Thermic effect of food in hypothyroid rats.

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Thermic

effect of food in hypothyroid

rats

S lossa, t Lionelti, M P Mollica, A Barlelta and G tiverini

Departmed ofceieralind frvionnèrta Phys olosy, liivèBily ofN

(Requers for olrù db shoúld be addre$ed ro C Liver n, D pùrme o di Fis oloB a CeieÉ e erlAnb e ale, Via MezzÒcànnÒne 3, r30rr4 Napoli, ialy)

The regulatory and obligatory comp@ents of cephaLìc and g " r r o r n r u n r l p h J c . o f ! h ( r h c r m ' e l T e ' r o f l o o d lT t f vere measured in control aod hypotbroìd rats. A signifi cant dec.ease (P<0 05) in regùlatory and obligatory com-porerts ofcephalìc ard gastrointestinal TEF, after eithèr a control or energy-dense ra$I, wàs Íòund ìn hypÒthyroi.l ràts compaied with control nts. Our findings indìcàte ther

h)potlìyroìdnm js àsciated wth a deiieàsed thÈnnogenic rcsponsc to 1òod whìch contrìbutes to the redúced ene.gy exlenditure of \pothyroìd rats. Our results also $ggest that t.i-jodotlryronjre is involved in ùe regulatìon olpostprandial tbemogenesk directly as wef as through its nfluence oD p{drenùsic response and insulin rcleae. lounàl ol En.l.oinÒlast 11996) ta, 167 17a

It is wcl knowD that the acute increase in met bolic rute wliich occun after r neal, the thermic ellect of îood (TEF), has .wo distìnct pbases. The inìtial cephalic phue lasts about 30 mn1 aDd n indù.e.I by sensory stnnuhtions (Diúond a dl. 1985. Allard & Le3lanc 1988, LeBlanc 199r), rhe subsequent gasrointestìnàl phase n er?lained by the composihoo md t\e caÌoric content of the ingested nutrients (LeBlanc & Dìmond 1986). We have shown reccndy lhat in r.ts, as vell .s jn doss Qiamond & LeBl.nc 1987), the phases oITEF consist oî tvo coù1po-nen*: a regulatory component which is under the control ofrhe synpàthetic neNóús systen (SNs) as 1r s abolshed by propnn.nol (Livenni er dl. 1995), and an obligetory component not aflected by propranoÌol (Lìverini ./ dl. 1995). Wc have also shown ùat the resuÌalory component can play a role ìn preventìng the development of obeslty (Livennì (r dl. 1995).

Prevìous studies have demonltmted that TEF is rèlated to pr-ex(ting leveis of theraoge,lesls. In fact. úts wlrh high levels of themogenesa, súch as cold-àd,tted, hrcenhyroid and hyperphagìc rats, exhibit ao ioúease ú TXF (Rothwel et a|. 1982a, 1983, Roùvell & Stock 1983). On the other haDd. fdtins or obese rae wlich èxhibit low leveLs ofthenaogenesis shoù, r rdù.ed TXF (Rothvel er al. 19i11, 1982d, RÒthwell & Stock 1983). Since low levels of themogenesr ere ,lro chàr-actenstic of the hypothyioid state (Donner Deíllà & Marcum 1973, Guersey & Edelman 1983, Hryàshi & Nagasaka 1983), it vd ot intcrcs! to verify vheùer changes in TEF could contribute to the reduced energy expendìcure o{ hypothyroìd Fts. To this end we have mearurèd thè regulatory ànd oblìgatory .o,alonents ofthe

cephalic and gasrrointestin?l pheses ofTEF ln hypothyroid

Materials and Methods Akinók and e'pennefltdl desgi

Forty male wìstàr nts (Chàrles River. Calco, ltaly), veighing 60 + 2 g, vere used lor the experìments. HaÌf Òf the nts were made h)pot\yroìd by àdmitusrration of à 0 1% solutioD ofprolyltliourac (PTLr) ìn drìnkng water for 27 days; the remainder were used as controls. Àll mh werc given riee acce$ to a control diet dd water, and were nàintalned one per cage (in grid-bottomed caset at 2,1"C úndei an anlfìcial circadian 12 hÍght:12 h darknes cycle. Food intàke (corected íòr spiìàge) and body weìght werc medurcd daily. Animal care, housìng and k ing nrt the guidelires ofthe lt.lian Health N4inistry.

