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Fructose and the link to the metabolic
syndrome
                            Piero Portincasa, MD, PhD
                                 Leonilde Bonfrate,MD
            Department of Internal and Public Medicine
                     University of Bari Medical School
                                           Bari – Italy
                     p.portincasa@semeiotica.uniba.it
NAFLD: Associated with Metabolic Syndrome




                                                       17/09/12
                                 Metabolic Syndrome

           Obesity




                                                      P. Portincasa, UNIBA
          Diabetes
         Dyslipidemia




EPIDEMIA DEL III MILLENNIO
The “BOTERO Syndrome”




                                        17/09/12
                                       P. Portincasa, UNIBA
                                   3


29.04.05
17/09/12
Food fast!




                               4
             Fast food!    P.
                          Porti
                          ncas
                           a,
                          UNI
5


FRUITS AND VEGETABLES
                    P.
                    Portincasa,
                                  17/09/1
                                  2
                         UNIBA
6

                                                   P.            17/09/1
                                                   Portincasa,   2

FRUITS AND VEGETABLES
                                                   UNIBA



 •
     Consumption is inversely related to the risk of coronary
     heart disease (CHD) and stroke

The effect of fruit and vegetable intake on risk for coronary heart disease. AU
Joshipura KJ; Hu FB; Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G;
Ascherio A; Rosner B; Spiegelman D; Willett WC SO Ann Intern Med 2001 Jun
19;134(12):1106-14.

Legume consumption and risk of coronary heart disease in US men and women:
NHANES I Epidemiologic Follow-up Study. AU Bazzano LA; He J; Ogden LG; Loria C;
Vupputuri S; Myers L; Whelton PK SO Arch Intern Med 2001 Nov 26;161(21):2573-8.
7

                                                            P.               17/09/1
                                                            Portincasa,      2
The effect of fruit and vegetable intake on risk for coronary heart disease. AU Joshipura KJ; Hu FB;
                                                            UNIBA
Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G; Ascherio A; Rosner B; Spiegelman D;
Willett WC SO Ann Intern Med 2001 Jun 19;134(12):1106-14.


 •
     The Nurses' Health Study and the Health Professionals' Follow-Up
     Study
 •
     84 251 women 34 to 59 yrs of age who for 14 yrs and 42 148 men 40 to
     75 yrs followed for 8 yrs
 •
     Incidence of nonfatal myocardial infarction or fatal coronary heart
     disease (1127 cases in women and 1063 cases in men).
 •
     Diet assessed by using food-frequency questionnaires

 •
     CONCLUSIONS: Consumption of fruits and
     vegetables, particularly green leafy vegetables and
     vitamin C-rich fruits and vegetables, appears to have a
8

                                          P.          17/09/1
                                          Portincasa, 2
Fruit and vegetable consumption and     stroke: meta-analysis
                                          UNIBA          of
cohort studies. He FJ; Nowson CA; MacGregor GA Lancet. 2006
Jan 28;367(9507):320-6.  
•
    MEDLINE, EMBASE, the Cochrane Library, and bibliographies
    of retrieved articles
•
    8 studies, 9 independent cohorts
•
    257,551 individuals (4917 stroke events), average follow-up of 13
    years
•
    relative risk of stroke was 0.89 (95% CI 0.83-0.97) for those
    with 3 to 5 servings per day, and 0.74 (0.69-0.79) >5 servings
    per day.
•
    Fruit and vegetables significant protective effect on both
    ischaemic and haemorrhagic stroke.
9

                                                  P.            17/09/1
                                                  Portincasa,   2
                                                  UNIBA




Lyn M Steffen Jan 28, 2006, The Lancet, Vol. 367 No. 9507 pp 278-279
10

                                       P.            17/09/1
                                       Portincasa,   2
                                       UNIBA




    5 a day!

