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Citations to this article

Short-term alterations in carbohydrate energy intake in humans. Striking effects on hepatic glucose production, de novo lipogenesis, lipolysis, and whole-body fuel selection.
J M Schwarz, … , D Dare, M K Hellerstein
J M Schwarz, … , D Dare, M K Hellerstein
Published December 1, 1995
Citation Information: J Clin Invest. 1995;96(6):2735-2743. https://doi.org/10.1172/JCI118342.
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Short-term alterations in carbohydrate energy intake in humans. Striking effects on hepatic glucose production, de novo lipogenesis, lipolysis, and whole-body fuel selection.

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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.

Authors

J M Schwarz, R A Neese, S Turner, D Dare, M K Hellerstein

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Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women
CL Cox, KL Stanhope, JM Schwarz, JL Graham, B Hatcher, SC Griffen, AA Bremer, L Berglund, JP McGahan, PJ Havel, NL Keim
European Journal of Clinical Nutrition 2011
Insulin signaling to hepatic lipid metabolism in health and disease
KF Leavens, MJ Birnbaum
Critical Reviews in Biochemistry and Molecular Biology 2011
Impact of High Fat and High Carbohydrate Diets on Liver Metabolism Studied in A Rat Model By A Systems Biology Approach
HC Bertram, LB Larsen, X Chen, PB Jeppesen
Journal of Agricultural and Food Chemistry 2011
Hepatic and peripheral insulin sensitivity and diabetes remission at 1 month after Roux-en-Y gastric bypass surgery in patients randomized to omentectomy
JP Dunn, NN Abumrad, I Breitman, PA Marks-Shulman, CR Flynn, K Jabbour, ID Feurer, RA Tamboli
Diabetes care 2011
Dysregulation of sterol regulatory element binding protein–1c in livers of morbidly obese women is associated with altered suppressor of cytokine signaling–3 and signal transducer and activator of transcription–1 signaling
MB Elam, C Yellaturu, GE Howell, X Deng, GS Cowan, P Kumar, EA Park, ML Hiler, HG Wilcox, TA Hughes, GA Cook, R Raghow
Metabolism 2010
The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome
JS Lim, M Mietus-Snyder, A Valente, JM Schwarz, RH Lustig
Nature Reviews Gastroenterology & Hepatology 2010
Fructose: Metabolic, Hedonic, and Societal Parallels with Ethanol
RH Lustig
Journal of the American Dietetic Association 2010
The protease inhibitor combination lopinavir/ritonavir does not decrease insulin secretion in healthy, HIV-seronegative volunteers
VY Pao, GA Lee, S Taylor, FT Aweeka, JM Schwarz, K Mulligan, M Schambelan, C Grunfeld
AIDS 2010
Carbohydrate for weight and metabolic control: Where do we stand?
KJ Acheson
Nutrition 2010
Nonalcoholic Fatty Liver Disease
JS Ko
The Korean Journal of Gastroenterology 2010
Intake of n-3 polyunsaturated fatty acids and non-alcoholic fatty liver disease: a cross-sectional study in Japanese men and women
J Oya, T Nakagami, S Sasaki, S Jimba, K Murakami, T Kasahara, T Wasada, H Sekiguchi, M Hasegawa, Y Endo, Y Iwamoto
European Journal of Clinical Nutrition 2010
Relationship between body fat mass and free fatty acid kinetics in men and women
B Mittendorfer, F Magkos, E Fabbrini, BS Mohammed, S Klein
Obesity (Silver Spring, Md.) 2009
High fat feeding induces hepatic fatty acid elongation in mice
MH Oosterveer, TH van Dijk, UJ Tietge, T Boer, R Havinga, F Stellaard, AK Groen, F Kuipers, DJ Reijngoud
PloS one 2009
A stable isotope method for the simultaneous measurement of matrix synthesis and cell proliferation in articular cartilage in vivo
KW Li, SA Siraj, EW Cheng, M Awada, MK Hellerstein, SM Turner