O\t gen consumptioD measurcments were perfomed as previousLy descnbed (Iosa et al. 1992, Ltu.nn eî a|. 1992). Brefly, o\t gen.onsùption was measured wìth an oxygerl consúraptiorl mónitor (Cotumbùs Insiuents, Columbus, Ohìo, USA) in a chamber àt 2,1'C. All rats werc allowed to adapt to the condirions for a minimun of 30 min befofe besrnDns ùe measurements. Values were taken o y when the aninals were resting.

Cèphàlic rnd gastroìntèstinal phases of TEF were measúied by úsùg two tèlt ueals, one compoed of a control diet (29% prorein. 10 ó% lipid and 60,1% carbo hydnte, J/r00J; 12 5 kJ metabolìzable energy/g) and the otrer compGed olan energy de6e dier (28% contiol diet, 39 5% lyophilzed meat, 17 8% butter, 12% alphacel,0 7% AIN vitamin nìx, 2% AIN nnDeraÌ _{mix, 9/100 $ com} poritìon=29% protein, 50% lipìd and 21% carbohydrate, loutnal Òl Endo.ùnolasy 11996) 114 r 67-1 7a O I 996 Journal ol Endo.r no osy Ltd rr,nted in oeat srtatn

168 s lossa and others Themic etlecr of faod in hypothyoid n's

J/100J, 1s 8 kJ netabolìzable energy/g). The latter dret ìs characrerized try a higher calonc content and by the presence ofa meat .dnponent which is among the Ravou4 most prèfered by nts (Naim et al. 1985). It wàs chùen because ofits ability to stimulate SNS actìuty a{ter both àcutc (Liverini ., ,1. 1995) and chronic (Ljverìni er al.

1994) administration. Measureúent oJ totdl TEF

On the 27th day the rats were starved îo. 16h froh 1700 hi at lhe end oldre fstins period, .àts were nlected vith sa$re. the fating resrng úetabolic ràre (R'MR) was meaiured aDd the vaÌues obtàìned seNed as baselirc vùucs in the calculation of total TEF.

CephÀlic TEF was measured in 6ve control and 6ve hworhyroid €ts by giving trem a smal potion (7 kJ; 0 56 s) ofa test meal conpsed ofthe .ontlÒl diei, wljle 6ve control and five hypothyroìd iàts weie glveo à smal poftìon (7 kJi 0 41g) of a tesr meaÌ compded of the energy-dense diet. we used very snaÍ neals (7 k) to minimize TXF due to digestion, .bsorptìon and sto.age of r o m . l o . ' o r o L h c p c . i b i l i ^ , 1 . p " r o ' , 1 - r r r . r . e r n oxygen consumllion could tre due to the tnovements ol the n* during eatiDg, the measurÈ,aenLs staÌted after the lats had completely erten thè test neaÌ. This Nas posible because the anoút of f6d glven was very sman (abou! 0 5 g): ìt took les rhàn 2 min to be ingested and then the iàts rapidly resumed the ìnitial resling daytime psition.

q r F r rnp end ol L,he m e a l . o 4 8 . , . o n n n p q u - $ r ' contiouously motritored for 30min. The tutegiàted increde in the 30-min penod vas calcúlàted using n\e castrointestinal TxF was neàsúied in fìve control and five hypothyiÒid ràrs by gìvìng them a ldger portron ofthe cÒnhÒl meal (35 kji 2 8 g), while five control and five hypothyroid nts were given à ldger portjon ofthe energy-dcnse neal (35 kJ; 22s). The rats àte the food ln aboùt 10 min. Oxygen consunltiÒn ùàs measúred every 10 min f o , r8 0 n i ì r f e ' . J . o ] . u n p , o , v " u e . o v e r 2 n i n u c r c takeD only whÈ,1 the aúúàls were restìng). The intcgated increase was calcúlàred úsing the tràpezoid method. Med\rtenent óf óblirótary 'l'EF

Three dalr later, the rats were ,gain stared for 16 h fron 1700hì àt the end of the 1àsting period the rats were injecred wìth propmolol (2 ms/100 s body weigho. the fasúng Rl{R was measured and the values obrained seÍed as baseline values in the calcuiatioh ofthe oblig,tory comp@ent of ceph.lic and gastrointestinal TxF. The

w e , e e p - r , r d a . , { e - n b e d ' b o \ e . Seúfl thyraid honÒne \erck

At the end ofTEF neasuremÈnn, rats were Ànesrhetized by i.p. i{ectìon óf chloial hydràte (40 mgl100 g body jaùnat ot En,ta.tinatosr \1ee6) 144, 167 171

weisht). bloÒd vas colected via the abdominal aona and the thyrùd state of the dimals ws monitored by úeasuiing serum lìee tri iodothyronjne (TJ and hù' iodoùyroDine (Tr) levels accoding to the ùethod of Rómell er al. (1978).

