Lipotoxicity: the obese and endurance-trained paradox

Russell, Aaron 2004, Lipotoxicity: the obese and endurance-trained paradox, International journal of obesity, vol. 28, pp. S66-S71, doi: 10.1038/sj.ijo.0802859.

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Title Lipotoxicity: the obese and endurance-trained paradox
Author(s) Russell, AaronORCID iD for Russell, Aaron
Journal name International journal of obesity
Volume number 28
Start page S66
End page S71
Publisher Nature Publishing Group
Place of publication London, England
Publication date 2004
ISSN 0307-0565
Keyword(s) intramyocellular triglycerides
insulin resistance
signalling pathways
Summary The potential lipotoxic effect of intramyocellular triglyceride (IMTG) accumulation has been suggested to be a major component in the development of insulin resistance. Increased levels of IMTGs correlate with insulin resistance in both obese and diabetic patients, but this relationship does not exist in endurance trained (ETr) subjects. This may be, in part, related to differences in the gene expression and activities of key enzymes involved in fatty acid transport and oxidation as well as in the perodixation status of the IMTGs in obese/diabetic patients as compared with ETr subjects. Disruptions in fat and lipid homeostasis in skeletal muscle have been shown to activate protein kinase C (PKC), which acts on several downstream signalling pathways, including the insulin and the IB kinase (IKK)/NFB signalling pathways. Additionally, an increased peroxidation of IMTGs may reduce insulin sensitivity by increasing TNF, which is known to increase the expression of suppressor of cytokine signalling proteins (SOCS). A common characteristic observed when activating both PKC and TNF/SOCS3 is the inhibition of tyrosine phosphorylation of IRS-1 and subsequently an inhibition of its activation of downstream signalling molecules. These may be important players in the development of insulin resistance and understanding their activation and expression in both obese and ETr humans should assist in understanding how and why IMTGs become lipotoxic.

Language eng
DOI 10.1038/sj.ijo.0802859
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2004, Nature Publishing Group
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