Effect of a high-fat diet on energy balance and thermic effect of food in hypothyroid rats.

European Journalof Endocrinology (1997) 136 309-31s tssN 0804-4643

Effect of a high-fat diet on energy balance and thermic effect

of food in hgrothl,roid rats

Susanna tossa, Maria Pina Mollica. Lillà Lionetti. Antonio Barl€tta and Giovanna Liverini Diptttinento di Fisi.Ìoljia Cehùdle ld Anbiútak. Univflta di NoÌoli. Vit Mezzacannahe 8, t'801 31, Napolì, Ihltl

(Can$lahtunce sltould b. kùlessetl ta G Live{nl, Djpdttikt.nto dl Pisiolo\iù Genetule ed Anbientùle, Vìo Mezzo.anhau 8.1'80131, Napali, Itala)

I

I

Abstlact

We have cdried out measùements of energy balance in hypothFoid rats fed a Ìow-lat or a his}l-lat diet for eishteen days. We have also measùed cephalic ùd processins themic eflèct oi lood (TEF) { tef a low'lat or a hish-fat meal.

Body lipid gain, carcass Ìipid content and gross eliciency were signilicantly (P < O.O5l hisher iD hypothFoid rats Ià1 a highjat diet compùed with hypothFoid rats fed a loFfat diet, while netabolizable enersy iDtaÌe ùd energy expenditure remajned unchdsed. CÉphalic Tll after a low-lat úeal was significanrly (P < 0 05) lower in hylothyroid rats led a high'lat diet ompeed with hypothroid rats led a low lai diet, while it was signilìcantly (P < 0.05) higher .ì1ìer a high-fat meal than ater a ìow l.it meal in hrpothyroid rats fed a hish lat diet. No signiffcmt vdiatioD was found in pfocessing lEF ater a low-fat or a high-tat meal.

Our resulîs indicate that hylolhyroid rab are unable to develop increased energy expenditùe dd increased îEF in response to a high-fai diet.

Eurcpean laurnl oÎ EndÒcún lorJ 136 309-3Ì5

Introduction

It is well knor|In that thyroid hormones rcguÌate energy melabolism: hypedhyroidism .esults in large increases in netabolic rate (1, 2), whereas hypothyroidism causes a decrease in energy expenditure (3, 4). Thyroid hor' - ù n e r have aì.o been inrolved In rhe lhemogenic response lo hyperphagia and food ingestion. In fact, a signiffcani increase in lhyroid hormone serum levels occurs in hyperphagic mts exhibiling diet induced thermogen€sis (DIT) (5. 6), as well as after food insestion in mts (7) and pigs (8). we have pr€viously sbown that rats fed a hish-fat diet, Ìvhich exhibit high circulating lri iodothyronine (Tr) seruln levels (5), over-eat but resist becoming obese lhrough a sympatheticall]-mediated increase in enersy expenditue (5, 9). The above increase in energy expenditure is dùe not only to a chronic iùcrease in fasling resting metaboìic rate (RMR), bùl also to aù increase ir the acute thermic cfiect of lood (TEF) (10). On the other hatrd, we have Iound that hypothyroid rats show a decrease in both RMR and TEF (1Ì).

In view ol these observations, it was considered of int€rest to investigate whether the adminishation of a high-fat diet io hypothyroid rats was able to induce adàptive responses capable of preventing excess energy deposilion as it does in euthyroid rats (5, 9, 10). To this purpose, we have carried out energy balance measure-ments in hypothyroid rats lèd a low-fat or a high-fat

o 1997 SoÒiely rór thè Eubpéan Jounalof Endocdnoloqy

diet. In addiiion, we have measured cephaìic and processing TEF after a low-fat or a high-fat meal.

Materials and methods

Animals anil expefimental ìlesign

Forty-five male Wistar rats (Charles River, Calco, Como, Italy), weighing 60 :t 2 g (about 27 days of age), were made hypothyroid by adminislration of propyìthiouracil (PTU. 0'1% in drinkins water) for Ì2 days. on day 13, ffve rats (Bo rats) were killed for the determinatioù oithe initial carcass energy content and serum free Tr (12) using a radioimmunoassay ldt, while PTU treatment continued in the olher iorty rals. Twen5? rats were used as controls and were fed a low-fat dict for eighteetr days (Mucedola 4RF2l, Settimo Mílanese. Mllan, Itàly; p€rcentage of total m€tabolizable energy: 29 protein, 10 6 lipid and 604 carbohydrate, _{l/l; 15 88k1 cross} enersy/s). The other twenty rats were fed a high-fat diet lbr eighleen days 128% stock diet, 39 57o lyophilized meat, 17 8'/o butt€r, 12% alphacel. 0 7% AIN vitamin mlll, 2% AIN mineral mix, g/$ percentage of total metaboÌizable energy: 29 protein, 50 lipid, 21 carbo-hydrate,14; 19 85kI sross enersy/s). The laiter diet is characterized by a higher fat content and by the presence of a meat component which is among the flavours most prelerred by rats (13)i it was chosen