Data .re given as means+s.r.M. of lìve ditlerent mts. Statistical signiicance between the neàns vas exàdlned by nulti-way analysis o{ variancÈ (o y ftr údn efects) folowed by tlvo-tailed SrúdenCs I t?st. Probab,liry values le$ rhàn 0 05 were codìdered to indicate a significant

Dl-PrÒphn.lol wàs purchased ftom Sigm Chemicel Co., Sr Louis, MO, USA. Àlphacel, AIN mineral and vitamin mit were purchased Éom ICN Phamaceuticals Inc.. Costa Mcsa, CA, USA. Lyophìlized meat (Liomellin, Star s.p.a., Milano. Italt and butter (Lurpàk, Deúaik) were

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Fisure 1 Body weisht sain and tood rtake in contoL (O) aid hypoùyrod (a)rats. rhe vaLues arc reported as means+s!.M ol ùenty diflere.t rats. Valles of hypolhyroid rats are sisnifi.anty (P<00s) ditrerent compar€d with thos€ ofcontrol nts.

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Thermic ,.ffect af foÒd ih hypothyrcid àts s ossa and oth€rs t 6 ! 6

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Fieure 2 Body weisht _Bain and lood ntake in PÌU+saljneìreatad 1a) and PrU+fr reated (O) rals. Plu+saline lreated rar were given mU (01% in driÒkng water)and daily iftraperilonear injections of saline, whilè PrU+rr reated rats were Eiven PrU (0.1% n drnkinB water)and daiy fraperitonea .jections of rr (500 ng/100 g body weisht) for 27 days. fhe values are rcported

of aive dfe@ft rats. Values of food intake oa PrU+Tr treat€d rats a.e sicniiicantly (P<0 05)dffereft compared wth lhose ol PrU+salne reated rars fom lhe eiShrh dal

To rcst the inllúence ol dryroid homones on TEF. hypot\roidism was indú.ed in nrr by trearmenr with PTU. Tlie hypothFoid state of PTu-tr.ated r.ts was confrmÈd by ihe ìneduremenrs ofsetun-free Tj and Ta w h i c h w e i e 4 . 0 + 0 2 a n d 1 1 + 1 n g / l r e s r e . t i v e l y j n . o n Í ó l i r r ' "rd u- - trlov hc limr ù oe'e, Fu- ru Body weighr gaú aDd food intèke in conÍol and hypothyroid nts are shown n1 Fig. l. Control rars gaìned Nèigbt at a constant nte dunng the èxpenDental peliod, vhile hypothyroid nh saiied weighr dowly duins the fìrsi ten dayr and then stopped growìng. Food intake/ l 0 0 g b o , l y h . g h , i r é . o l g f l r r _" r d y l o . ' . r r n

+ S a l i n e + P r o p r a n o l o l Fiaurè 3 Fasring refinB meraboic rate (RMRI n controÌ (open baÉ) and hypothyroid (hatched batsl ràts afler saline or popranolo injectiof. Rats wère fasted for 16 h lrom I7oo h, ar the end ortlre fastinB period they wère irjeded wnh either erne or propranololand ihe fastins RMR was measure.l, Ihe vau€s af€ reported as mea.s+s€M of rwefty d fferenr rats. ,P<0 05 compared wnh conro rats. "P<0.05 cÒmpar€d wirh sa ine inle.red hypothyroid rals.

hypothyroid mts conpared with confol nts. fo deter nrine ifthe decrease ú fòod ìntake was dùe to a direct actìon ol PTU or to the decrease in setun thyrojd hotuone levcls, mts were trated with PTU plus à replaceneDt dose of T: (500 ng/r00 g body weight daily) or PTU pl$ salire for 27 dàys. Setun-free Tr levels of PTU+T3 Íeated rats were 3 0+0 1 ng/I. The results show t\at PTU exeÍs a difcct acrion o11 foÒd intake oily in the fist days oftreàtment (Fjs. 2) ln fàct, sraning Èom abÒut the eigìrlli day of treàh11ent, PTU+Ttr treared rats ate àn.l gained veight to a gieàter extent rhaD PTU+ sàline tieàted rats and to a simiìài exteDt as control rars (Fìgs 1 and 2). We thìnk trat food inrake was lower in the isr davs of pTU treatìnent becàuse of the birter raste of PTU supplemented water. Thus the rats drinkdd ear le$ until tliey get used ro rhe tasre ofPTU.

