Abstract
Short-term alterations in dietary carbohydrate (CHO) energy are known to alter whole-body fuel selection in humans, but the metabolic mechanisms remain unknown. We used stable isotope-mass spectrometric methods with indirect calorimetry in normal subjects to quantify the metabolic 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). Fasting hepatic glucose production (HGP) varied by > 40% from deficient to surplus CHO diets (1.78 +/- 0.08 vs 2.43 +/- 0.09 mg/kg per min, P < 0.01). Increased HGP on surplus CHO occurred despite significantly higher serum insulin concentrations. Lipolysis correlated inversely with CHO intake as did the proportion of whole-body lipolytic flux oxidized. Fractional de novo hepatic lipogenesis (DNL) increased more 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 < 5g fatty acids synthesized per day even on +50% CHO. Whole-body CHO oxidation increased sixfold and fat oxidation decreased > 90% on surplus CHO diets. CHO oxidation was highly correlated with HGP (r2= 0.60). HGP could account for 85% of fasting CHO oxidation on +25% CHO and 67% on +50% CHO diets. Some oxidation of intracellular CHO stores was therefore also occurring. +50% fat diet had no effects on HGP, DNL, or fuel selection. We conclude that altered CHO intake alters HGP specifically and in a dose-dependent manner, that HGP may mediate the effects of CHO on whole-body fuel selection both by providing substrate and by altering serum insulin concentrations, that altered lipolysis and tissue oxidation efficiency contribute to changes in fat oxidation, and that surplus CHO is not substantially converted by the liver to fat as it spares fat oxidation, but that fractional DNL may nevertheless be a qualitative marker of recent CHO intake.
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- Acheson K. J., Schutz Y., Bessard T., Ravussin E., Jéquier E., Flatt J. P. Nutritional influences on lipogenesis and thermogenesis after a carbohydrate meal. Am J Physiol. 1984 Jan;246(1 Pt 1):E62–E70. doi: 10.1152/ajpendo.1984.246.1.E62. [DOI] [PubMed] [Google Scholar]
- Astrup A., Raben A. Obesity: an inherited metabolic deficiency in the control of macronutrient balance? Eur J Clin Nutr. 1992 Sep;46(9):611–620. [PubMed] [Google Scholar]
- BIERMAN E. L., DOLE V. P., ROBERTS T. N. An abnormality of nonesterified fatty acid metabolism in diabetes mellitus. Diabetes. 1957 Nov-Dec;6(6):475–479. doi: 10.2337/diab.6.6.475. [DOI] [PubMed] [Google Scholar]
- Bandini L. G., Schoeller D. A., Edwards J., Young V. R., Oh S. H., Dietz W. H. Energy expenditure during carbohydrate overfeeding in obese and nonobese adolescents. Am J Physiol. 1989 Mar;256(3 Pt 1):E357–E367. doi: 10.1152/ajpendo.1989.256.3.E357. [DOI] [PubMed] [Google Scholar]
- Cahill G. F., Jr Starvation in man. Clin Endocrinol Metab. 1976 Jul;5(2):397–415. doi: 10.1016/s0300-595x(76)80028-x. [DOI] [PubMed] [Google Scholar]
- Cavalieri R. R. The effects of nonthyroid disease and drugs on thyroid function tests. Med Clin North Am. 1991 Jan;75(1):27–39. doi: 10.1016/s0025-7125(16)30470-9. [DOI] [PubMed] [Google Scholar]
- DeFronzo R. A., Simonson D., Ferrannini E. Hepatic and peripheral insulin resistance: a common feature of type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1982 Oct;23(4):313–319. doi: 10.1007/BF00253736. [DOI] [PubMed] [Google Scholar]
- Ferrannini E. The theoretical bases of indirect calorimetry: a review. Metabolism. 1988 Mar;37(3):287–301. doi: 10.1016/0026-0495(88)90110-2. [DOI] [PubMed] [Google Scholar]
- Flatt J. P. Dietary fat, carbohydrate balance, and weight maintenance: effects of exercise. Am J Clin Nutr. 1987 Jan;45(1 Suppl):296–306. doi: 10.1093/ajcn/45.1.296. [DOI] [PubMed] [Google Scholar]
- Féry F. Role of hepatic glucose production and glucose uptake in the pathogenesis of fasting hyperglycemia in type 2 diabetes: normalization of glucose kinetics by short-term fasting. J Clin Endocrinol Metab. 1994 Mar;78(3):536–542. doi: 10.1210/jcem.78.3.8126123. [DOI] [PubMed] [Google Scholar]
- Groop L. C., Bonadonna R. C., DelPrato S., Ratheiser K., Zyck K., Ferrannini E., DeFronzo R. A. Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. J Clin Invest. 1989 Jul;84(1):205–213. doi: 10.1172/JCI114142. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartman M. L., Veldhuis J. D., Johnson M. L., Lee M. M., Alberti K. G., Samojlik E., Thorner M. O. Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men. J Clin Endocrinol Metab. 1992 Apr;74(4):757–765. doi: 10.1210/jcem.74.4.1548337. [DOI] [PubMed] [Google Scholar]
