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Glucose uptake by the brain on chronic high-protein weight-loss diets with either moderate or low amounts of carbohydrate

  • Gerald E. Lobley (a1), Alexandra M. Johnstone (a1), Claire Fyfe (a1), Graham W. Horgan (a2), Grietje Holtrop (a2), David M. Bremner (a1), Iain Broom (a3), Lutz Schweiger (a4) and Andy Welch (a4)...

Abstract

Previous work has shown that hunger and food intake are lower in individuals on high-protein (HP) diets when combined with low carbohydrate (LC) intakes rather than with moderate carbohydrate (MC) intakes and where a more ketogenic state occurs. The aim of the present study was to investigate whether the difference between HPLC and HPMC diets was associated with changes in glucose and ketone body metabolism, particularly within key areas of the brain involved in appetite control. A total of twelve men, mean BMI 34·9 kg/m2, took part in a randomised cross-over trial, with two 4-week periods when isoenergetic fixed-intake diets (8·3 MJ/d) were given, with 30 % of the energy being given as protein and either (1) a very LC (22 g/d; HPLC) or (2) a MC (182 g/d; HPMC) intake. An 18fluoro-deoxyglucose positron emission tomography scan of the brain was conducted at the end of each dietary intervention period, following an overnight fast (n 4) or 4 h after consumption of a test meal (n 8). On the next day, whole-body ketone and glucose metabolism was quantified using [1,2,3,4-13C]acetoacetate, [2,4-13C]3-hydroxybutyrate and [6,6-2H2]glucose. The composite hunger score was 14 % lower (P= 0·013) for the HPLC dietary intervention than for the HPMC diet. Whole-body ketone flux was approximately 4-fold greater for the HPLC dietary intervention than for the HPMC diet (P< 0·001). The 9-fold difference in carbohydrate intakes between the HPLC and HPMC dietary interventions led to a 5 % lower supply of glucose to the brain. Despite this, the uptake of glucose by the fifty-four regions of the brain analysed remained similar for the two dietary interventions. In conclusion, differences in the composite hunger score observed for the two dietary interventions are not associated with the use of alternative fuels by the brain.

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Corresponding author

*Corresponding author: G. E. Lobley, fax +44 1224 716698, email g.lobley@abdn.ac.uk