Faring RMR measurenenrs in corrrol dd h)?othy-roìd na afté. the injection of elther saline or propanolot are shown in Fig. 3. In saline injected Ér5, fastils RMR vas 12% lower in hpothFoid nts compàred wùh conrrol

. . . : p r o p r , .o l o , J F , , o , . . - c o . ' . ts, n rlr o- a.r in : \ r . n s R M R / - 4 J ) , ' l . ! o l . y r o r d 1 b ' . , r $ . ùitbout eliect ìn contról rats.

The Esults of the detemnnation of cephàtic TEF in contiÒÌ ànd lrypothfoid iàrs after tlie control or ( n ! r g v d è n é n J . / f ' 8 . 4 _{" . d} 5 \ ' Ì o q r r , p d i r r . r c r . -in RMR that reàches a peak value afìer about 10 m-in andreturDs to the piefeedinglevel afrer abour 30 min. The

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170 s ossA and orhers Ihemic effect af foorl in hypothyrcid iats

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Minutes after feeding

1 0 1 s 2 0 2 5 MÌnuies after teeding

administntion ol proptuolol significandy reduced TEF by about 60% in cÒnÍol rats and by about 80% ìn hypothyroid mts, àfler c@rol and energy dense ì É J . H } ? o r t y r o r d m b . h o i e d

" i 8 r u f i c r r r d - . * r i , ' TEF alier control or energy dense nleals (Figs 4a,. and 5d,,). Thn decrease wa due to a decrease ln obligàrory TIF measured in propmolol-injected rats (Figs 4ú,, and 5ú,,) as weú s in .egùlatory TEF caÌculàred ftom dìe ditrerence between total and obligatory TEF (Fìgs ,lù,. and 5ù.').

The addnisÍation ofa Ìarger test {neal to rats itrduced a sìgnilìcanr increase in RMR wlich-was nearured up to 180 mjn. The integated incrcse n1 RMR berween 30 and 180 min after meal cons!ùnption was tàken as repre seotatìve ofthe gutroìntestinal TEF. The administnúon of propranolol significantly iedúced TxF in control dd hypotliyrcid ELs (Figs 6ú and 7r). The obligatory and rcgulatory conponenr of TXF accounted lor about 45% ànd ss% of total TEF respectively in cont.ol ànd hypo-thyroid ats after control and energy-dense mears. ^ signincant decrede in total. regùlatÒry ànd obligàtory gastrointestinal TEF after conÍol (Fìg. 6) and cnelsy dense (Fig. 7) deaÌs was found in hypothyroìd rats compared with conbol rats.

ln this work we hàve measured ùe regulatory and oblìgatory conpoúents of TEF in the hypothyroìd state. wllch is a condìtión of low energy er?enditure Ponne( Denkla & Marcúm 1973, Guernsey & Edelman 1983. Hayashi & Neg$àka 1983), and we have found that fàsting RMR (Fig. 3). as weÍ d food ìntake and body weighr gàin (Fig. 1), decrcded in hypoth)mid

rats-we hrr r alo rea"rr"à :.h,,g R-MR Jf'er -he Inje oon olthe p-blocking agent propnnolol boù ìn control and in h)pothyroid nrs (Fig- 3). The results show drat there is e sighrncanr decrede in fdtins RMR only jn hypothyroìd mts. This finding coDntm previous obseúaÍons that hwothyroìd rats shov an increded à.tivity of the SNS (Henley dr al. 1991, Sjlva & LaDùberg 1991), which

