Leptin-induced increases in skeletal muscle (SkM) insulin sensitivity (IS) are associated with decreases in SkM lipid levels (Buettner et al. Am J Physiol, 278: E563-E569,2000). However, the role of altered lipid metabolism in the beneficial effects of leptin on SkM IS is poorly understood. The current study addressed the effects of hyperleptinemia (HLEP) on acute hyperlipidemia-induced insulin resistance. Control (CONT) male Wistar rats were infused with either saline (CONT-SAL) or lipid (CONT-LIP) for 5h (5ml/kg/h) followed by a hyperinsulinemic-euglycemic clamp (15mU/kg/min insulin). Gucose infusion rates (GIR) were significantly lower in CONT-LIP vs. CONT-SAL (31.9±1.1 vs. 38.5±0.8 mg/kg/min, P=0.004, n=6/group). As previously reported the lipid metabolites diacylglycerol (DAG, 2.8±0.2 vs 2.1±0.3nMol/mg protein) and ceramide (CER, 0.8±0.1 vs 0.5±0.01nMol/mg protein) were elevated, and triglyceride (TG, 27.5±3.4 vs 41.0±5.7mg/mg protein) decreased (all P<0.05), in soleus muscle (SOL) in LIP vs SAL. In contrast to control animals a lipid infusion in HLEP (plasma leptin=57.8 ng/ml for 5 days) had no effect on GIR compared to saline-infused HLEP (43.0±4.1 vs. 43.8±5.1 mg/kg/min, P=0.40, n=6/group). Furthermore, DAG (2.8±0.2 vs 2.3±0.2), CER (1.1±0.1 vs 1.0±0.1), and TG (17.1±4.9 vs 16.0±2.6) levels in SOL were similar in HLEP-LIP and HLEP-SAL (all P>0.10). Fatty acid oxidation in the isolated SOL, acetyl CoA carboxylase phosphorylation (ACC-P), and the expression of the putative fatty acid transporters FAT/CD36 and FABPpm were similar in HLEP vs CONT. However, membrane-associated PKCtheta was decreased in HLEP-LIP compared to CONT-LIP. We conclude that (1) HLEP prevents IR induced by a lipid infusion, (2) HLEP SkM does not accumulate DAG or CER or deplete TG in response to a lipid infusion, (3) altered FAox or FABPpm, FAT/CD36 expression are not likely sufficient to explain the effects of HLEP, and (4) membrane-associated PKCtheta is suppressed following acute hyperlipidemia in hyperleptinemic animals.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04112005-095658 |
| Date | 20 April 2005 |
| Creators | Dube, John Joseph |
| Contributors | Allan Z. Zhao, PhD, Adolfo Garcia-Ocana, PhD, Fredric L. Goss, PhD, Bret H. Goodpaster, PhD |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04112005-095658/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
Page generated in 0.0015 seconds