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The Role of Fructose in Non-Alcoholic Steatohepatitis

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The Role of Fructose in Non-Alcoholic Steatohepatitis nutrients Review Review ReviewReview Review The RoleThe of Fructose RoleTheTheThe of Fructosein RoleRoleRole Non ofofof- Alcoholic FructoseFructoseFructose in Non- Alcoholic ininin Steatohepatitis Non-AlcoholicNonNon--AlcoholicAlcoholic Steatohepatitis: Old Steatohepatitis:SteatohepatitisSteatohepatitis : Old :: OldOldOld RelationshipRelationship andRelationshipRelationshipRelationship New and Insights New andandand Insights NewNewNew Insights InsightsInsights Alessandro FedericoAlessandro 1,*,†, Valerio FedericoAlessandroAlessandroAlessandro Rosato 1,*,†, 2,Valerio3 ,† FedericoFedericoFederico, Mario Rosato Masarone 1, 1,1,1,**,†,†,†,†,†,,, Valerio ValerioValerio2,,3,† Valerio, Mario 2, Pietro RosatoRosatoRosato RosatoMasarone Torre 2,2,2,333,†,†,†,†,†2,3,†,,, MarioMarioMario 2, 2Marcello, Pietro, Mario MasaroneMasaroneMasarone Torre Dallio Masarone 2 22,2, ,, Marcello Pietro1PietroPietro, Mario2 TorreTorre,Torre Pietro RomeoDallio 222,,, Marcello TorreMarcelloMarcello 11, Mario 2, Marcello DallioDallioDallioRomeo 111, , Dallio, 1 Mario MarioMario 1 RomeoRomeoRomeo, 111 and Marcello Persicoand Marcello 2 PersicoMarioandand MarcelloMarcello Romeo2 PersicoPersico1 and 22 Marcello2 Persico 2 11 1 Department of Precision1 Department Medicine of, UniversityPrecision11 DepartmentDepartmentDepartment Medicine of Campania ofof of Precision,Precision PrecisionUniversity Luigi MedicineMedicine Medicine,Vanvitelli, of Campania,,,, UniversityUniversityUniversityUniversity University 80138 Luigi Naples, ofofofVanvitelli,of of CampaniaCampaniaCampaniaCampania Italy; 80138 LuigiLuigi Luigi Naples, Vanvitelli,Vanvitelli, Vanvitelli, Italy; 8013880138 Naples,Naples, Italy;Italy; alessandro. [email protected]. marcello.dallio@unicampania.italessandro.alessandro.alessandro.marcello.dallio@unicampania.it (M.D.); [email protected]@[email protected] (M.D.); [email protected] (M.D.); [email protected] (M.R.) (M.D.);(M.D.); [email protected]@unicampania.it (M.R.) (M.R.) (M.R.)(M.R.)(M.R.) 22 2 Internal Medicine2 andInternal Hepatology Medicine Division,22 andInternalInternalInternalInternal Hepatology Department MedicineMedicineMedicine Medicine Division, of andandand and Medicine, HepatologyHepatologyHepatology Hepatology Department Surgery Division,Division,Division, Division, of and Medicine, Odontostomatology, DepartmentDepartmentDepartment Department Surgery ofofof of and Medicine,Medicine,Medicine, Medicine, Odontostomatology, SurgerySurgerySurgery Surgery andandand and Odontostomatology,Odontostomatology,Odontostomatology, Odontostomatology, “Scuola Medica Salernitana“Scuola”, Medica Univer Salernitanasity“Scuola“Scuola“Scuola of Salerno, Medica”,MedicaMedica Univer 84084 SalernitanaSalernitanaSalernitana Salernitana”,sity Salerno, of Salerno, ”,Italy;”,”, UniverUniver University [email protected] Salerno, ofofof Salerno,Salerno,Salerno, Italy; 8408484084 84084 [email protected] Salerno, Salerno, Salerno,(V.R.); Italy;Italy; Italy; [email protected]@gmail.com (V.R.); (V.R.);(V.R.);(V.R.); [email protected]@unisa.it (M.M.); [email protected]@[email protected]@unisa.it (M.M.); [email protected] (P.T.); [email protected] (M.M.);(M.M.);(M.M.); (M.M.); [email protected]@gmail.com [email protected] (P.T.); (M.P.) [email protected] (P(P(P (P.T.);.T.);.T.);.T.);.T.); (M.P.) [email protected]@unisa.it (M.P.)(M.P.)(M.P.) 33 3 Liver Unit, Ospedale3 Liver Evangelico Unit, Ospedale Betania,33 LiverLiverLiver 80147Evangelico Unit,Unit, Unit, Naples, OspedaleOspedale Ospedale Betania, Italy EvangelicoEvangelico Evangelico80147 Naples, Betania,Betania, Betania, Italy 80147 8014780147 80147 Naples,Naples, Naples, ItalyItaly Italy * Correspondence: *[email protected] Correspondence:*** [email protected] Correspondence:Correspondence:Correspondence:; Tel.: [email protected]@[email protected] [email protected]; +390815666745; Tel.: +390815666745;;;; Tel.:Tel.:Tel.:Tel.: Tel.: +390815666745+390815666745+390815666745 +39-081-5666745 † These authors contributed† These authorsequally tocontributed† ††this TheseThese These work. authorsauthors authorsequally contributedcontributed contributedto this work. equallyequally equally toto to thisthis this work.work. work. Abstract: Non-alcoholicAbstract: fatty Non liver-alcoholic diseaseAbstract:Abstract:Abstract: (NAFLD)fatty NonNon-alcoholicNon liver---alcoholicalcoholic rediseasepresents fattyfatty (NAFLD) the liverliver result diseasedisease represents of hepatic (NAFLD)(NAFLD) the fat result overload representsrerepresentspresents of hepatic not