I lli .t /osn dd or,rds

be.ause ol ils àbilily to stimulate sympathetic nervous systcm activi5, after both acute (10) and chrcnic (5, 9) admlnistratlon. All rats wcrc given lree access io lbod and n'ater and rvere mahiained one pù cagc lin grid-bottomed case$ at 24"C under an artiffcial cLcadian 12 h lishtrl2 h darkness cycle. Animal càre. housing and hillirg mel the guidelines ot the llalian Health Ministrtt

Oxygen consumption was mcasured rvith an orygen consumptionmonitor(Columbuslnstruments. Columbus, Ohio, USA) in a chanber al24'C. All rats were allowed to adapt to the conditions for a minimum ot lomin before beginning the measurements. Valucs $rer€ taÌ(en onÌy when the animals were resting.

Me.rsut'ement ol TEF

Cephalic and processing phases of TIF wcr€ measured by using two test meals. one composed oi the low-fat diel and lhe olher composed olihe high fat diet. Toúdl ?EFAlter Ì5 days ofdiet tr€atmeni. the rats were staÌved for Ì 6 h from Ì 700 h. At thc cnd of the fasting period, rats were injecied with saline. fasting RMR was meàsured and the vàlues obtained served as baseline valu€s in lhe calculation ol lolal TER

Cephalic TEF was mcasurcd in ffvc hypothyroid rats fed a low-fat diet and fir'e hypothlroid rats fed a high-fat diet by sivins theù a small portior (7 kl metabolizablc ene|gy; 0 56 g) ot à lest meal composed of the low-iat diet, $'hile another lìve hypothyroid rals fed a low lal diet and ffve hypothyroid rats fed a high-fal diet were r i \ ( n a " m a l ì p o . r o n l : k l m c . . b o l a b ì , . ì c r ! y n 4 4 g ' of a test meal composed of the high-fat diet. Oxygcn corsumption was cortinuously monitored for 30min alìer the rai had completely ealen the test meal àod had resumcd the initial rcsting daytimc position. The integrated increase in the 30-min pcriod was cdlculated using the trapezoid method. The abovc procedure has been previously used to measuÌe cephalic TEP in rats (14)i in lAcl, ihe use ol very small portions of food minimizes TEF due to digestion. absorption and storagc ol food and allows measurement of the cephalic phase of TEF. r.hich ls independenl of lhe meal si,e ( 14, 15).

Processing TEF was measured in Iìve hypolhyfoid rats fed a low-fat dict and ffve hypothyroid rats led a high-fat diet by giving thcm a largcr portion of the low-fat meal (35kI metabolizable encrgy: 28s). while anolher five hypolhyroid rats fed a low fat diet and ffve hypothyroid rals fed a high-lhl diel were givcn a laÌscr portion ol thc high-fat meal (3s kl metabolizable energy: 2 2 g). The rats at€ thc food ln about 10 15 min. Oxygen consumption was measured e v e r y iO m i n l b r 1 8 0 m i n atter meal consumption (valu€s over 2 n1in lver€ tahen only when the aninals rÀrcrc rcstinC). Thc intcgmted increase ft'as calculated using thc trapczoid method.

tuRoÙjAN louÌN,{r of rNDocrx\olocY oee i) r 16

O b l i g d t o r ! T L f T h t e e J d i \ ' a r . r h r r r r ! u e r e lsuin starved for 16 h ftom Ì7.00 h. At the end ol the lasiing period lhe rats were injected with propranolol (2 mg/ ÌOOg body weighl), Iàstins RMRwas measuÌed and thc values obtaircd served as baseline Íalues in ihe calculation of the oìrligalory componenl oi cephalic and processing TIE Thc measuremenls were repeated as described above. Cortrol experiments showed that lasling RMR in rats treated with propranolol dld not chang€ in any ol the rats durins tie experiments.

Encrgy b alance measrrre,m€nts

Body lr'eighis and food inlal(es were mo tored dally to aÌlowcalculations of ìrody weighl gain dnd gross eners]. intake. The faeces were also collected daily for energy contenL measurements,

Digeslible energy inlake (takinsinto accountthe food spiilage) was obtained by subtractiùg lhe enersy measured in the faeces from the total energy intake as measured from daily food consumption. Metabolizablc energy inlake s'as exsessed as dlgeshble eneryy intake x 0 96 (16). The gain in enersy during the 18-day pcdod oldietary treatment ivas oblàioed by subtractins the energy content ol thc Bo group from ihat of each of the tn'o er'perinental groups. At thc cnd of TEF measuremenh, rhe animals s'ere killed by decapltatior. Aitcr gut content remo!,al, lhe carcasses were aulo clavcd, chopped into snall pieces, thoroushìy mixed, and hoÌnogenized in $'atcr (volumes equal to trùice lhe cafoass weisht) lvith a PoÌyhon. Samplcs of homo-genates as well as sanples of faeces $'ere desiccated into a dry poi'\der lron which small pellets (alrout 200ms) lvcrc made. The energy content ol lhe pellels and the gross energy contcnt of the low-fai and high'lal diets were measured with a I'arr adiabatic calorÌmeter caliìrraled with dry ben,oic acid standard. Hneryy expenditur€ was calculated from lhe difference beiween mctabolizable energy intake and energy gain. Gfoss elEciency n'as expressed as pcrccntage of ùetaìrolizable enersy intake stored as body eìergy. Carcass Ìipid .onienlwas measured accordins to the method of Folch et tr|. lI7).