Total Obligatory

RegllaÌory

I F F

T E F

T E F

Figurc 4 cephaic thermi. €ffect ol lood (TEF)in conirol (O, open baÉ) and hypothyfoid (a, hatched baB) rac alter a contro meal, (!) fota rEF time cou6e measur€d in saline injected rac. (b) Obigatory rEF time cou6e measured n propfanolol inteded rats (unbrok€n linet and regulaÌory rEF lime coure calculat€d fom the díerence behaeen tota and obLisatory lÉF (brokef ines), (c) ntegraled fEF caculated usins th€ tapezord method. Control and hypothyroid rats were injected with elther saine or proprarolol, the lan.8 rening metabollc rate was measured and lhen the rals were fed a 7kl test mealcomposed ol rhe conùol diet, after the end ol the mea, orySen consumption $ r , , o r 1 1 o u . l , m o n i r o _{" d} b ' 0 m . . \ ' . c ' r ' F r t p o ' d d means+s.rM of live d fferent rats. 'P<0'0s compar€d wnh .oftro

Thermic effect of faorl in hypothwaid nE s rossA and oihen 1 7 1 .9 0.6 E 2 E 0 2 !

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confibures by aboúr s0% to fàr]ng RMR ln hypothyroid nrs (Fig. 3). The increased SNS àcdvity is .oúsider.l to be an.ttempt to maintin nomàl body tempentuie (S và 1993), expeciaììy jn rats kept at f@n temperature (2,1"C) a ìn this study. In agreement with tlis, sevenl autlios have lourd that brown adìpose tissue. the majn site of fa.ultative thennogènesis. shows some characteristics otits rectulted state in hypothyioid rats (MoÌy cr al. 1981, Pa* et al. 1989, Dìckeî et dl. 1992). Howeler, hypothyroidisa induces à reduced tìsue responsivenes to SNS stìmuli (Dicker e, al. 1992) due to x reduced number óf p-receptors (Bilezikian & Loeb 1983) as \{cll as to pdt-re.eptÒr dÈfèch (Dinjtnadi' .t dl. 1991, Pncyk & Slotkin 1992, wàhrenberg .r dl. 199,1). Therefore, the inùeased SNS àctivity r 11ot completely eFecíve D màintaining nom.l R'MR (Fig. 3) as well as nonnal córe temperature (Park er dl. 1989, Abelenda & Púerta 1990, Heùley .r al. 1991).

We measured cephalic TEF after nvo dilferent meaÌs codpded of eùher .ùtro1 or energy-dense dìeis. Tbe resúlts show that hypothyroi.tisn elicits a si$ificaDt decrease in cephalc TXF whatevei the meaÌ (Figs ,l ànd 5). Thn dccrease is due to a reductìon in both the obligatory and fegulatory componcnts of TtF. The reduced ob1ìgatory component of ceplialic TEF can be explained by the virtual absence of circulatrng r\roid h , r , : - i - - . , n l - ) p o , 5 ) , o , d 1 6 I n [ ' . _{" ì} : c - e , . r

r p ì r . î r I h . . 1 . l _{b . - ' ò . - d " r e l e e d s , ì " ,} (T<othwel et dl. 1982ú) and rigs (Dauncey & Morovar

l r o l ì . J h o u g l h c . x , - . , r o w h i ì ' l - I n F J . - I n thyroid hormoDc could conrribute ro TEF is ar presenr unclear. It has aho been slom that feeding induces an Èàrly plà\na turufin nrcrease lde latls 4 al. \977, Diú1ond & LeBlan. 1987), whi.h in tum stnnùhtes SNS àcnvity oliamond & LeBlànc 1988). Sin.è hypothyroidìsm n charàcrenzed by a redúcnon in both plasma insuli! lcvcÌs and peàk plasma iisulin respoise to B l , , ù - l o J d l o e t , r o 8 , . l - e d e . r e . . r a o b l i s r o D I E I cÒlld alsó be due to àn inpàimÈnt in insulìn response

The reduced È$Jatóry conponent of cèphaljc TEF colld be due to the dedeased tissúe iespoúslvenes to SNS

Figùrè s Cephaic thermic efect ol lood (TEF)in conlúl (O, open ba6)and hypothyroid (4, hat.hed baB) rats after an e n e € y d e n s e m € a . la l l o t a l f E F t m e c o u 6 e m € a s u r e d i r ' salne l.jected rars. (bl OblgaroryÌEF rne cou(e measured in pfopranolol-inje.ted rats (ufbroken lines)and regùlatory rEF time cou6e ca.ulat€d from th€ dlference betlveen tota and obisatory TEF (broken inet. (c) nl€sral€d îEF cacllated usins th€