- Hellerstein M. K., Benowitz N. L., Neese R. A., Schwartz J. M., Hoh R., Jacob P., 3rd, Hsieh J., Faix D. Effects of cigarette smoking and its cessation on lipid metabolism and energy expenditure in heavy smokers. J Clin Invest. 1994 Jan;93(1):265–272. doi: 10.1172/JCI116955. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hellerstein M. K., Christiansen M., Kaempfer S., Kletke C., Wu K., Reid J. S., Mulligan K., Hellerstein N. S., Shackleton C. H. Measurement of de novo hepatic lipogenesis in humans using stable isotopes. J Clin Invest. 1991 May;87(5):1841–1852. doi: 10.1172/JCI115206. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hellerstein M. K., Grunfeld C., Wu K., Christiansen M., Kaempfer S., Kletke C., Shackleton C. H. Increased de novo hepatic lipogenesis in human immunodeficiency virus infection. J Clin Endocrinol Metab. 1993 Mar;76(3):559–565. doi: 10.1210/jcem.76.3.8445011. [DOI] [PubMed] [Google Scholar]
- Hellerstein M. K., Neese R. A. Mass isotopomer distribution analysis: a technique for measuring biosynthesis and turnover of polymers. Am J Physiol. 1992 Nov;263(5 Pt 1):E988–1001. doi: 10.1152/ajpendo.1992.263.5.E988. [DOI] [PubMed] [Google Scholar]
- Hellerstein M. K., Wu K., Kaempfer S., Kletke C., Shackleton C. H. Sampling the lipogenic hepatic acetyl-CoA pool in vivo in the rat. Comparison of xenobiotic probe to values predicted from isotopomeric distribution in circulating lipids and measurement of lipogenesis and acetyl-CoA dilution. J Biol Chem. 1991 Jun 15;266(17):10912–10919. [PubMed] [Google Scholar]
- Henry R. R., Scheaffer L., Olefsky J. M. Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1985 Nov;61(5):917–925. doi: 10.1210/jcem-61-5-917. [DOI] [PubMed] [Google Scholar]
- Hers H. G. The control of glycogen metabolism in the liver. Annu Rev Biochem. 1976;45:167–189. doi: 10.1146/annurev.bi.45.070176.001123. [DOI] [PubMed] [Google Scholar]
- Hill J. O., Peters J. C., Reed G. W., Schlundt D. G., Sharp T., Greene H. L. Nutrient balance in humans: effects of diet composition. Am J Clin Nutr. 1991 Jul;54(1):10–17. doi: 10.1093/ajcn/54.1.10. [DOI] [PubMed] [Google Scholar]
- Jahoor F., Peters E. J., Wolfe R. R. The relationship between gluconeogenic substrate supply and glucose production in humans. Am J Physiol. 1990 Feb;258(2 Pt 1):E288–E296. doi: 10.1152/ajpendo.1990.258.2.E288. [DOI] [PubMed] [Google Scholar]
- Jenssen T., Nurjhan N., Consoli A., Gerich J. E. Failure of substrate-induced gluconeogenesis to increase overall glucose appearance in normal humans. Demonstration of hepatic autoregulation without a change in plasma glucose concentration. J Clin Invest. 1990 Aug;86(2):489–497. doi: 10.1172/JCI114735. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelley D. E., Wing R., Buonocore C., Sturis J., Polonsky K., Fitzsimmons M. Relative effects of calorie restriction and weight loss in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1993 Nov;77(5):1287–1293. doi: 10.1210/jcem.77.5.8077323. [DOI] [PubMed] [Google Scholar]
- Klein S., Wolfe R. R. Carbohydrate restriction regulates the adaptive response to fasting. Am J Physiol. 1992 May;262(5 Pt 1):E631–E636. doi: 10.1152/ajpendo.1992.262.5.E631. [DOI] [PubMed] [Google Scholar]
- McGarry J. D., Foster D. W. Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem. 1980;49:395–420. doi: 10.1146/annurev.bi.49.070180.002143. [DOI] [PubMed] [Google Scholar]
- Neese R. A., Benowitz N. L., Hoh R., Faix D., LaBua A., Pun K., Hellerstein M. K. Metabolic interactions between surplus dietary energy intake and cigarette smoking or its cessation. Am J Physiol. 1994 Dec;267(6 Pt 1):E1023–E1034. doi: 10.1152/ajpendo.1994.267.6.E1023. [DOI] [PubMed] [Google Scholar]
- Oster M. H., Fielder P. J., Levin N., Cronin M. J. Adaptation of the growth hormone and insulin-like growth factor-I axis to chronic and severe calorie or protein malnutrition. J Clin Invest. 1995 May;95(5):2258–2265. doi: 10.1172/JCI117916. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shrago E., Glennon J. A., Gordon E. S. Comparative aspects of lipogenesis in mammalian tissues. Metabolism. 1971 Jan;20(1):54–62. doi: 10.1016/0026-0495(71)90059-x. [DOI] [PubMed] [Google Scholar]
- Thiebaud D., Jacot E., DeFronzo R. A., Maeder E., Jequier E., Felber J. P. The effect of graded doses of insulin on total glucose uptake, glucose oxidation, and glucose storage in man. Diabetes. 1982 Nov;31(11):957–963. doi: 10.2337/diacare.31.11.957. [DOI] [PubMed] [Google Scholar]
- Watts N. B., Spanheimer R. G., DiGirolamo M., Gebhart S. S., Musey V. C., Siddiq Y. K., Phillips L. S. Prediction of glucose response to weight loss in patients with non-insulin-dependent diabetes mellitus. Arch Intern Med. 1990 Apr;150(4):803–806. [PubMed] [Google Scholar]
- Wing R. R., Blair E. H., Bononi P., Marcus M. D., Watanabe R., Bergman R. N. Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients. Diabetes Care. 1994 Jan;17(1):30–36. doi: 10.2337/diacare.17.1.30. [DOI] [PubMed] [Google Scholar]
- Yki-Järvinen H., Bogardus C., Howard B. V. Hyperglycemia stimulates carbohydrate oxidation in humans. Am J Physiol. 1987 Oct;253(4 Pt 1):E376–E382. doi: 10.1152/ajpendo.1987.253.4.E376. [DOI] [PubMed] [Google Scholar]