Beneficial impact of L-carnitine in liver: a study in a rat model of syndrome X.
The present study was designed to explore whether L-carnitine (CA) regulates insulin signaling and modulates the changes in liver in a well-characterized insulin resistant rat model. Adult male Wistar rats were divided into 4 groups. Groups I and IV animals received starch-based control diet, while groups II and III rats were fed a high fructose-diet (60 g/100 g). Groups III and IV animals additionally received CA (300 mg/kg/day i.p). After a period of 60 days hepatic tyrosine phosphorylation status was determined by assaying protein tyrosine phosphatase (PTP) and protein tyrosine kinase (PTK) activities. Oxidative damage was monitored by immunohistochemical localization of 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT) and dinitrophenol (DNP)-protein adducts. In addition protein kinase C beta II (PKC beta II) expression, propidium iodide staining of isolated hepatocytes and histology of liver tissue were determined to examine liver integrity. Fructose-fed rats displayed reduced insulin action, increased expression of PKC beta II, altered histology, fragmentation of hepatocyte nuclear DNA, and accumulation of oxidatively modified proteins. Simultaneous treatment with CA alleviated the abnormalities associated with fructose feeding. In summary the data suggest that elevated oxidative damage and PKC expression could in part induce insulin resistance and CA has beneficial impact on liver during insulin resistance with modulatory effects at the post-receptor level.
Rajasekar
P
P
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu, India.
Viswanathan
P
P
Anuradha
C V
CV
D000284:Administration, Oral; D000818:Animals; D002331:Carnitine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005632:Fructose / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
D007328:Insulin; D005632:Fructose; D011505:Protein-Tyrosine Kinases; D002331:Carnitine