lrapezod melhod Controla.d hypothyroid rats were inj€cted with ejther saine of propranolol/ the farl.S resiing metabollc rate ws medured and th€n the rats we.e fed a 7 kl test mea cómpóscd ól an anergy dènse diet, afer lhe end of the mea, oxy8ef consumption was coftinuousy monitored tor 30 mf. Values ar€ reported as means+stM of live d fferent rats. 'P<0.05 compared w th.ontrol Grs

f E F

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T E F

172 s ossA and others Themt effe.t af foad in hypothytoi.l ers

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risure 6 lhe th€hic efted of food (TEF) in coÒtrol (O, open ba6) and hypothyroid (a, harched bar) raG after a conÚolmea. (a)ÌotalrEF time couue and intqrated rEF measuf€d ln sallne-lnje.ted rats. (b) ObiSatory rEF time couu€ and integrated rEF measured in propranoLo 'injected rats. (.) Resulalory IEF tlme cou6e and ntesfated rEF caculat€d lóm the difference between rolaland obligarory TEF. Contro and hypothyrod fats w-ère nje.ted with eilher saline or proprano ol, the larfs restins merabollc rate was measured and then the rats wer€ fed a 3s kl ter meal .omposed of a contro diel aft€r the end ol the mea, oxysen consumpton was contnuously mon toÉd lor I80 min. Values are fepored as means+s!M ol iive dlffere.t rats. 'P<0 05 compared with

found in hypothyroid úts (Di.ker s, dl. 1992), as well as to a lower SNS stjmúlation caused by t\e ìmpùed insulin response. It should be noted that hypothyroidism also abolishes the increde iù tlie regulatory comporent ol cclhalic TEF induced ìn control nts by an energy-dense meal (Fis. s).

louhat oÍ En.laùtnalosr 11996) ua, 167 17a

we have also measured rhe pùrynndiaÌ inci$e ú RMR after a lùser meal (3s kl) (Figs 6 and 7). ìlhen companns TEF measured after the smaller and the larger mcal, itwas Íòund that the increase dunng the lìnt 30 min was comparable, in agleement wùh the finding that cephali. TEF is irdependent of meal si,e (LeBldc &

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Ihemìc effect of foad in hypothytoid ftt: s rossA and others 1 7 3 1 7 = ; . : 0 . ,

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risure 7 lhe thermic effect ol lood (TEF) in control (O, open ba6) and hypothyroid (4, hatched ba6) rac alter an ener8y denre meal, (a) rota ÌEF time course a.d integrared rEF measured in saine-injecled rats. lb) Oblisatory ÌEF time course and integnted rEF measured in proprano olinjecr€d Éts. (.) R€sulatory-fEF tme course and int€srated fEF aculated from the diflerence between totaland oblgalory fEF. Contol and hypothyroid rais were njectéd with eilher saline or prcpranolo, the fastins r€sling metabollc rate was measurcd and then the rats were fed a 3s kl test meal composed of an enersy'd€ns€ diet after the end Òl the heal, oxygeó consumptoÒ was continùols y monltored lor 30 min. Values arè réported as meafs+sÉM ol liv€ difierent rals.'P<005 compared with contro rats.

Diamond 1986, Allàrd & LeBlanc 1988). The integated postpràndiÀl ìncrease in RMR between 30 md 180 mir after the larger meal wd taken as .epresentatìvè ofthe gastlointestinal TEF. The .esults show that hpothy-roid4n sigrificandy deùeases both the regulàtùy and the oblig2tory componenr whatever the meal The above decrease cànnot be attributed to changes in food

.bsorytìon since lreliminary experiments have shom that food absorption rs not reduced in hypothyroid rats. How-ever, we cannot exctúde the pùsibrliry that the dedeased TEF foúnd ú hypothyroid nts could be due, at leasr in pan, to delayed food absorytion.

In conclusion, our findìngs indicate that hypothyroidisn is a$ociated with a decreaed themogenic response to

174 s LossA and othefs Theni. effe.t af t'aod rn htpothvard Bti food whicb contrìbutes to the re.{ùcÈd enèrgy expenditurè

.A.cknwledgement

This work was suplo.ted by MLIRST.

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$/ renbery H, We.nlùnd A & Aner P 1994 Adre.Èry. rÈgdÍion of lipolysis in fr .ells fidr lryFerhyrcid rnd hypodryrcid pÍienh hrnd ol CLitial Eúadìnrlosy asd Múrbrli:'n 7a a9B 90r.

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