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1、0013-7227/03/$15.00/0Endocrinology144(6):2201–2207PrintedinU.S.A.Copyright©2003byTheEndocrineSocietydoi:10.1210/en.2003-0288Minireview:LipidMetabolism,MetabolicDiseases,andPeroxisomeProliferator-ActivatedReceptorsCHIH-HAOLEE,PETEROLSON,ANDRONALDM.EVANSHowardHughesMedicalInstitute,Gen
2、eExpressionLaboratory(C.-H.L.,P.O.,R.M.E.),TheSalkInstituteforBiologicalStudies,LaJolla,California92037;andDepartmentofBiology(P.O.),UniversityofCalifornia,SanDiego,LaJolla,California92037Lipidandcarbohydratehomeostasisinhigherorganismsisfunctionsandthetherapeuticpotentialoftheserece
3、ptors.underthecontrolofanintegratedsystemthathasthecapac-PPARpotentiatesfattyacidcatabolismintheliverandistheitytorapidlyrespondtometabolicchanges.Theperoxisomemoleculartargetofthelipid-loweringfibrates(e.g.fenofi-proliferator-activatedreceptors(PPARs)arenuclearfattybrateandgemfibro
4、zil),whereasPPARisessentialforacidreceptorsthathavebeenimplicatedtoplayanimportantadipocytedifferentiationandmediatestheactivityofthein-roleinobesity-relatedmetabolicdiseasessuchashyperlipid-sulin-sensitizingthiazolidinediones(e.g.rosiglitazoneandemia,insulinresistance,andcoronaryar
5、terydisease.Thepioglitazone).RecentevidencesuggeststhatPPARmaybethreePPARsubtypes,,,and,havedistinctexpressionimportantincontrollingtriglyceridelevelsbysensingverypatternsandevolvedtosensecomponentsofdifferentli-low-densitylipoprotein.Thus,uncoveringtheregulatorypoproteinsandregu
6、latelipidhomeostasisbasedontheneedmechanismsandtranscriptionaltargetsofthePPARswillofaspecifictissue.Recentadvancesinidentifyingselectivecontinuetoprovideinsightintothepathogenesisofmetabolicligandsinconjunctionwithmicroarrayanalysesandgenediseasesand,atthesametime,offervaluableinfor
7、mationfortargetingstudieshavehelpeddelineatethesubtype-specificrationaldrugdesign.(Endocrinology144:2201–2207,2003)LIPIDSAREESSENTIALforenergyhomeostasis,repro-drome,orsyndromeX,whichreferstopatientswhoareductiveandorganphysiology,andnumerousaspectsinsulin-resistant(hyperinsulinemic)
8、,dyslipidemi