References

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1WHO (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 894, 1253, (i–xii).
2Haslam, DW & James, WP (2005) Obesity. Lancet 366, 11971209.
3Atkins, RC (2002) Dr. Atkins' New Diet Revolution. New York, NY: Harper Collins Publishers.
4Weigle, DS, Breen, PA, Matthys, CC, et al. (2005) A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr 82, 4148.
5Foster, GD, Wyatt, HR, Hill, JO, et al. (2003) A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 348, 20822090.
6Soenen, S, Bonomi, AG, Lemmens, SG, et al. (2012) Relatively high-protein or ‘low-carb’ energy-restricted diets for body weight loss and body weight maintenance? Physiol Behav 107, 374380.
7Johnstone, AM, Horgan, GW, Murison, SD, et al. (2008) Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. Am J Clin Nutr 87, 4455.
8Anderson, JW, Konz, EC & Jenkins, DJ (2000) Health advantages and disadvantages of weight-reducing diets: a computer analysis and critical review. J Am Coll Nutr 19, 578590.
9Feinman, RD, Vernon, MC & Westman, EC (2006) Low carbohydrate diets in family practice: what can we learn from an internet-based support group. Nutr J 5, 26.
10Ahima, RS & Antwi, DA (2008) Brain regulation of appetite and satiety. Endocrinol Metab Clin North Am 37, 811823.
11Reinmuth, OM, Scheinberg, P & Bourne B, (1965) Total cerebral blood flow and metabolism. Arch Neurol 12, 4966.
12Hasselbalch, SG, Knudsen, GM, Jakobsen, J, et al. (1994) Brain metabolism during short-term starvation in humans. J Cereb Blood Flow Metab 14, 125131.
13Hawkins, RA, Mans, AM & Davis, DW (1986) Regional ketone body utilization by rat brain in starvation and diabetes. Am J Physiol 250, E169E178.
14Morton, GJ, Cummings, DE, Baskin, DG, et al. (2006) Central nervous system control of food intake and body weight. Nature 443, 289295.
15Blomqvist, G, Thorell, JO, Ingvar, M, et al. (1995) Use of R-beta-[1-11C]hydroxybutyrate in PET studies of regional cerebral uptake of ketone bodies in humans. Am J Physiol 269, E948E959.
16Pan, JW, Rothman, TL, Behar, KL, et al. (2000) Human brain beta-hydroxybutyrate and lactate increase in fasting-induced ketosis. J Cereb Blood Flow Metab 20, 15021507.
17Johnstone, AM, Lobley, GE, Horgan, GW, et al. (2011) Effects of a high-protein, low-carbohydrate v. high-protein, moderate-carbohydrate weight-loss diet on antioxidant status, endothelial markers and plasma indices of the cardiometabolic profile. Br J Nutr 106, 282291.
18Balasse, EO (1979) Kinetics of ketone body metabolism in fasting humans. Metabolism 28, 4150.
19Huang, S-C & Phelps, ME (1986) Principles of tracer kinetic modeling in positron emission tomography and autoradiography. In Positron Emission Tomography and Autoradiography: Principles and Applications for the Brain and Heart, pp. 287346 [Phelps, ME, Mazziotta, JC and Schelbert, HR, editors]. New York, NY: Raven Press.
20Wu, HM, Bergsneider, M, Glenn, TC, et al. (2003) Measurement of the global lumped constant for 2-deoxy-2-[18F]fluoro-d-glucose in normal human brain using [15O]water and 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography imaging. A method with validation based on multiple methodologies. Mol Imaging Biol 5, 3241.
21Avogaro, A, Valerio, A, Gnudi, L, et al. (1992) The effects of different plasma insulin concentrations on lipolytic and ketogenic responses to epinephrine in normal and type 1 (insulin-dependent) diabetic humans. Diabetologia 35, 129138.
22Nosadini, R, Datta, H, Hodson, A, et al. (1980) A possible mechanism for the anti-ketogenic action of alanine in the rat. Biochem J 190, 323332.
23Cobelli, C, Toffolo, G, Avogaro, A, et al. (1990) On the measurement of ketone body turnover. Am J Physiol 259, E890.
24Li, PK, Lee, JT, MacGillivray, MH, et al. (1980) Direct, fixed-time kinetic assays for beta-hydroxybutyrate and acetoacetate with a centrifugal analyzer or a computer-backed spectrophotometer. Clin Chem 26, 17131717.
25Des, RC, Montgomery, JA, Desrochers, S, et al. (1988) Interference of 3-hydroxyisobutyrate with measurements of ketone body concentration and isotopic enrichment by gas chromatography–mass spectrometry. Anal Biochem 173, 96105.
26Calder, AG, Garden, KE, Anderson, SE, et al. (1999) Quantitation of blood and plasma amino acids using isotope dilution electron impact gas chromatography/mass spectrometry with U-(13)C amino acids as internal standards. Rapid Commum Mass Spectrom 13, 20802083.
27Wilson, FA, van den Borne, JJ, Calder, AG, et al. (2009) Tissue methionine cycle activity and homocysteine metabolism in female rats: impact of dietary methionine and folate plus choline. Am J Physiol Endocrinol Metab 296, E702E713.
28Patterson, BW, Carraro, F & Wolfe, RR (1993) Measurement of 15N enrichment in multiple amino acids and urea in a single analysis by gas chromatography/mass spectrometry. Biol Mass Spectrom 22, 518523.
29Cobelli, C, Nosadini, R, Toffolo, G, et al. (1982) Model of the kinetics of ketone bodies in humans. Am J Physiol 243, R7R17.
30Bougneres, PF & Ferre, P (1987) Study of ketone body kinetics in children by a combined perfusion of 13C and 2H3 tracers. Am J Physiol 253, E496E502.
31Ader, M, Ni, TC & Bergman, RN (1997) Glucose effectiveness assessed under dynamic and steady state conditions. Comparability of uptake versus production components. J Clin Invest 99, 11871199.
