the heart, revisited. Ann. Intern. Med. (2006) 144:517-524.
  • ZHOU YT, GRAYBURN P, KARIM A et al.: Lipotoxic heart disease in obese rats: implications for human obesity. Proc. Natl. Acad. Sci. USA (2000) 97:1784-1789.
  • PARADISE NF, PILATI CF, PAYNE WR, FINKELSTEIN JA: Left ventricular function of the isolated, genetically obese rat’s heart. Am. J. Physiol. (1985) 248:H438-H444.
  • CHIU HC, KOVACS A, FORD DA et al.: A novel mouse model of lipotoxic cardiomyopathy. J. Clin. Invest. (2001) 107:813-822.
  • LEE Y, NASEEM RH, DUPLOMB L et al.: Hyperleptinemia prevents lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice. Proc. Natl. Acad. Sci. USA (2004) 101:13624-13629.
  • LEE Y, NASEEM RH, PARK BH et al.: α-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice. Biochem. Biophys. Res. Commun. (2006) 344:446-452.
  • HUSS JM, KELLY DP: Nuclear receptor signaling and cardiac energetics. Circ. Res. (2004) 95:568-578.
  • CLARK JM: The epidemiology of nonalcoholic fatty liver disease in adults. J. Clin. Gastroenterol. (2006) 40:S5-S10.
  • FRANZESE A, VAJRO P, ARGENZIANO A et al.: Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosing and during follow-up in an Italian population. Dig. Dis. Sci. (1997) 42:1438-1442.
  • MALNICK SDH, BEERGABEL M, KNOBLER H: Non-alcoholic fatty liver: a common manifestation of a metabolic disorder. QJ Med. (2003) 96:699-709.
  • MARCHESINI G, BUGIANESI E, FORLANI G et al.: Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology (2003) 37:917-923.
  • TRAPPOLIERE M, TUCCILLO C, FEDERICO A et al.: The treatment of NAFLD. Eur. Rev. Med. Pharmacol. Sci. (2005) 9:299-304.
  • ECKEL RH, GRUNDY SM, ZIMMET PZ: The metabolic syndrome. Lancet (2005) 365:1415-1428.
  • ALBERTI KG, ZIMMET P, SHAW J: IDF Epidemiology Task Force Consensus Group. The metabolic syndrome – a new worldwide definition. Lancet (2005) 366:1059-1062.
  • State-specific prevalence of obesity among adults – United States, 2005. MMWR (2006) 55:985-988.
  • THIRUNAVUKKARASU V, ANITHA NANDHINI AT, ANURADHA CV: Lipoic acid attenuates hypertension and improves insulin sensitivity, kallikrein activity and nitrite levels in high fructose-fed rats. J. Comp. Physiol. (B) (2004) 174:587-592.
  • VASDEV S, FORD CA, PARAI S et al.: Dietary lipoic acid supplementation prevents fructose-induced hypertension in rats. Nutr. Metab. Cardiovasc. Dis. (2000) 10:339-346.
  • VASDEV S, GILL V, LONGERICH L et al.: Salt-induced hypertension in WKY rats: prevention by α-lipoic acid supplementation. Mol. Cell. Biochem. (2003) 254:319-326.
  • VASDEV S, FORD CA, PARAI S et al.: Dietary α-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats. J. Hypertens. (2000) 18:567-573.
  • LEE WJ, LEE IK, KIM HS et al.: α-Lipoic acid prevents endothelial dysfunction in obese rats via activation of AMP-activated protein kinase. Arterioscler. Thromb. Vasc. Biol. (2005) 25:2488-2494.
  • LEE KM, PARK KG, KIM YD et al.: α-Lipoic acid inhibits fractalkine expression and prevents neointimal hyperplasia after balloon injury in rat carotid artery. Atherosclerosis (2006) 189:106-114.
  • DE CHAMPLAIN J, WU R, GIROUARD H et al.: Oxidative stress in hypertension. Clin. Exp. Hypertens. (2004) 26:593-601.
  • CHO KJ, MOON HE, MOINI H, PACKER L, YOON DY, CHUNG AS: α-Lipoic acid inhibits adipocyte differentiation by regulating pro-adipogenic transcription factors via mitogen-activated protein kinase pathways. J. Biol. Chem. (2003) 278:34823-34833.
  • BERGER JP, PETRO AE, MACNAUL KL et al.: Distinct properties and advantages of a novel peroxisome proliferator-activated protein γ selective modulator. Mol. Endocrinol. (2003) 17:662-676.
  • TEICHERT J, HERMANN R, RUUS P, PREISS R: Plasma kinetics, metabolism, and urinary excretion of α-lipoic acid following oral administration in healthy volunteers. J. Clin. Pharmacol. (2003) 43:1257-1267.
  • STREEPER RS, HENRIKSEN EJ, JACOB S, HOKAMA JY, FOGT DL, TRITSCHLER HJ: Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. Am. J. Physiol. Endocrinol. Metab. (1997) 273:E185-E191.
  • DEBRIL MB, RENAUD JP, FAJAS L, AUWERX J: The pleiotropic functions of peroxisome proliferator-activated receptor-γ. J. Mol. Med. (2001) 79:30-47.
  • DELERIVE P, FRUCHART JC, STAELS B: Peroxisome proliferator-activated receptors in inflammation control. J. Endocrinol. (2001) 169:453-459.
  • PERSHADSINGH HA: Peroxisome proliferator-activated receptor-γ: therapeutic target for diseases beyond diabetes: quo vadis? Expert Opin. Investig. Drugs (2004) 13(3):215-228.
  • KOSTADINOVA R, WAHLI W, MICHALIK L: PPARs in diseases: control mechanisms of inflammation. Curr. Med. Chem. (2005) 12:2995-3009.
  • BILSKA A, WLODEK L: Lipoic acid – the drug of the future? Pharmacol. Rep. (2005) 57:570-577.
  • HOLMQUIST L, STUCHBURY G, BERBAUM K et al.: Lipoic acid as a novel treatment for Alzheimer’s disease and related dementias. Pharmacol. Ther. (2007) 113(1):154-164.
  • PACKER L, KRAEMER K, RIMBACH G: Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition (2001) 17:888-895.
  • ZIEGLER D: Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat. Endocrinol. (2004) 3:173-189.
  • KOWLURU RA: Diabetic retinopathy: mitochondrial dysfunction and retinal capillary cell death. Antioxid. Redox Signal. (2005) 7:1581-1587.
  • BUSTAMANTE J, LODGE JK, MARCOCCI L, TRITSCHLER HJ, PACKER L, RIHN BH: α-lipoic acid in liver metabolism and disease. Free Radic. Biol. Med. (1998) 24:1023-1039.
  • LEHRKE M, LAZAR MA: The many faces of PPARγ. Cell (2005) 123:993-999.
  • SCHNEIDER JG, TOMPKINS C, BLUMENTHAL RS, MORA S: The metabolic syndrome in women. Cardiol. Rev. (2006) 14:286-291.
  • TEEDE HJ, MEYER C, NORMAN RJ: Insulin-sensitisers in the treatment of polycystic ovary syndrome. Expert Opin. Pharmacother. (2005) 6(14):2419-2427.
  • SHARMA ST, NESTLER JE: Prevention of diabetes and cardiovascular disease in women with PCOS: treatment with insulin sensitizers. Best Pract. Res. Clin. Endocrinol. Metab. (2006) 20:245-260.
  • KOLA B, BOSCARO M, RUTTER GA, GROSSMAN AB, KORBONITS M: Expanding role of AMPK in endocrinology. Trends Endocrinol. Metab. (2006) 17:205-215.

Patent

Website

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.