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Mechanisms by which lipoic acid prevents high fat diet‐induced insulin resistance in skeletal muscle.
Author(s) -
Gupte Anisha A,
Bomhoff Gregory L.,
Morris Jill K.,
Gorres Brittany K.,
Geiger Paige C.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.958.9
Subject(s) - medicine , endocrinology , insulin resistance , insulin , ampk , protein kinase b , skeletal muscle , insulin receptor , p38 mitogen activated protein kinases , glucose uptake , glucose transporter , amp activated protein kinase , hsp70 , protein kinase a , kinase , chemistry , biology , signal transduction , heat shock protein , biochemistry , gene
High fat diet‐induced insulin resistance is associated with impaired insulin signal transduction and reduced glucose transport in skeletal muscle. The anti‐oxidant alpha‐lipoic acid (LA) has been shown to improve insulin action in high fat fed animal models, yet little is known about the underlying mechanism. We hypothesize that LA acts by directly inhibiting stress kinases, such as c‐Jun N‐terminal kinase (JNK), known to interfere with insulin signaling intermediates. Male Wistar rats were fed a high fat diet (HFD, 60% calories from fat) for six weeks, while controls received a low fat diet (20% calories from fat). Half of the rats in each group received daily LA injections (30 mg/kg body wt). LA increased whole body glucose disposal in both diet groups as measured by oral glucose tolerance tests. LA treatment effectively restored insulin responsiveness in soleus muscles from rats fed a HFD, as seen by insulin‐stimulated pAkt/Akt and 2‐deoxyglucose uptake. LA treatment reduced the elevation of JNK (pJNK/JNK) seen with the HFD and increased activation of p38 MAPK and AMPK (pAMPK/AMPK), a mediator of insulin independent glucose transport. In addition, LA increased expression of heat shock protein 70 (HSP70), a protein previously shown to directly inhibit JNK activation, in rats fed a HFD. In conclusion, LA reversed HFD induced insulin resistance by reducing JNK, and increasing p38 MAPK, AMPK and HSP70 activation.