Osteoarthritis and Cartilage 2009
Caloric intake and liver dysfunction in critically ill patients
T Grau, A Bonet
Current Opinion in Clinical Nutrition and Metabolic Care 2009
Alterations in hepatic glucose and energy metabolism as a result of calorie and carbohydrate restriction
JD Browning, B Weis, J Davis, S Satapati, M Merritt, CR Malloy, SC Burgess
Hepatology 2008
Glyceroneogenesis is the dominant pathway for triglyceride glycerol synthesis in vivo in the rat
CK Nye, RW Hanson, SC Kalhan
The Journal of biological chemistry 2008
Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause
R Taylor
Diabetologia 2008
Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome
JS Volek, ML Fernandez, RD Feinman, SD Phinney
Progress in Lipid Research 2008
Dietary sugars stimulate fatty acid synthesis in adults
EJ Parks, LE Skokan, MT Timlin, CS Dingfelder
The Journal of nutrition 2008
Changes induced by dietary energy intake and divergent selection for muscle fat content in rainbow trout (Oncorhynchus mykiss), assessed by transcriptome and proteome analysis of the liver
CI Kolditz, G Paboeuf, M Borthaire, D Esquerré, M SanCristobal, F Lefèvre, F Médale
BMC Genomics 2008
Short-term High Dietary Fructose Intake had No Effects on Insulin Sensitivity and Secretion or Glucose and Lipid Metabolism in Healthy, Obese Adolescents
AL Sunehag, G Toffolo, M Campioni, DM Bier, MW Haymond
Journal of Pediatric Endocrinology and Metabolism 2008
Effets métaboliques différentiels des sucres
J Girard
Cahiers de Nutrition et de Diététique 2008
Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 d of high-carbohydrate feeding
MF Chong, L Hodson, AS Bickerton, R Roberts, M Neville, F Karpe, KN Frayn, BA Fielding
The American journal of clinical nutrition 2008
Glyceroneogenesis Is the Dominant Pathway for Triglyceride Glycerol Synthesis in Vivo in the Rat
CK Nye, RW Hanson, SC Kalhan
The Journal of biological chemistry 2008
Obesity
CY Chen, J Blumberg
Obesity 2007
Metabolic interaction of dietary sugars and plasma lipids with a focus on mechanisms and de novo lipogenesis
MF Chong, BA Fielding, KN Frayn
Proceedings of the Nutrition Society 2007
Novel food ingredients for weight control
G Gerstner, M Vrese
Novel food ingredients for weight control 2007
Traité de nutrition artificielle de l’adulte
N Cano, D Barnoud, SM Schneider, MP Vasson, M Hasselmann, X Leverve
2007
Use of stable isotopes to evaluate the functional effects of nutrients
M Beylot
Current Opinion in Clinical Nutrition and Metabolic Care 2006
Effect of short-term starvation versus high-fat diet on intramyocellular triglyceride accumulation and insulin resistance in physically fit men: Intramyocellular triglyceride, insulin resistance and carbohydrate restriction
NA Johnson, SR Stannard, DS Rowlands, PG Chapman, CH Thompson, H O'Connor, T Sachinwalla, MW Thompson
Experimental Physiology 2006
Stable isotope methods for the in vivo measurement of lipogenesis and triglyceride metabolism1,2
EJ Murphy
Journal of animal science 2006
Lipid metabolism in human skeletal muscle cells: effects of palmitate and chronic hyperglycaemia
V Aas, M Rokling-Andersen, AJ Wensaas, GH Thoresen, ET Kase, AC Rustan
Acta Physiologica Scandinavica 2005
Nutrition-/diet-induced changes in gene expression in white adipose tissue
H Al-Hasani, HG Joost
Best Practice & Research Clinical Endocrinology & Metabolism 2005
Effects of weight loss and calorie restriction on carbohydrate metabolism
M Manco, G Mingrone
Current Opinion in Clinical Nutrition and Metabolic Care 2005
Two days of a very low calorie diet reduces endogenous glucose production in obese type 2 diabetic patients despite the withdrawal of blood glucose–lowering therapies including insulin