Lancet. 2006 Jan 28;367(9507):320-6.
FRUCTOSE........FRIEND…
     OR ENEMY?
Fructose consumption

         16–20 grams/day (only fresh fruits)




                                               74%




85–100 grams/day         Basciano et al; Nutr Metab (Lond). 2005; 2: 5.
Dietary fructose
                                         monosaccharide

 Fructose
  •   a free hexose
  •   as the disaccharide (sucrose:
      glucose-fructose)
  •   in a polymerized form (fructans)
 Up  to one half of the population
  unable to completely absorb a
                                            sucrose
  load of 25 g
 4 Kcal / g

 Glycemic index: 23 (sucrose:
  57)
According to the USDA database, foods with more fructose than glucose include:



                                        Fructose (grams /       Glucose (grams /
                 Food
                                        100 grams)              100 grams)
                     High fructose
                                               55 to 90               45 to 10
                      corn syrup
                        Sucrose
                                                  50                     50
                    (for reference)
                          Honey                  40.9                   35.7
                          Raisins                29.8                   27.8
                           Pears                 6.2                     2.8
                          Apples                 5.9                     2.4
                         Fruit juice
                        e.g. Apples,            5 to 7                  2 to 3
                           Pears
                     Watermelon                  3.4                     1.6
Metabolic pathways of entry of (A) glucose and
                       (B) fructose into the glycolytic pathway of the
                                             CNS




            Cha S H et al. PNAS 2008;105:16871-16875


©2008 by National Academy of Sciences
Central administration of fructose




 Fructose exerts an orexigenic effect

       Seung Hun Cha et al., Proc Natl Acad Sci U S A. November 2008
 The brain, like the liver, possesses a unique set of
  enzymes that enables fructose to bypass the rate-
  limiting step in glycolysis and thereby rapidly deplete
  ATP in the hypothalamus
 The central administration of fructose rapidly lowers
  ATP, increases P-AMPK and P-ACC (acetyl-CoA
  carboxylase ), and decreases malonyl-CoA in the
  hypothalamus, whereas centrally administered glucose
  has the inverse effects.
FRUCTOSE IN THE LIVER

        A high flux of fructose to the liver (the main organ
          capable of metabolizing this simple carbohydrate)

1.   perturbs glucose metabolism and glucose uptake
     pathways (Fructose-induced insulin resistance)
2.   leads to a significantly enhanced rate of de novo
     lipogenesis and triglyceride (TG) synthesis, driven
     by the high flux of glycerol and acyl portions of TG
     molecules from fructose catabolism.
MTP (microsomial triglyceride
 transfer protein)


Basciano et al. Nutr Metab (Lond). 2005; 2: 5.
Increased fructose intake



                                upregulation of
NAFLD                           KHK
                                (fructokinase)



                              fructose-induced ATP depletion



        Hepatic necroinflammation
keypoints
High dietary
 intake of
 fructose



                            NAFLD



               insulin
dyslipidemia   resistance



                                    metabolic
                                    syndrome

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Fructose and the link to the metabolic syndrome - di Piero Portincasa e Leonilde Bonfrate

