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Basic Science| Volume 62, ISSUE 1, P44-51, January 2013

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Acute hyperinsulinemia and reduced plasma free fatty acid levels decrease intramuscular triglyceride synthesis

  • Xiao-jun Zhang
    Affiliations
    Metabolism Unit, Shriners Hospital for Children, University of Texas Medical Branch, Galveston, TX 77550, USA

    Department of Surgery, University of Texas Medical Branch, Galveston, TX 77550, USA
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  • Lijian Wang
    Affiliations
    Metabolism Unit, Shriners Hospital for Children, University of Texas Medical Branch, Galveston, TX 77550, USA

    Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77550, USA
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  • Demidmaa Tuvdendorj
    Affiliations
    Metabolism Unit, Shriners Hospital for Children, University of Texas Medical Branch, Galveston, TX 77550, USA

    Department of Surgery, University of Texas Medical Branch, Galveston, TX 77550, USA
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  • Zhanpin Wu
    Affiliations
    Metabolism Unit, Shriners Hospital for Children, University of Texas Medical Branch, Galveston, TX 77550, USA

    Department of Surgery, University of Texas Medical Branch, Galveston, TX 77550, USA
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  • Noe A. Rodriguez
    Affiliations
    Metabolism Unit, Shriners Hospital for Children, University of Texas Medical Branch, Galveston, TX 77550, USA

    Department of Surgery, University of Texas Medical Branch, Galveston, TX 77550, USA
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  • David N. Herndon
    Affiliations
    Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77550, USA
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  • Robert R. Wolfe
    Correspondence
    Corresponding author. Tel.: +1 501 526 5709; fax: +1 501 686 8025.
    Affiliations
    University of Arkansas for Medical Sciences, Geriatrics, 4301 West Markham Street, Slot 806, Little Rock, AR 72205–7199, USA
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      Abstract

      Objective

      To investigate the effect of acute hyperinsulinemia and the resulting decrease in plasma free fatty acid (FFA) concentrations on intramuscular TG synthesis.

      Materials/Methods

      U-13C16-palmitate was infused for 3 h in anesthetized rabbits after overnight food deprivation. Arterial blood and leg muscle were sampled during the tracer infusion. Plasma samples were analyzed for free and TG-bound palmitate enrichments and concentrations. The enrichments and concentrations of palmitoyl-CoA and palmitoyl-carnitine as well as the enrichment of palmitate bound to TG were measured in muscle samples. Fractional synthetic rate (FSR) of intramuscular TG was calculated using the tracer incorporation method. The rabbits were divided into a control group and a hyperinsulinemic euglycemic clamp group. Insulin infusion decreased the rate of appearance of plasma free palmitate (2.00±0.15 vs 0.68±0.20 μmol⋅kg−1min−1; P<.001), decreased plasma FFA concentration (327±61 vs 72±25 nmol/mL; P<.01), decreased the total concentration of intramuscular fatty acyl-CoA plus fatty acyl-carnitine (12.1±1.6 vs 7.0±0.7 nmol/g; P<.05), and decreased intramuscular TG FSR (0.48±0.05 vs 0.21±0.06%/h; P<.01) in comparison with the control group. Intramuscular TG FSR was correlated (P<.01) with both plasma FFA concentrations and intramuscular fatty acyl-CoA concentrations.

      Conclusions

      Fatty acid availability is a determinant of intramuscular TG synthesis. Insulin infusion decreases plasma and intramuscular fatty acid availability and thereby decreases TG synthesis.

      Abbreviations:

      IM (intramuscular), TG (triglyceride), FFA (free fatty acid(s)), CoA (coenzyme A), PalCoA (palmitoyl-CoA), PalCn (palmitoyl-carnitine), PL (phospholipids(s)), FSR (fractional synthetic rate(s)), GC-MS (gas chromatograph-mass spectrometer)

