SHORT-TERM ALTERATIONS IN CARBOHYDRATE ENERGY-INTAKE IN HUMANS - STRIKING EFFECTS ON HEPATIC GLUCOSE-PRODUCTION, DE-NOVO LIPOGENESIS, LIPOLYSIS, AND WHOLE-BODY FUEL SELECTION

Short-term alterations in dietary carbohydrate (CHO) energy are known to alter whole-body fuel selection in humans, but the metabolic mechan isms remain unknown, We used stable isotope-mass spectrometric methods with indirect calorimetry in normal subjects to quantify the metaboli c response to six dietary phases (5 d each), ranging from 50% surplus CHO (+50% CHO) to 50% deficient CHO (-50% CHO), and 50% surplus fat (/-50% fat), Pasting hepatic glucose production (HGP) varied by > 40% f rom deficient to surplus CHO diets (1.78+/-0.08 vs 2.43+/-0.09 mg/kg p er min, P < 0.01). Increased HGP on surplus CHO occurred despite signi ficantly higher serum insulin concentrations. Lipolysis correlated inv ersely with CHO intake as did the proportion of whole-body lipolytic f lux oxidized, Fractional de novo hepatic lipogenesis (DNL) increased m ore than 10-fold on surplus CHO and was unmeasurable on deficient CHO diets; thus, the preceding 5-d CHO intake could be inferred from DNL, Nevertheless, absolute hepatic DNL accounted for < 5 g fatty acids syn thesized per day even on +50% CHO, Whole-body CHO oxidation increased sixfold and fat oxidation decreased > 90% on surplus CHO diets, CHO ox idation was highly correlated with HGP (r(2) = 0.60), HGP could accoun t for 85% of fasting CHO oxidation on +25% CHO and 67% on +50% CHO die ts, Some oxidation of intracellular CHO stores was therefore also occu rring, +50% fat diet had no effects on HGP, DNL, or fuel selection. We conclude that altered CHO intake alters HGP specifically and in a dos e-dependent manner, that HGP may mediate the effects of CHO on whole-b ody fuel selection both by providing substrate and by altering serum i nsulin concentrations, that altered lipolysis and tissue oxidation eff iciency contribute to changes in fat oxidation, and that surplus CHO i s not substantially converted by the liver to fat as it spares fat oxi dation, but that fractional DNL may nevertheless be a qualitative mark er of recent CHO intake.