title: Prevention of high-fat diet-induced muscular lipid accumulation in rats by alpha lipoic acid is not mediated by AMPK activation.
abstract: Skeletal muscle triglyceride accumulation is associated with insulin resistance in obesity. Recently, it has been suggested that alpha lipoic acid (ALA) improves insulin sensitivity by lowering triglyceride accumulation in nonadipose tissues via activation of skeletal muscle AMP-activated protein kinase (AMPK). We examined whether chronic ALA supplementation prevents muscular lipid accumulation that is associated with high-fat diets via activation of AMPK. In addition, we tested if ALA supplementation was able to improve insulin sensitivity in rats fed low- and high-fat diets (LFD, HFD). Supplementing male Wistar rats with 0.5% ALA for 8 weeks significantly reduced body weight, both on LFD and HFD (-24% LFD+ALA vs. LFD, P < 0.01, and -29% HFD+ALA vs. HFD, P < 0.001). Oil red O lipid staining revealed a 3-fold higher lipid content in skeletal muscle after HFD compared with LFD and ALA-supplemented groups (P < 0.05). ALA improved whole body glucose tolerance ( approximately 20% lower total area under the curve (AUC) in ALA supplemented groups vs. controls, P < 0.05). These effects were not mediated by increased muscular AMPK activation or ALA-induced improvement of muscular insulin sensitivity. To conclude, the prevention of HFD-induced muscular lipid accumulation and the improved whole body glucose tolerance are likely secondary effects due to the anorexic nature of ALA.
authors.affiliation: Top Institute Food and Nutrition (TIFN), 6700 AN, Wageningen, The Netherlands.
authors.forename: Silvie
authors.initials: S
authors.lastname: Timmers
authors.forename: Johan
authors.initials: J
authors.lastname: de Vogel-van den Bosch
authors.forename: Mhairi C
authors.initials: MC
authors.lastname: Towler
authors.forename: Gert
authors.initials: G
authors.lastname: Schaart
authors.forename: Esther
authors.initials: E
authors.lastname: Moonen-Kornips
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mensink
authors.forename: Matthijs K
authors.initials: MK
authors.lastname: Hesselink
authors.forename: D Grahame
authors.initials: DG
authors.lastname: Hardie
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000042:Absorption / Q000187:drug effects; D000328:Adult; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000494:pharmacology*; D019587:Dietary Supplements; D004435:Eating / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D008063:Thioctic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004041:Dietary Fats; D007328:Insulin; D008063:Thioctic Acid; D055372:AMP-Activated Protein Kinases; D005947:Glucose
references.citation: J Biol Chem. 2004 Mar 26;279(13):12005-8
references.pmid: 14742438
references.citation: JAMA. 2003 Jan 1;289(1):76-9
references.pmid: 12503980
references.citation: Eur J Biochem. 1989 Dec 8;186(1-2):123-8
references.pmid: 2574667
references.citation: Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):15983-7
references.pmid: 12444247
references.citation: Free Radic Biol Med. 1999 Aug;27(3-4):309-14
references.pmid: 10468203
references.citation: Nature. 2004 Apr 1;428(6982):569-74
references.pmid: 15058305
references.citation: FASEB J. 2003 Dec;17(15):2272-4
references.pmid: 14525936
references.citation: Diabetes. 1996 Aug;45(8):1024-9
references.pmid: 8690147
references.citation: J Biol Chem. 2001 Oct 19;276(42):38329-36
references.pmid: 11477096
references.citation: Free Radic Biol Med. 1995 Aug;19(2):227-50
references.pmid: 7649494
references.citation: Diabetes. 1996 Dec;45(12):1798-804
references.pmid: 8922368
references.citation: Diabetes Res Clin Pract. 1995 Feb;27(2):97-106
references.pmid: 7607057
references.citation: Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2412-21
references.pmid: 15637122
references.citation: Am J Physiol. 1999 Jan;276(1):E1-E18
references.pmid: 9886945
references.citation: Exp Clin Endocrinol Diabetes. 1996;104(3):284-8
references.pmid: 8817248
references.citation: Diabetes Obes Metab. 2002 Jan;4(1):29-35
references.pmid: 11874439
references.citation: Eur J Biochem. 1997 Jun 1;246(2):259-73
references.pmid: 9208914
references.citation: J Cell Biol. 1993 May;121(4):795-810
references.pmid: 8491773
references.citation: Methods Enzymol. 1979;62:152-8
references.pmid: 374970
references.citation: Biochem Biophys Res Commun. 2005 Jul 8;332(3):885-91
references.pmid: 15913551
references.citation: J Appl Physiol (1985). 2001 Sep;91(3):1017-28
references.pmid: 11509493
references.citation: J Appl Physiol (1985). 2009 Apr;106(4):1425-34
references.pmid: 19179648
references.citation: Diabetes. 2000 Apr;49(4):527-31
references.pmid: 10871188
references.citation: Arch Biochem Biophys. 1974 Feb;160(2):514-22
references.pmid: 4598618
references.citation: J Clin Invest. 1999 Jan;103(2):253-9
references.pmid: 9916137
references.citation: Biochem Biophys Res Commun. 2005 Jan 7;326(1):197-202
references.pmid: 15567171
references.citation: Am J Physiol Endocrinol Metab. 2001 Dec;281(6):E1340-6
references.pmid: 11701451
references.citation: Free Radic Biol Med. 1998 Apr;24(6):1023-39
references.pmid: 9607614
references.citation: Clin Sci (Lond). 2009 Jan;116(2):113-23
references.pmid: 19076064
references.citation: Arch Biochem Biophys. 2005 Apr 15;436(2):276-84
references.pmid: 15797240
references.citation: Biochem Soc Symp. 2004;(71):203-13
references.pmid: 15777023
references.citation: Nat Med. 2004 Jul;10(7):727-33
references.pmid: 15195087