Lipid-dependent control of hepatic glycogen stores in healthy humans

Aims/hypothesis. Non-esterified fatty acids and glycerol could stimulate gl uconeogenesis and also contribute to regulating hepatic glycogen stores. We examined their effect on liver glycogen breakdown in humans. Methods. After an overnight fast healthy subjects participated in three pro tocols with lipid/heparin (plasma non-esterified fatty acids: 2.2 +/- 0.1 m ol/l; plasma glycerol: 0.5 +/- 0.03mol/l; n=7), glycerol (0.4 +/- 0.1 mol/l ; 1.5 +/- 0.2 mol/l; n = 5) and saline infusion (control; 0.5 +/- 0.1 mol/l ; 0.2 rt 0.02 mol/l; n = 7). Net rates of glycogen breakdown were calculate d from the decrease of liver glycogen within 9 h using C-13 nuclear magneti c resonance spectroscopy. Endogenous glucose production was measured with i nfusion of D-[6,6-H-2(2)]glucose, Results. Endogenous glucose production decreased by about 25 % during lipid and saline infusion (p < 0.005) but not during glycerol infusion (p < 0.00 1 vs lipid, saline). An increase of plasma non-esterified fatty acids or gl ycerol reduced the net glycogen breakdown by about 84 % to 0.6 +/- 0.3 mu m ol.kg(-1) min(-1) (p < 0.001 vs saline: 3.7 +/- 0.5 <mu>mol.kg(-1) min(-1)) and by about 46 % to 2.0 +/- 0.4 mu mol.kg(-1) min(-1) (p < 0.01 vs saline and lipid), respectively. Rates of gluconeogenesis increased to 11.5 +/- 0 .8 <mu>mol.kg(-1) min(-1) (p < 0.01) and 12.8 +/- 1.0 <mu>mol.kg(-1).min(-1 ) (p < 0.01 vs saline: 8.2 +/- 0.7 <mu>mol.1(-1).min(-1)), respectively. Conclusion/interpretation: An increase of non-esterified fatty acid leads t o a pronounced inhibition of net hepatic glycogen breakdown and increases g luconeogenesis whereas glucose production does not differ from the control condition. We suggest that this effect is not due to increased availability of glycerol alone but rather to lipid-dependent control of hepatic glycoge n stores.