Prevention of high-fat diet-induced muscular lipid accumulation in rats by alpha lipoic acid is not mediated by AMPK activation.
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.
Timmers
Silvie
S
Top Institute Food and Nutrition (TIFN), 6700 AN, Wageningen, The Netherlands.
de Vogel-van den Bosch
Johan
J
Towler
Mhairi C
MC
Schaart
Gert
G
Moonen-Kornips
Esther
E
Mensink
Ronald P
RP
Hesselink
Matthijs K
MK
Hardie
D Grahame
DG
Schrauwen
Patrick
P
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*
D004041:Dietary Fats; D007328:Insulin; D008063:Thioctic Acid; D055372:AMP-Activated Protein Kinases; D005947:Glucose
J Biol Chem. 2004 Mar 26;279(13):12005-8
14742438
JAMA. 2003 Jan 1;289(1):76-9
12503980
Eur J Biochem. 1989 Dec 8;186(1-2):123-8
2574667
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):15983-7
12444247
Free Radic Biol Med. 1999 Aug;27(3-4):309-14
10468203
Nature. 2004 Apr 1;428(6982):569-74
15058305
FASEB J. 2003 Dec;17(15):2272-4
14525936
Diabetes. 1996 Aug;45(8):1024-9
8690147
J Biol Chem. 2001 Oct 19;276(42):38329-36
11477096
Free Radic Biol Med. 1995 Aug;19(2):227-50
7649494
Diabetes. 1996 Dec;45(12):1798-804
8922368
Diabetes Res Clin Pract. 1995 Feb;27(2):97-106
7607057
Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2412-21
15637122
Am J Physiol. 1999 Jan;276(1):E1-E18
9886945
Exp Clin Endocrinol Diabetes. 1996;104(3):284-8
8817248
Diabetes Obes Metab. 2002 Jan;4(1):29-35
11874439
Eur J Biochem. 1997 Jun 1;246(2):259-73
9208914
J Cell Biol. 1993 May;121(4):795-810
8491773
Methods Enzymol. 1979;62:152-8
374970
Biochem Biophys Res Commun. 2005 Jul 8;332(3):885-91
15913551
J Appl Physiol (1985). 2001 Sep;91(3):1017-28
11509493
J Appl Physiol (1985). 2009 Apr;106(4):1425-34
19179648
Diabetes. 2000 Apr;49(4):527-31
10871188
Arch Biochem Biophys. 1974 Feb;160(2):514-22
4598618
J Clin Invest. 1999 Jan;103(2):253-9
9916137
Biochem Biophys Res Commun. 2005 Jan 7;326(1):197-202
15567171
Am J Physiol Endocrinol Metab. 2001 Dec;281(6):E1340-6
11701451
Free Radic Biol Med. 1998 Apr;24(6):1023-39
9607614
Clin Sci (Lond). 2009 Jan;116(2):113-23
19076064
Arch Biochem Biophys. 2005 Apr 15;436(2):276-84
15797240
Biochem Soc Symp. 2004;(71):203-13
15777023
Nat Med. 2004 Jul;10(7):727-33
15195087