  • 1. Fructose and the link to the metabolic syndrome Piero Portincasa, MD, PhD Leonilde Bonfrate,MD Department of Internal and Public Medicine University of Bari Medical School Bari – Italy p.portincasa@semeiotica.uniba.it
  • 2. NAFLD: Associated with Metabolic Syndrome 17/09/12 Metabolic Syndrome Obesity P. Portincasa, UNIBA Diabetes Dyslipidemia EPIDEMIA DEL III MILLENNIO
  • 3. The “BOTERO Syndrome” 17/09/12 P. Portincasa, UNIBA 3 29.04.05
  • 4. 17/09/12 Food fast! 4 Fast food! P. Porti ncas a, UNI
  • 5. 5 FRUITS AND VEGETABLES P. Portincasa, 17/09/1 2 UNIBA
  • 6. 6 P. 17/09/1 Portincasa, 2 FRUITS AND VEGETABLES UNIBA • Consumption is inversely related to the risk of coronary heart disease (CHD) and stroke The effect of fruit and vegetable intake on risk for coronary heart disease. AU Joshipura KJ; Hu FB; Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G; Ascherio A; Rosner B; Spiegelman D; Willett WC SO Ann Intern Med 2001 Jun 19;134(12):1106-14. Legume consumption and risk of coronary heart disease in US men and women: NHANES I Epidemiologic Follow-up Study. AU Bazzano LA; He J; Ogden LG; Loria C; Vupputuri S; Myers L; Whelton PK SO Arch Intern Med 2001 Nov 26;161(21):2573-8.
  • 7. 7 P. 17/09/1 Portincasa, 2 The effect of fruit and vegetable intake on risk for coronary heart disease. AU Joshipura KJ; Hu FB; UNIBA Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G; Ascherio A; Rosner B; Spiegelman D; Willett WC SO Ann Intern Med 2001 Jun 19;134(12):1106-14. • The Nurses' Health Study and the Health Professionals' Follow-Up Study • 84 251 women 34 to 59 yrs of age who for 14 yrs and 42 148 men 40 to 75 yrs followed for 8 yrs • Incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). • Diet assessed by using food-frequency questionnaires • CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a
  • 8. 8 P. 17/09/1 Portincasa, 2 Fruit and vegetable consumption and stroke: meta-analysis UNIBA of cohort studies. He FJ; Nowson CA; MacGregor GA Lancet. 2006 Jan 28;367(9507):320-6.   • MEDLINE, EMBASE, the Cochrane Library, and bibliographies of retrieved articles • 8 studies, 9 independent cohorts • 257,551 individuals (4917 stroke events), average follow-up of 13 years • relative risk of stroke was 0.89 (95% CI 0.83-0.97) for those with 3 to 5 servings per day, and 0.74 (0.69-0.79) >5 servings per day. • Fruit and vegetables significant protective effect on both ischaemic and haemorrhagic stroke.
  • 9. 9 P. 17/09/1 Portincasa, 2 UNIBA Lyn M Steffen Jan 28, 2006, The Lancet, Vol. 367 No. 9507 pp 278-279
  • 10. 10 P. 17/09/1 Portincasa, 2 UNIBA 5 a day! Lancet. 2006 Jan 28;367(9507):320-6.
  • 12. Fructose consumption 16–20 grams/day (only fresh fruits) 74% 85–100 grams/day Basciano et al; Nutr Metab (Lond). 2005; 2: 5.
  • 13. Dietary fructose monosaccharide  Fructose • a free hexose • as the disaccharide (sucrose: glucose-fructose) • in a polymerized form (fructans)  Up to one half of the population unable to completely absorb a sucrose load of 25 g  4 Kcal / g  Glycemic index: 23 (sucrose: 57)
  • 14. According to the USDA database, foods with more fructose than glucose include: Fructose (grams / Glucose (grams / Food 100 grams) 100 grams) High fructose 55 to 90 45 to 10 corn syrup Sucrose 50 50 (for reference) Honey 40.9 35.7 Raisins 29.8 27.8 Pears 6.2 2.8 Apples 5.9 2.4 Fruit juice e.g. Apples, 5 to 7 2 to 3 Pears Watermelon 3.4 1.6
  • 15. Metabolic pathways of entry of (A) glucose and (B) fructose into the glycolytic pathway of the CNS Cha S H et al. PNAS 2008;105:16871-16875 ©2008 by National Academy of Sciences
  • 16. Central administration of fructose Fructose exerts an orexigenic effect Seung Hun Cha et al., Proc Natl Acad Sci U S A. November 2008
  • 17.  The brain, like the liver, possesses a unique set of enzymes that enables fructose to bypass the rate- limiting step in glycolysis and thereby rapidly deplete ATP in the hypothalamus  The central administration of fructose rapidly lowers ATP, increases P-AMPK and P-ACC (acetyl-CoA carboxylase ), and decreases malonyl-CoA in the hypothalamus, whereas centrally administered glucose has the inverse effects.
  • 18. FRUCTOSE IN THE LIVER  A high flux of fructose to the liver (the main organ capable of metabolizing this simple carbohydrate) 1. perturbs glucose metabolism and glucose uptake pathways (Fructose-induced insulin resistance) 2. leads to a significantly enhanced rate of de novo lipogenesis and triglyceride (TG) synthesis, driven by the high flux of glycerol and acyl portions of TG molecules from fructose catabolism.
  • 19. MTP (microsomial triglyceride transfer protein) Basciano et al. Nutr Metab (Lond). 2005; 2: 5.
  • 20. Increased fructose intake upregulation of NAFLD KHK (fructokinase) fructose-induced ATP depletion Hepatic necroinflammation
  • 21. keypoints High dietary intake of fructose NAFLD insulin dyslipidemia resistance metabolic syndrome