IM Jazet, H Pijl, M Frölich, JA Romijn, AE Meinders
Metabolism 2005
Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men
David Faeh, Kaori Minehira, Jean-Marc Schwarz, Raj Periasamy, Raj Periasami, Seongsu Park, Park Seongsu, Luc Tappy
Diabetes 2005
Energy deficit without reducing dietary carbohydrate alters resting carbohydrate oxidation and fatty acid availability
JF Horowitz, AE Kaufman, AK Fox, MP Harber
Journal of applied physiology 2005
Hepatic de Novo Lipogenesis in Stable Low-Birth-Weight Infants During Exclusive Breast Milk Feedings and During Parenteral Nutrition
M Garg, S Bassilian, C Bell, S Lee, WN Lee
JPEN. Journal of parenteral and enteral nutrition 2005
Temporal pattern of de novo lipogenesis in the postprandial state in healthy men
MT Timlin, EJ Parks
The American journal of clinical nutrition 2005
New stable isotope–mass spectrometric techniques for measuring fluxes through intact metabolic pathways in mammalian systems: introduction of moving pictures into functional genomics and biochemical phenotyping
MK Hellerstein
Metabolic Engineering 2004
Basal and postprandial substrate oxidation rates in obese women receiving two test meals with different protein content
I Labayen, N Dı́ez, D Parra, A González, JA Martı́nez
Clinical Nutrition 2004
Cholesterol Synthesis and De Novo Lipogenesis in Premature Infants Determined by Mass Isotopomer Distribution Analysis
LN Renfurm, RH Bandsma, HJ Verkade, CV Hulzebos, T Dijk, T Boer, F Stellaard, F Kuipers, PJ Sauer
Pediatric Research 2004
Indinavir increases glucose production in healthy HIV-negative men:
JM Schwarz, GA Lee, S Park, MA Noor, J Lee, M Wen, JC Lo, K Mulligan, M Schambelan, C Grunfeld
AIDS 2004
The metabolic effects of lopinavir/ritonavir in HIV-negative men:
GA Lee, T Seneviratne, MA Noor, JC Lo, JM Schwarz, FT Aweeka, K Mulligan, M Schambelan, C Grunfeld
AIDS 2004
Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2 H 2 O
A Strawford, F Antelo, M Christiansen, MK Hellerstein
American journal of physiology. Endocrinology and metabolism 2004
The Human Fatty Acid Synthase Gene and De Novo Lipogenesis Are Coordinately Regulated in Human Adipose Tissue
Y Wang, BJ Voy, S Urs, S Kim, M Soltani-Bejnood, N Quigley, YR Heo, M Standridge, B Andersen, M Dhar, R Joshi, P Wortman, JW Taylor, J Chun, M Leuze, K Claycombe, AM Saxton, N Moustaid-Moussa
The Journal of nutrition 2004
Nutrition and Heart Disease
A R.P.Walker
Nutrition and Heart Disease 2003
INVIVOMEASUREMENT OFFLUXES THROUGHMETABOLICPATHWAYS: The Missing Link in Functional Genomics and Pharmaceutical Research
MK Hellerstein
Annual Review of Nutrition 2003
Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets
K Promrat, G Lutchman, GI Uwaifo, RJ Freedman, A Soza, T Heller, E Doo, M Ghany, A Premkumar, Y Park, TJ Liang, JA Yanovski, DE Kleiner, JH Hoofnagle
The American journal of clinical nutrition 2003
Glucose oversupply increases Δ9-desaturase expression and its metabolites in rat skeletal muscle
B Houdali, HG Wahl, M Kresi, V Nguyen, M Haap, F Machicao, HP Ammon, W Renn, ED Schleicher, HU Häring
Diabetologia 2003
Measurement of TG synthesis and turnover in vivo by 2 H 2 O incorporation into the glycerol moiety and application of MIDA
SM Turner, EJ Murphy, RA Neese, F Antelo, T Thomas, A Agarwal, C Go, MK Hellerstein
American journal of physiology. Endocrinology and metabolism 2003
Alterations in lipid kinetics in men with HIV-dyslipidemia
DN Reeds, B Mittendorfer, BW Patterson, WG Powderly, KE Yarasheski, S Klein
American journal of physiology. Endocrinology and metabolism 2003