32Cherrington, AD, Edgerton, D & Sindelar, DK (1998) The direct and indirect effects of insulin on hepatic glucose production in vivo. Diabetologia 41, 987996.
33Chaput, JP, Gilbert, JA, Gregersen, NT, et al. (2010) Comparison of 150-mm versus 100-mm visual analogue scales in free living adult subjects. Appetite 54, 583586.
34Landau, BR, Wahren, J, Chandramouli, V, et al. (1996) Contributions of gluconeogenesis to glucose production in the fasted state. J Clin Invest 98, 378385.
35Meyer, C, Stumvoll, M, Welle, S, et al. (2003) Relative importance of liver, kidney, and substrates in epinephrine-induced increased gluconeogenesis in humans. Am J Physiol Endocrinol Metab 285, E819E826.
36Gerich, JE, Meyer, C, Woerle, HJ, et al. (2001) Renal gluconeogenesis: its importance in human glucose homeostasis. Diabetes Care 24, 382391.
37Wolff, JE & Bergman, EN (1972) Gluconeogenesis from plasma amino acids in fed sheep. Am J Physiol 223, 455460.
38Owen, OE, Morgan, AP, Kemp, HG, et al. (1967) Brain metabolism during fasting. J Clin Invest 46, 15891595.
39Yudkoff, M, Daikhin, Y, Nissim, I, et al. (2004) Ketogenic diet, brain glutamate metabolism and seizure control. Prostaglandins Leukot Essent Fatty Acids 70, 277285.
40Volek, JS, Sharman, MJ, Gomez, AL, et al. (2003) An isoenergetic very low carbohydrate diet improves serum HDL cholesterol and triacylglycerol concentrations, the total cholesterol to HDL cholesterol ratio and postprandial pipemic responses compared with a low fat diet in normal weight, normolipidemic women. J Nutr 133, 27562761.
41Batterham, RL, Heffron, H, Kapoor, S, et al. (2006) Critical role for peptide YY in protein-mediated satiation and body-weight regulation. Cell Metab 4, 223233.
42Veldhorst, M, Smeets, A, Soenen, S, et al. (2008) Protein-induced satiety: effects and mechanisms of different proteins. Physiol Behav 94, 300307.
43Potier, M, Darcel, N & Tome, D (2009) Protein, amino acids and the control of food intake. Curr Opin Clin Nutr Metab Care 12, 5458.
44Lopez, M, Tovar, S, Vazquez, MJ, et al. (2007) Peripheral tissue–brain interactions in the regulation of food intake. Proc Nutr Soc 66, 131155.
45Solomon, A, De Fanti, BA & Martinez, JA (2007) Peripheral ghrelin interacts with orexin neurons in glucostatic signalling. Regul Pept 144, 1724.
46LaManna, JC, Salem, N, Puchowicz, M, et al. (2009) Ketones suppress brain glucose consumption. Adv Exp Med Biol 645, 301306.
47Blomqvist, G, Alvarsson, M, Grill, V, et al. (2002) Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients. Am J Physiol Endocrinol Metab 283, E20E28.
48Bentourkia, M, Tremblay, S, Pifferi, F, et al. (2009) PET study of 11C-acetoacetate kinetics in rat brain during dietary treatments affecting ketosis. Am J Physiol Endocrinol Metab 296, E796E801.
49Hasselbalch, SG, Madsen, PL, Hageman, LP, et al. (1996) Changes in cerebral blood flow and carbohydrate metabolism during acute hyperketonemia. Am J Physiol 270, E746E751.
50Veldhorst, MA, Westerterp, KR, van Vught, AJ, et al. (2010) Presence or absence of carbohydrates and the proportion of fat in a high-protein diet affect appetite suppression but not energy expenditure in normal-weight human subjects fed in energy balance. Br J Nutr 104, 13951405.
51Johnston, CS, Tjonn, SL, Swan, PD, et al. (2006) Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets. Am J Clin Nutr 83, 10551061.
52De Silva, A, Salem, V, Matthews, PM, et al. (2012) The use of functional MRI to study appetite control in the CNS. Exp Diabetes Res 2012, 764017.
53Lizarbe, B, Benitez, A, Sanchez-Montanes, M, et al. (2012) Imaging hypothalamic activity using diffusion weighted magnetic resonance imaging in the mouse and human brain. Neuroimage 64, 448457.
54Rosenbaum, M, Sy, M, Pavlovich, K, et al. (2008) Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli. J Clin Invest 118, 25832591.
55Marty, N, Dallaporta, M & Thorens, B (2007) Brain glucose sensing, counterregulation, and energy homeostasis. Physiology (Bethesda) 22, 241251.
56Levin, BE, Routh, VH, Kang, L, et al. (2004) Neuronal glucosensing: what do we know after 50 years? Diabetes 53, 25212528.
57Page, KA, Seo, D, Belfort-DeAguiar, R, et al. (2011) Circulating glucose levels modulate neural control of desire for high-calorie foods in humans. J Clin Invest 121, 41614169.
58Volkow, ND, Wang, GJ, Telang, F, et al. (2009) Inverse association between BMI and prefrontal metabolic activity in healthy adults. Obesity (Silver Spring) 17, 6065.
59Le, DS, Pannacciulli, N, Chen, K, et al. (2006) Less activation of the left dorsolateral prefrontal cortex in response to a meal: a feature of obesity. Am J Clin Nutr 84, 725731.
60Gautier, JF, Chen, K, Salbe, AD, et al. (2000) Differential brain responses to satiation in obese and lean men. Diabetes 49, 838846.
61Tataranni, PA, Gautier, JF, Chen, K, et al. (1999) Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography. Proc Natl Acad Sci U S A 96, 45694574.

Keywords

Glucose uptake by the brain on chronic high-protein weight-loss diets with either moderate or low amounts of carbohydrate

  • Gerald E. Lobley (a1), Alexandra M. Johnstone (a1), Claire Fyfe (a1), Graham W. Horgan (a2), Grietje Holtrop (a2), David M. Bremner (a1), Iain Broom (a3), Lutz Schweiger (a4) and Andy Welch (a4)...

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