title: Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat.
abstract: BACKGROUND
  Consumption of high-fructose diets promotes hepatic fatty acid synthesis (de novo lipogenesis [DNL]) and an atherogenic lipid profile. It is unclear whether these effects occur independent of positive energy balance and weight gain.
  
  
  OBJECTIVE
  We compared the effects of a high-fructose, (25% of energy content) weight-maintaining diet to those of an isocaloric diet with the same macronutrient distribution but in which complex carbohydrate (CCHO) was substituted for fructose.
  
  
  METHODS
  Eight healthy men were studied as inpatients for consecutive 9-day periods. Stable isotope tracers were used to measure fractional hepatic DNL and endogenous glucose production (EGP) and its suppression during a euglycemic-hyperinsulinemic clamp. Liver fat was measured by magnetic resonance spectroscopy.
  
  
  RESULTS
  Weight remained stable. Regardless of the order in which the diets were fed, the high-fructose diet was associated with both higher DNL (average, 18.6 ± 1.4% vs 11.0 ± 1.4% for CCHO; P = .001) and higher liver fat (median, +137% of CCHO; P = .016) in all participants. Fasting EGP and insulin-mediated glucose disposal did not differ significantly, but EGP during hyperinsulinemia was greater (0.60 ± 0.07 vs 0.46 ± 0.06 mg/kg/min; P = .013) with the high-fructose diet, suggesting blunted suppression of EGP.
  
  
  CONCLUSIONS
  Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets.
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Schwarz
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Noworolski
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wen
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Artem
authors.initials: A
authors.lastname: Dyachenko
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Prior
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Weinberg
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Herraiz
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Viva W
authors.initials: VW
authors.lastname: Tai
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bergeron
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Bersot
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Madhu N
authors.initials: MN
authors.lastname: Rao
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Morris
authors.initials: M
authors.lastname: Schambelan
authors.affiliation: Touro University (J.M.S., A.D., J.L.P., N.B.), Vallejo, California 94594; Department of Medicine (J.M.S., M.E.W., T.P.B., M.N.R., M.S., K.M.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology (J.M.S., M.J.W., M.E.W., V.W.T., M.N.R., M.S., K.M.), San Francisco General Hospital, San Francisco, California 94110; Department of Radiology and Biomedical Imaging (S.M.N.), University of California, San Francisco, San Francisco, California 94143; UCSF Clinical and Translational Science Institute Clinical Research Center (L.A.H., V.W.T.), San Francisco, California 94143; and The Gladstone Institute of Cardiovascular Disease (T.P.B.), San Francisco, California 94158.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D001835:Body Weight / Q000187:drug effects*; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D004040:Dietary Carbohydrates; D005632:Fructose; D005947:Glucose
references.citation: Am J Clin Nutr. 2007 Jun;85(6):1511-20
references.pmid: 17556686
references.citation: Am J Physiol. 1999 Jun;276(6 Pt 1):E1146-70
references.pmid: 10362629
references.citation: Diabetologia. 2008 Nov;51(11):1947-53
references.pmid: 18762907
references.citation: Magn Reson Imaging. 2009 May;27(4):570-6
references.pmid: 18993007
references.citation: J Clin Invest. 2009 May;119(5):1322-34
references.pmid: 19381015
references.citation: Am J Clin Nutr. 2009 Jun;89(6):1760-5
references.pmid: 19403641
references.citation: J Nutr. 2009 Jun;139(6):1228S-1235S
references.pmid: 19403716
references.citation: Curr Opin Cardiol. 2009 Jul;24(4):345-50
references.pmid: 19424059
references.citation: Circulation. 2009 Sep 15;120(11):1011-20
references.pmid: 19704096
references.citation: Physiol Rev. 2010 Jan;90(1):23-46
references.pmid: 20086073
references.citation: Hepatology. 2010 Feb;51(2):679-89
references.pmid: 20041406
references.citation: Am J Clin Nutr. 2000 Nov;72(5):1128-34
references.pmid: 11063439
references.citation: Diabetes. 2002 Jan;51(1):7-18
references.pmid: 11756317
references.citation: Am J Clin Nutr. 2003 Jan;77(1):43-50
references.pmid: 12499321
references.citation: Nat Rev Gastroenterol Hepatol. 2010 May;7(5):251-64
references.pmid: 20368739
references.citation: Br J Nutr. 2010 Apr;103(7):939-43
references.pmid: 19930762
references.citation: Am J Clin Nutr. 2004 Apr;79(4):537-43
references.pmid: 15051594
references.citation: Diabetes Metab. 2010 Jun;36(3):244-6
references.pmid: 20483648
references.citation: Trends Endocrinol Metab. 2011 Feb;22(2):60-5
references.pmid: 21067942
references.citation: J Clin Endocrinol Metab. 2011 Mar;96(3):861-8
references.pmid: 21252253
references.citation: Br J Nutr. 2011 Jul;106(1):79-86
references.pmid: 21396140
references.citation: Lancet. 2011 Aug 27;378(9793):804-14
references.pmid: 21872749
references.citation: Curr Opin Lipidol. 2011 Dec;22(6):479-88
references.pmid: 22002020
references.citation: Am J Clin Nutr. 2012 Feb;95(2):283-9
references.pmid: 22205311
references.citation: Curr Opin Endocrinol Diabetes Obes. 2012 Apr;19(2):93-6
references.pmid: 22262000
references.citation: N Engl J Med. 2012 Oct 11;367(15):1407-16
references.pmid: 22998339
references.citation: N Engl J Med. 2012 Oct 11;367(15):1397-406
references.pmid: 22998340
references.citation: Diabetes Care. 2013 Jan;36(1):150-6
references.pmid: 22933433
references.citation: JAMA. 2013 Jan 2;309(1):63-70
references.pmid: 23280226
references.citation: BMJ. 2013;346:e7492
references.pmid: 23321486
references.citation: PLoS One. 2013;8(2):e57873
references.pmid: 23460912
references.citation: Diabetologia. 2013 Jul;56(7):1520-30
references.pmid: 23620057
references.citation: Atherosclerosis. 2014 Jan;232(1):125-33
references.pmid: 24401226
references.citation: Ann Intern Med. 2014 Sep 2;161(5):309-18
references.pmid: 25178568
references.citation: J Clin Endocrinol Metab. 2004 Jun;89(6):2963-72
references.pmid: 15181085
references.citation: Am J Physiol. 1979 Sep;237(3):E214-23
references.pmid: 382871
references.citation: Metabolism. 1988 Mar;37(3):287-301
references.pmid: 3278194
references.citation: J Clin Invest. 1995 Dec;96(6):2735-43
references.pmid: 8675642
references.citation: Am J Clin Nutr. 2007 Aug;86(2):285-300
references.pmid: 17684197