Increased lipogenesis and resistance of lipoproteins to oxidative modification in two patients with glycogen storage disease type 1a
RH Bandsma, JP Rake, G Visser, RA Neese, MK Hellerstein, W Duyvenvoorde, HM Princen, F Stellaard, GP Smit, F Kuipers
The Journal of Pediatrics 2002
Protein and diabetes: Much advice, little research
MJ Franz
Current Diabetes Reports 2002
Skeletal Muscle Triglycerides
DE Kelley
Annals of the New York Academy of Sciences 2002
MUSCLETRIGLYCERIDE ANDINSULINRESISTANCE
DE Kelley, BH Goodpaster, L Storlien
Annual Review of Nutrition 2002
Changes in fat synthesis influenced by dietary macronutrient content
EJ Parks
Proceedings of the Nutrition Society 2002
Insulin Stimulation of Hepatic Triacylglycerol Secretion in the Insulin-Replete State
VA Zammit
Annals of the New York Academy of Sciences 2002
Measuring synthesis rates of muscle creatine kinase and myosin with stable isotopes and mass spectrometry
C Papageorgopoulos, K Caldwell, H Schweingrubber, RA Neese, CH Shackleton, M Hellerstein
Analytical Biochemistry 2002
M USCLE T RIGLYCERIDE AND I NSULIN R ESISTANCE
DE Kelley, BH Goodpaster, L Storlien
Annual Review of Nutrition 2002
Disordered Fat Storage and Mobilization in the Pathogenesis of Insulin Resistance and Type 2 Diabetes
GF Lewis, A Carpentier, K Adeli, A Giacca
Endocrine reviews 2002
Differential Effects of Fenofibrate or Simvastatin Treatment of Rats on Hepatic Microsomal Overt and Latent Diacylglycerol Acyltransferase Activities
IJ Waterman, VA Zammit
Diabetes 2002
Hydroxycitrate Has Long-Term Effects on Feeding Behavior, Body Weight Regain and Metabolism after Body Weight Loss in Male Rats
M Leonhardt, W Langhans
The Journal of nutrition 2002
New data and new concepts on the role of the liver in glucose homeostasis
L Tappy, K Minehira
Current Opinion in Clinical Nutrition and Metabolic Care 2001
Metabolic effects of indinavir in healthy HIV-seronegative men
MA Noor, JC Lo, K Mulligan, JM Schwarz, RA Halvorsen, M Schambelan, C Grunfeld
AIDS 2001
Effect of nicotinic acid administration on hepatic very low density lipoprotein-triglyceride production
W Wang, A Basinger, RA Neese, B Shane, SA Myong, M Christiansen, MK Hellerstein
American journal of physiology. Endocrinology and metabolism 2001
Hepatic de novo Lipogenesis after Liver Transplantation
K Minehira, V Novel-Chaté, JM Schwarz, M Gillet, R Darioli, R Chioléro, L Tappy
JPEN. Journal of parenteral and enteral nutrition 2001
Dietary fat content alters insulin-mediated glucose metabolism in healthy men
PH Bisschop, J de Metz, MT Ackermans, E Endert, H Pijl, F Kuipers, AJ Meijer, HP Sauerwein, JA Romijn
The American journal of clinical nutrition 2001
Postprandial de novo lipogenesis and metabolic changes induced by a high-carbohydrate, low-fat meal in lean and overweight men
I Marques-Lopes, D Ansorena, I Astiasaran, L Forga, JA Martínez
The American journal of clinical nutrition 2001
No common energy currency: de novo lipogenesis as the road less traveled
MK Hellerstein
The American journal of clinical nutrition 2001
De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women
RM McDevitt, SJ Bott, M Harding, WA Coward, LJ Bluck, AM Prentice
The American journal of clinical nutrition 2001
Is Fat Intake a Risk Factor for Fat Gain in Children?
E Jéquier
The Journal of clinical endocrinology and metabolism 2001
Metabolic effects of indinavir in healthy HIV-seronegative men.
Noor MA, Lo JC, Mulligan K, Schwarz JM, Halvorsen RA, Schambelan M, Grunfeld C
AIDS 2001
Is In Vivo Nuclear Magnetic Resonance Spectroscopy Currently a Quantitative Method for Whole-body Carbohydrate Metabolism?