Editor's Notes

  1. NAFLD: Associated with Metabolic Syndrome NAFLD is associated with the metabolic syndrome. The metabolic syndrome is a constellation of disorders, including obesity, type 2 diabetes and dyslipidemia, that often cluster together. The prevalence of insulin resistance is very high in individuals with the metabolic syndrome. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917-923. Shirai K. Obesity as the core of the metabolic syndrome and the management of coronary heart disease. Curr Med Res Opin 2004;20:295-304. Miller JL. Insulin resistance syndrome. Description, pathogenesis, and management. Postgrad Med 2003;Spec No:27-34.
  2. Il sonnellino (1982 - olio su tela)
  3. 2 TI The effect of fruit and vegetable intake on risk for coronary heart disease. AU Joshipura KJ; Hu FB; Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G; Ascherio A; Rosner B; Spiegelman D; Willett WC SO Ann Intern Med 2001 Jun 19;134(12):1106-14.     BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease.   AD Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. PMID 11412050 3 TI Legume consumption and risk of coronary heart disease in US men and women: NHANES I Epidemiologic Follow-up Study. AU Bazzano LA; He J; Ogden LG; Loria C; Vupputuri S; Myers L; Whelton PK SO Arch Intern Med 2001 Nov 26;161(21):2573-8.     BACKGROUND: Soybean protein and dietary fiber supplementation reduce serum cholesterol in randomized controlled trials. Consumption of legumes, which are high in bean protein and water-soluble fiber, may be associated with a reduced risk of coronary heart disease (CHD). METHODS: A total of 9632 men and women who participated in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (NHEFS) and were free of cardiovascular disease (CVD) at their baseline examination were included in this prospective cohort study. Frequency of legume intake was estimated using a 3-month food frequency questionnaire, and incidence of CHD and CVD was obtained from medical records and death certificates. RESULTS: Over an average of 19 years of follow-up, 1802 incident cases of CHD and 3680 incident cases of CVD were documented. Legume consumption was significantly and inversely associated with risk of CHD (P =.002 for trend) and CVD (P =.02 for trend) after adjustment for established CVD risk factors. Legume consumption 4 times or more per week compared with less than once a week was associated with a 22% lower risk of CHD (relative risk, 0.78; 95% confidence interval, 0.68-0.90) and an 11% lower risk of CVD (relative risk, 0.89; 95% confidence interval, 0.80-0.98). CONCLUSIONS: Our study indicates a significant inverse relationship between legume intake and risk of CHD and suggests that increasing legume intake may be an important part of a dietary approach to the primary prevention of CHD in the general population.   AD Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1430 Tulane Ave, SL18, New Orleans, LA 70112, USA. jhe@tulane.edu PMID 11718588
  4. 2 TI The effect of fruit and vegetable intake on risk for coronary heart disease. AU Joshipura KJ; Hu FB; Manson JE; Stampfer MJ; Rimm EB; Speizer FE; Colditz G; Ascherio A; Rosner B; Spiegelman D; Willett WC SO Ann Intern Med 2001 Jun 19;134(12):1106-14.     BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease.   AD Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. PMID 11412050 3
  5. TI Fruit and vegetable consumption and stroke: meta-analysis of cohort studies. AU He FJ; Nowson CA; MacGregor GA SO Lancet. 2006 Jan 28;367(9507):320-6.     BACKGROUND: Increased consumption of fruit and vegetables has been shown to be associated with a reduced risk of stroke in most epidemiological studies, although the extent of the association is uncertain. We quantitatively assessed the relation between fruit and vegetable intake and incidence of stroke in a meta-analysis of cohort studies. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, and bibliographies of retrieved articles. Studies were included if they reported relative risks and corresponding 95% CIs of stroke with respect to frequency of fruit and vegetable intake. FINDINGS: Eight studies, consisting of nine independent cohorts, met the inclusion criteria. These groups included 257,551 individuals (4917 stroke events) with an average follow-up of 13 years. Compared with individuals who had less than three servings of fruit and vegetables per day, the pooled relative risk of stroke was 0.89 (95% CI 0.83-0.97) for those with three to five servings per day, and 0.74 (0.69-0.79) for those with more than five servings per day. Subgroup analyses showed that fruit and vegetables had a significant protective effect on both ischaemic and haemorrhagic stroke. INTERPRETATION: Increased fruit and vegetable intake in the range commonly consumed is associated with a reduced risk of stroke. Our results provide strong support for the recommendations to consume more than five servings of fruit and vegetables per day, which is likely to cause a major reduction in strokes.   AD Blood Pressure Unit, Cardiac and Vascular Sciences, St George's University of London, London, UK. fhe@sgul.ac.uk PMID 16443039
