748 J.Endocrinol.Invest.35:748-753,2012 DOI: 10.3275/8011 ABSTRACT. Backgrounds and aims: Weassessedtheassoci- ations between pancreatic fat accumulation and other fat compartments,includingliverfatandvisceraladiposetissue aswellasinsulinresistanceandothermetabolicabnormali- tiesinobeseindividuals. Subjects and methods: Westudied 42Caucasianadultswithobesity[20menand22women; meanbodymassindex(BMI)35.2±4kg/m 2 ],whohadnohis- tory of liver diseases or excessive alcohol consumption, in which subcutaneous, visceral, liver, and pancreatic fat con- tentswerequantifiedbyanin-opposed-phasemagneticres- onanceimaging(MRI)technique. Results: Comparedwithpa- tientsinthelowertertile(<5.6%,no.=15),thoseintheupper tertileofliverfatcontenthadmorevisceraladiposetissue, greaterinsulinresistanceandhadhighervaluesofBMI,blood pressure,triglyceridesandlowerHDL-cholesterolandadipo- nectin.Notably,pancreaticfataccumulationalsosignificant- lyincreasedacrosstertilesofliverfatcontent.Inunivariate analysis,thestrongestcorrelatesofpancreaticfatwerevis- ceral and liver fat contents (r=0.80 and r=0.54, p<0.001- 0.0001, respectively). Pancreatic fat accumulation was also moderately associated with insulin resistance and other metabolic syndrome features. However, when adjusted for age,genderandvisceraladiposetissue,theassociationsof pancreaticfataccumulationwithliverfatandothermetabol- ic abnormalities were no longer significant. Conclusions: Therearesignificantassociationsbetweenpancreaticfatac- cumulationandliverfatcontentaswellasinsulinresistance and other metabolic abnormalities in obese, but otherwise healthy,individuals.However,theseassociationsarelargely mediatedbytheamountofvisceraladiposetissue. (J.Endocrinol.Invest.35:748-753,2012) © 2012,EditriceKurtis INTRODUCTION Obesity represents a public health concern because its prevalencehasreachedepidemicproportionsworldwide andisassociatedwithanincreasedriskofcardiovascular eventsandotherimportantco-morbidities(1).Obesityis alsooftenaccompaniedbyalterationsinbodyfatdistri- bution (visceral vs subcutaneous fat depots) and by ec- topicfataccumulation.Thislatterphenomenonconsists of lipid accumulation in the parenchymal cells of multi- ple tissues, including hepatocytes, skeletal and cardiac myocytes and pancreatic cells, which results in chronic cellular dysfunction and injury, generally referred to as “lipotoxicity” (2). It is known that obese patients have more fat accumu- lated in their liver than lean control subjects (3). This pathologicconditionisdefinedasnon-alcoholicfattyliv- er disease (NAFLD). It encompasses a spectrum of dis- eases, ranging from simple steatosis to steatohepatitis andcirrhosis,andisnowregardedasthehepaticmani- festationofmetabolicsyndrome(3,4). Whilethepresenceofastrongassociationbetweenobe- sity and NAFLD is currently well defined (3,4), there are onlyafewstudiesaddressingtheassociationofpancre- aticfataccumulation,asdetectedbymeansofmagnet- ic resonance imaging (MRI), with either obesity or glu- cose intolerance (5-10). Moreover, there is currently a paucityofimagingdataontherelationshipsofpancreatic fat accumulation with liver fat and other fat depots. Recognitionoftheserelationshipsmaybeofclinicalim- portance as the pancreatic fat accumulation might con- tribute to the development of metabolic disorders typi- callyobservedinpatientswithNAFLD. Theaimofthisstudywastoexaminetheassociationsbe- tweenpancreaticfataccumulationandotherfatdepots, including liver, subcutaneous, and visceral adipose tis- sue, as determined by MRI, in a sample of obese indi- viduals, and to determine whether pancreatic fat accu- mulationisassociatedwithinsulinresistance(IR)andoth- er obesity-related metabolic abnormalities or whether thisassociationismediatedbyotherfatdepots. MATERIALS AND METHODS Subjects We studied 42 Caucasian adults (20 men and 22 women) with obesity(definedasBMI≥30kg/m 2 ),whoconsecutivelyattended ourobesityclinicduringaperiodof18months.Subjectshada meanageof47±13yrandameanBMIof35.2±4kg/m 2 (35.6 kg/m 2 formenand35.1kg/m 2 for women). Most women were inpost-menopausalstatus(no.=16)anddidnottakehormonal replacementtherapy.Weexcluded(a)subjectswhoconsumed excessiveamountsofalcohol(i.e.,>20gofalcoholperday);(b) those who had a prior history of diabetes, cardiovascular dis- ease, overt nephropathy and liver diseases (i.e., drug-induced liverdisease,hemochromatosis,autoimmuneorviralhepatitis); and(3)thosewhoweretakinganymedications.Therefore,none ofparticipantshadanyovertdiseasesotherthanobesity. Key-words: Liverfatcontent,non-alcoholicfattyliverdisease,obesity,pancreaticfat content,visceralfatcontent. Correspondence: G. Targher, MD, Section of Endocrinology and Metabolism, De- partmentofMedicine,UniversityofVerona,PiazzaleStefani,1–37126Verona,Italy. E-mail: giovanni.targher@univr.it AcceptedSeptember7,2011. FirstpublishedonlineOctober4,2011. Pancreaticfataccumulationanditsrelationshipwithliverfat contentandotherfatdepotsinobeseindividuals G. Targher 1 , A.P. Rossi 2 , G.A. Zamboni 3 , F. Fantin 2 , A. Antonioli 2 , F. Corzato 2 , C. Bambace 2 , R. Pozzi Mucelli 3 , and M. Zamboni 2 1 Section of Endocrinology and Metabolism; 2 Section of Geriatric Medicine, Department of Medicine; 3 Department of Radiology, University of Verona, Verona, Italy © 2012, Editrice Kurtis FOR PERSONAL USE ONLY