E Murphy, M Hellerstein
Nutrition Reviews 2000
Effects of isoenergetic overfeeding of either carbohydrate or fat in young men
O Lammert, N Grunnet, P Faber, KS Bjørnsbo, J Dich, LO Larsen, RA Neese, MK Hellerstein, B Quistorff
British Journal of Nutrition 2000
Effects of nicotinic acid on fatty acid kinetics, fuel selection, and pathways of glucose production in women
W Wang, A Basinger, RA Neese, M Christiansen, MK Hellerstein
American journal of physiology. Endocrinology and metabolism 2000
Carbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms
EJ Parks, MK Hellerstein
The American journal of clinical nutrition 2000
Fat and carbohydrate balances during adaptation to a high-fat diet
SR Smith, L de Jonge, JJ Zachwieja, H Roy, T Nguyen, JC Rood, MM Windhauser, GA Bray
The American journal of clinical nutrition 2000
Effects of acute (−)-hydroxycitrate supplementation on substrate metabolism at rest and during exercise in humans
LJ van Loon, JJ van Rooijen, B Niesen, H Verhagen, WH Saris, AJ Wagenmakers
The American journal of clinical nutrition 2000
From Nutrition Support to Pharmacologic Nutrition in the ICU
C Pichard, KA Kudsk
2000
Obesity: from molecules to man
SA Jebb
Proceedings of the Nutrition Society 1999
Metabolic adaptations to dietary fat malabsorption in chylomicron-deficient mice
HR Jung, SM Turner, RA Neese, SG Young, MK Hellerstein
Biochemical Journal 1999
De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption
SQ Siler, RA Neese, MK Hellerstein
The American journal of clinical nutrition 1999
Regulation of Body Weight in Humans
E Jéquier, L Tappy
Physiological reviews 1999
Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss
DE Kelley, B Goodpaster, RR Wing, JA Simoneau
American journal of physiology. Endocrinology and metabolism 1999
Modulation of triglyceride metabolism by glucocorticoids in diet-induced obesity
L Mantha, E Palacios, Y Deshaies
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 1999
Decreased Production Rates of VLDL Triglycerides and ApoB-100 in Subjects Heterozygous for Familial Hypobetalipoproteinemia
N Elias, BW Patterson, G Schonfeld
Arteriosclerosis, thrombosis, and vascular biology 1999
Co-ordination of hepatic and adipose tissue lipid metabolism after oral glucose
J Bülow, L Simonsen, D Wiggins, SM Humphreys, KN Frayn, D Powell, GF Gibbons
Journal of lipid research 1999
Use of deuterium oxide to measure de novo fatty acid synthesis in normal subjects consuming different dietary fatty acid composition1
S Konrad, S Cook, Y Goh, M French, M Clandinin
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1998
Role of muscle in triglyceride metabolism
BH Goodpaster, DE Kelley
Current Opinion in Lipidology 1998
Nutritional hepatic steatosis and mortality after burn injury in rats
B Mittendorfer, MG Jeschke, SE Wolf, LS Sidossis
Clinical Nutrition 1998
Effects of isoenergetic glucose-based or lipid-based parenteral nutrition on glucose metabolism, de novo lipogenesis, and respiratory gas exchanges in critically ill patients:
L Tappy, JM Schwarz, P Schneiter, C Cayeux, JP Revelly, CK Fagerquist, E Jequier, R Chiolero
Critical Care Medicine 1998
VLDL-triglyceride production after alcohol ingestion, studied using [2-13C1] glycerol
SQ Siler, RA Neese, EJ Parks, MK Hellerstein
Journal of lipid research 1998
Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study
MK Hellerstein, RA Neese, P Linfoot, M Christiansen, S Turner, A Letscher
Journal of Clinical Investigation 1997
Regulation of fatty acid synthase (FAS)
CF Semenkovich
Progress in Lipid Research 1997
Lipoprotein lipase controls fatty acid entry into adipose tissue, but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase
PH Weinstock, S Levak-Frank, LC Hudgins, H Radner, JM Friedman, R Zechner, JL Breslow
Proceedings of the National Academy of Sciences 1997
Glucose production and gluconeogenesis in adults with uncomplicated falciparum malaria
E Dekker, JA Romijn, K Ekberg, J Wahren, HV Thien, MT Ackermans, LT Thuy, V Chandramouli, PA Kager, BR Landau, HP Sauerwein
American journal of physiology. Endocrinology and metabolism 1997
Clinical Research in Diabetes and Obesity
B Draznin, R Rizza
1997
Chronic exogenous insulin and chronic carbohydrate supplementation increase de novo VLDL triglyceride fatty acid production in rats
J Park, S Lemieux, GF Lewis, A Kuksis, G Steiner
Journal of lipid research 1997
Synthesis of fat in response to alterations in diet: Insights from new stable isotope methodologies
MK Hellerstein
Lipids 1996

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