  6. . These observations have implications for dietary recommendations in patients in whom fructose malabsorption is suspected since foods that contain fructose may be well tolerated if they also contain glucose but may be less well tolerated if they also contain sorbitol (although sorbitol itself can cause diarrhea). Thus, it is the net amount of fructose that is important. . These observations have implications for dietary recommendations in patients in whom fructose malabsorption is suspected since foods that contain fructose may be well tolerated if they also contain glucose but may be less well tolerated if they also contain sorbitol (although sorbitol itself can cause diarrhea). Thus, it is the net amount of fructose that is important.
  7. Metabolic pathways of entry of (A) glucose and (B) fructose into the glycolytic pathway of the CNS. GK, glucokinase; KHK, ketohexokinase; DHAP, dihypoxyacetone; Gald, glyceraldehyde.
  8. Proc Natl Acad Sci U S A. November 2008 4; 105(44): 16871–16875. Published online 2008 October 29. doi: 10.1073/pnas.0809255105. PMCID: PMC2579345 Copyright © 2008 by The National Academy of Sciences of the USA Biochemistry Differential effects of central fructose and glucose on hypothalamic malonyl–CoA and food intake Seung Hun Cha,a Michael Wolfgang,a Yuka Tokutake,b Shigeru Chohnan,b and M. Daniel Lanea1 The brain, like the liver, possesses a unique set of enzymes that enables fructose to bypass the rate-limiting step in glycolysis and thereby rapidly deplete ATP in the hypothalamus The central administration of fructose rapidly lowers ATP, increases P-AMPK and P-ACC (acetyl-CoA carboxylase ), and decreases malonyl-CoA in the hypothalamus, whereas centrally administered glucose has the inverse effects.
  9. Proc Natl Acad Sci U S A. 2008 November 4; 105(44): 16871–16875. Published online 2008 October 29. doi: 10.1073/pnas.0809255105. PMCID: PMC2579345 Copyright © 2008 by The National Academy of Sciences of the USA Biochemistry Differential effects of central fructose and glucose on hypothalamic malonyl–CoA and food intake Seung Hun Cha,a Michael Wolfgang,a Yuka Tokutake,b Shigeru Chohnan,b and M. Daniel Lanea1
  10. Nutr Metab (Lond). 2005; 2: 5. Published online 2005 February 21. doi: 10.1186/1743-7075-2-5. PMCID: PMC552336 Copyright © 2005 Basciano et al; licensee BioMed Central Ltd. Fructose, insulin resistance, and metabolic dyslipidemia Heather Basciano,1 Lisa Federico,1 and Khosrow Adeli1
  11. Basciano et al. Nutr Metab (Lond). 2005; 2: 5. Published online Basciano et al. Nutr Metab (Lond). 2005; 2: 5. 2005 February 21. doi: 10.1186/1743-7075-2-5. Copyright © 2005; licensee BioMed Central Ltd. Circa il 50-80% dell’APO B dopo essere stato sintetizzato viene degradato. Il processo di degradazione è regolato da una proteina microsomiale, la MTP (microsomial triglYceride transfer protein) che è necessaria all’assemblamento dei trigliceridi con l’APO B100 ed alla secrezione delle VLDL Highly efficient inducer of de novo lipogenesis (high concentrations: unregulated source of acetyl CoA) In contrast to glucose, dietary fructose does NOT stimulate insulin or leptin (which are both important regulators of energy intake and body adiposity). Stimulated triglyceride synthesis is likely to lead to hepatic accumulation of triglyceride So, reduction hepatic insulin sensitivity, as well as increased formation of VLDL particles due to higher substrate availability, increased apoB stability, and higher MTP, the critical factor in VLDL assembly
  12. J Hepatol. 2008 June; 48(6): 993–999. Published online 2008 March 10. doi: 10.1016/j.jhep.2008.02.011. PMCID: PMC2423467 NIHMSID: NIHMS52684 Copyright notice and Disclaimer Fructose Consumption as a Risk Factor for Non-alcoholic Fatty Liver Disease Xiaosen Ouyang, MD,1* Pietro Cirillo, MD,1* Yuri Sautin, PhD,1* Shannon McCall, MD,2‡ James L. Bruchette, ASCP,2‡ Anna Mae Diehl, MD,3‡ Richard J. Johnson, MD,1* and Manal F. Abdelmalek, MD3‡
  13. Nutr Metab (Lond). 2005; 2: 5. Published online 2005 February 21. doi: 10.1186/1743-7075-2-5. PMCID: PMC552336 Copyright © 2005 Basciano et al; licensee BioMed Central Ltd. Fructose, insulin resistance, and metabolic dyslipidemia Heather Basciano,1 Lisa Federico,1 and Khosrow Adeli1