thethethe fat resultresultresult overload ofofof hepatichepatichepatic not fatfatfat overloadoverloadoverload notnotnot due to alcohol consumptiondue to alcohol and potentiallyconsumptionduedue toto alcoholalcohol evolving and consumptionconsumptionconsumption potentially to advanced evolving and andandand fibrosis, potentially potentiallypotentiallypotentially to advanced cirrhosisevolving evolvingevolvingevolving, fibrosis,and to tohepatocel-toto advanced advancedadvancedadvanced cirrhosis fibrosis, fibrosis,,fibrosis,fibrosis, and hepatocel- cirrhosis, cirrhosiscirrhosiscirrhosis and,,,, andand hepatocellu- hepatocel-hepatocel- lular carcinoma. Fructoselular carcinoma. is a naturally Fructoselularlarlularlular carcinoma. occurring carcinoma.carcinoma.carcinoma. is a naturally simple Fructose FructoseFructose sugar occurring is is ais naturally widelyaa naturallynaturally simple used occurring occurringoccurringsugar in food widely simple industry simplesimple used sugar sugar sugarlinked in widely food widelywidely industry used usedused in linked foodinin foodfood industry industryindustry linked linkedlinked to to glucose to formto sucrose, glucose largelyto formtoglucosetoto contained sucrose,glucoseglucoseglucose to form to tolargelytoin form formformhypercaloric sucrose, containedsucrose,sucrose,sucrose, largely food largelylargelylargely in contained hypercaloricand containedcontainedcontained beverages. in hypercaloric food ininin Anhypercalorichypercalorichypercaloric and increasing beverages. food and foodfoodfood beverages. An andandand increasing beverages.beverages.beverages. An increasing AnAnAn increasingincreasingincreasing amount amount of evidenceamount in scientific of evidence literatureamountofamount evidence in scientific highlighted ofof evidenceevidence in scientific literature a inin detrimental scientificscientific literature highlighted literatureliterature highlightedeffect a detrimentalof highlighteddietaryhighlighted a detrimental fructose effect aa detrimentaldetrimental of con- effectdietary of fructosedietaryeffecteffect ofof fructose con-dietarydietary consumption fructosefructose con-con- sumption on metabolicsumption disorders on metabolic suchsumptiononsumptionsumption metabolicas insulindisorders ononon metabolic metabolicmetabolic disordersresistance, such as disordersdisorders disorderssuch insulinobesity, as resistance, insulin h suchsuchsuchepatic asasasresistance, steatosis insulininsulininsulin obesity, resistance,resistance,resistance,, and h obesity,epatic NAFLD steatosis obesity,hepaticobesity,obesity,- , steatosis, hhhandepaticepaticepatic NAFLD steatosissteatosissteatosis and- NAFLD-related,,,, andand NAFLDNAFLD--- relatedrelated fibrosisfibrosis asas well.well. AnAn excessiveexcessive fructosefructose consumptionconsumption hashas beenbeen associatedassociated withwith NAFLDNAFLD devel-devel- related fibrosis as well.related An fibrosis excessive asrelatedfibrosisrelated well. fructose An fibrosis asfibrosis excessiveconsumption well. asas An well.well. excessivefructose An Anhas excessiveexcessive beenconsumption fructose associated fructosefructose consumption has with consumption consumptionbeen NAFLD associated has been devel- hashas associated with beenbeen NAFLD associatedassociated with devel- NAFLD withwith NAFLDNAFLD development devel-devel- opmentopment andand progressionprogression toto moremore clinicallyclinically severesevere phenotypesphenotypes byby exertingexerting variousvarious toxictoxic effects,effects, in-in- Citation: Federico, A.; Rosato,Citation: V.; Federico, opmentA.;Citation:Citation: Rosato, and V.; Federico, Federico,Federico, progression A.; A.;A.;opment Rosato, Rosato,Rosato, to V.; V.;V.;and more progression clinicallyandopmentopment progression andseveretoand more progressionprogression phenotypes clinically to more to clinicallyto severe bymoremore exerting phenotypesclinicallyclinically severe various phenotypes severesevere by toxic exerting phenotypesphenotypes effects, by various exerting in- byby exertingtoxicexerting various effects, variousvarious toxic in- effects, toxictoxic effects,effects, including in-in- Citation: Federico, A.; Rosato, V.; Masarone, M.; Torre, P.;Masarone, Dallio, M.; M.; Torre,cluding P.;Masarone,Masarone, Dallio, increased M.; M.;M.; Torre,Torre, cludingfatty P.;P.; Dallio,Dallio, acid increased M.;M.; produc increasedcludingtion,cludingcluding fatty oxidative acid increasedincreasedincreased fatty produc stress acid fattytion,fattyfatty production,, and acidoxidativeacidacid worsening producproducproduc oxidativestresstion,tion,tion, insulin, and oxidativeoxidativeoxidative stress, worseningresistance.
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