Dube, John Joseph
(2005)
Leptin and Insulin Sensitivity.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
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.
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Details
Item Type: |
University of Pittsburgh ETD
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Status: |
Unpublished |
Creators/Authors: |
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ETD Committee: |
Title | Member | Email Address | Pitt Username | ORCID |
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Committee Chair | Goodpaster, Bret H | | | | Committee Member | Garcia-Ocana, Adolfo | | | | Committee Member | Zhao, Allan Z | | | | Committee Member | Goss, Fredric L | | | |
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Date: |
20 April 2005 |
Date Type: |
Completion |
Defense Date: |
8 April 2005 |
Approval Date: |
20 April 2005 |
Submission Date: |
11 April 2005 |
Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
Institution: |
University of Pittsburgh |
Schools and Programs: |
School of Education > Health, Physical, Recreational Education |
Degree: |
PhD - Doctor of Philosophy |
Thesis Type: |
Doctoral Dissertation |
Refereed: |
Yes |
Uncontrolled Keywords: |
lipid metabolism |
Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-04112005-095658/, etd-04112005-095658 |
Date Deposited: |
10 Nov 2011 19:35 |
Last Modified: |
15 Nov 2016 13:39 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/6980 |
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