      Keywords

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      References

        • DeFronzo R.A.
        • Jacot E.
        • Jequier E.
        • et al.
        The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization.
        Diabetes. 1981; 30: 1000-1007
        • Shulman G.I.
        • Rothman D.L.
        • Jue T.
        • et al.
        Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscope.
        N Eng J Med. 1990; 322: 223-228
        • Cahova M.
        • Vavrinkova H.
        • Kazdova L.
        Glucose–fatty acid interaction in skeletal muscle and adipose tissue in insulin resistance.
        Physiol Res. 2007; 56: 1-15
        • Pan D.A.
        • Lillioja S.
        • Kriketos A.D.
        • et al.
        Skeletal muscle triglyceride levels are inversely related to insulin action.
        Diabetes. 1997; 46: 983-988
        • Cooney G.J.
        • Thompson A.L.
        • Furler S.M.
        • et al.
        Muscle long-chain acyl-CoA esters and insulin resistance.
        Ann N Y Acad Sci. 2002; 967: 196-207
        • Boden G.
        Ceramide: a contributor to insulin resistance or an innocent bystander?.
        Diabetologia. 2008; 51: 1095-1096
        • Timmers S.
        • Schrauwen P.
        • de Vogel J.
        Muscular diacylglycerol metabolism and insulin resistance.
        Physiol Behav. 2008; 94: 242-251
        • Schenk S.
        • Horowitz J.F.
        Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid induced insulin resistance.
        J Clin Invest. 2007; 117: 1690-1698
        • Goodpaster B.H.
        • He J.
        • Watkins S.
        • et al.
        Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes.
        J Clin Endocrinol Meatb. 2001; 86: 5755-5761
        • Boden G.
        Role of fatty acids in the pathogenesis of insulin resistance and NIDDM.
        Diabetes. 1997; 46: 3-10
        • Boden G.
        • Lebed B.
        • Schatz M.
        • et al.
        Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects.
        Diabetes. 2002; 50: 1612-1617
        • Bergman B.C.
        • Perreault L.
        • Hunderdosse D.M.
        • et al.
        Increased intramuscular lipid synthesis and low saturation relate to insulin sensitivity in endurance-trained athletes.
        J Apply Physiol. 2010; 108: 1134-1141
        • Bergman B.C.
        • Perreault L.
        • Hunerdosse D.M.
        • et al.
        Intramuscular lipid metabolism in the insulin resistance of smoking.
        Diabetes. 2009; 58: 2220-2227
        • Perreault L.
        • Bergman B.C.
        • Hunerdosse D.M.
        • et al.
        Altered intramuscular lipid metabolism relates to diminished insulin action in men, but not women, in progression to diabetes.
        Obesity. 2010; 18: 2093-2100
        • Guo Z.
        • Jensen M.D.
        Intramuscular fatty acid metabolism evaluated with stable isotopic tracers.
        J Appl Physiol. 1998; 84: 1674-1679
        • Sacchetti M.
        • Saltin B.
        • Olsen D.B.
        • et al.
        High triacylglycerol turnover rate in human skeletal muscle.
        J Physiol. 2004; 561.3: 883-891
        • X-j Zhang
        • Rodriguez N.A.
        • Wang L.
        • et al.
        Measurement of precursor enrichment for calculating intramuscular triglyceride fractional synthetic rate.
        J Lipid Res. 2012; 53: 119-125
        • Zhang X.-J.
        • Chinkes D.L.
        • Wu Z.
        • et al.
        The synthetic rate of muscle triglyceride but not phospholipids is increased in obese rabbits in comparison with lean rabbits.
        Metabolism. 2009; 58: 1649-1656
        • Guo Z.
        • Zhou L.
        • Jensen M.D.
        Acute hyperinsulinemia inhibits intramyocellular triglyceride synthesis in high-fat-fed obese rats.
        J Lipid Res. 2006; 47: 2640-2646
        • Boden G.
        • Lebed B.
        • Schatz M.
        • et al.
        Effects of acute changes of plasma free fatty acids on intramylcellular fat content and insulin resistance in healthy subjects.
        Diabetes. 2002; 50: 1612-1617
        • Sun D.
        • Cree M.G.
        • Wolfe R.R.
        Quantification of the concentration and 13C tracer enrichment of long-chain fatty acyl-coenzyme A in muscle by liquid chromatography/mass spectrometry.
        Analytic Biochem. 2006; 349: 87-95
        • Sun D.
        • Cree M.G.
        • Zhang X.-J.
        • et al.
        Measurement of stable isotopic enrichment and concentration of long-chain fatty acyl-carnitines in tissue by HPLC-MS.
        J Lipid Res. 2006; 47: 431-439
        • Wolfe R.R.
        • Chinkes D.L.
        Isotopic tracers in metabolic research: principle and practice of kinetic analysis. 2nd ed. Wiley-Liss, New Jersey2004: 325-360
        • Romijn J.A.
        • Coyle E.F.
        • Sidossis L.
        • et al.
        Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration.
        Am J Physiol. 1993; 265: E380-E391
        • Guo Z.
        • Zhou L.
        Fatty acids inhibit intramyocellular triglyceride synthesis and turnover acutely in high fat-fed obese rats.
        Horm Metab Res. 2006; 38: 721-726
        • Price E.R.
        • Guglielmo C.G.
        The effect of muscle phospholipid fatty acid composition on exercise performance: a direct test in the migratory white-throated sparrow.
        Am J Physiol. 2009; 297: R775-R782
        • Zammit P.S.
        • Partridge T.A.
        • Yablonka-Reuveni Z.
        The skeletal muscle satellite cell: the stem cell that come in from the cold.
        J Histochem Cytochem. 2006; 54: 1177-1191
        • Zhang X.-J.
        • Chinkes D.L.
        • Irtun O.
        • et al.
        Anabolic action of insulin on skin wound protein is augmented by exogenous amino acids.
        Am J Physiol. 2002; 282: E1308-E1315
        • Randle P.J.
        • Garland P.B.
        • Hales C.N.
        • et al.
        The glucose–fatty acid cycle: its role in insulin sensitivity and metabolic disturbances of diabetes mellitus.
        Lancet. 1963; : 785-789