Stafisfi6

Daia are given as means:l:srr ot lìve different rats. Statistical signifìcance belween the

cxamined by t\rvo-tailed Studerl's I lesl or by Lwo way analysis of vaÌiance (onÌy for maln cffects) followed by tivo lailed Sludent s t test. I'robability values less than 0.O5 rvere considered Lo indicate a significant difterence.

MaterÍals

u. Propranolol was purchased from Sigma Chemical Co., Sl Louis, MO. USA. Alphacel, AIN mireral and vitamin mir ù,ere purchased trom ICN t'harmaceuticals

luRoPrìAN loù{NAL Orì D\DOCRTNOLOCT 11997t r16 l\tpathltol]ljsn and hishlnt diet 3II

Table 1 Energy balance measurèmènts in hypothyroid rals led a owjal ora highlal diet. Values are the meansl s EM. oi 20 difierenl rals and refer io the ùhole period ol detarytrèatment (18 days).

Low-Íal High-fat

rniriarbody weight (q) Body weight gain (g)

lMetabo izable energy inlake (kJ) Body energy _{san (kJ)}

L pid gaii (g) (kJ)

Carcass llpid conlenl (%) Energy expendilure (kJ) Grcss etriciency ('/.)

Fasl nq RMR (mmol O,/m n x ks" '') Propranolol-lnjecled rals 9 3 a 3 1 4 7 4 1 1 0 2 3 5 3 1 4 9 1 6 2 1 1 5 1 5 2 1 1 1 l l 1 2 2 ! 3 1 S 1 6 : r 5 8 323 ! 49' 0 4 2 t 0 0 2 Gross efticienry: body èrergy gar/melaboizabe èrergy inlakè.

" P < 0 05 comparedwith hypolhyrold rats led a low-fat d et (Nvolailed Studenl's

Inc.. Costa Mesa, CA, USA. Lyophilized meat (LiomelÌin, Star s.p.a., Milano,ltaly) and buiter (l,urpak, l)enmafh) were purchased

localìy-Rcsults

]'he hypolhyroid stale otrals at Lhe beginning ot.lielary lrealment was conffrm€d ìry lhe measurements of L r n d p r . c r d b e s e r L r m ì . \ e ì s o t Ì c . T , i n B o ra r . .

Tablc Ì shows the results of energy balance measuÌements ill hypothyroid rats ted a lon' fat or a hish fat diet. Mear initial and ijnal body weishls werc nol signilìcantly differenl beiween the two groups, yielding a daily body weight gain of about l 5 g in both g r o u p \ . I h( r. w.re no \rgnrfi, a n t d i l h r e n , n s n metabolizable energy irtake and energy expendilure belween hypolhyroid rats fed alow fai or a high ial diel, although energy expenditur€ tends to be low€r. On the other hand, body eneryy and lipid galn as wcll as'/o carcass lipid content ol hypothyroid rats fed a hlgh-fat diet were sisnificantly hisher (+26%, +99"1, and +10'1, respectively) lhan those ol hypolbyroid fals ted à low Iirt diel. Consequently, gross eliìciency was signilìcan y higher (+2Ì'l"1 in hypothyroid rats fcd a hish-fat dict than in thosc fed a low-fat diet. Finallr fasting RMR was the same in hypothyroid rats lèd a low tat or a hish tal: diet, boih in saline injected and in pfopranoloì-injecled

The results of the determination of cephalic TEF in hypothyroid rats led a low-fat or a high-fat diet alter low-fat and hish fat meals are shown in !'igs 1 and 2. 'lbtal _integraied 'l-EF _{afler a low Int meal was signilì} cantly lower in hypothyroid mts fed a high-fat diet compared with thosc fcd a lon-fat dict (!is. 2). This decrease $'as due to a decrease in facultatiÍe TEF calculated irom the difference betÍ€en total and oblisalory 1'EF, while no varialion was found in obligatory 'L'F.l meàsured in profranoìoì injecred rats

(Fis. 2). On the other hand. no slsrificant variation in cephalic lH!' atler a hish fat meal was iourd in hypothyroid rals led a high làt diel compared with rhose fed aÌow'fal diel (Pig.2).In ad.lilion, cephalic TEF after a high-fat mcal was slgniffcantly higher than alter a lowfat meaÌ in hypothyroid rats fed a high-fat diet but nol in those lèd a kìwlal diet. lhis increase was compl€tely due to an incr€ase in facùltaliveTEF (Fig. 2). Postprandial increase in RÀrlR measured for 180 min after the end of a 35 kl tcst mcal is shown in Fig. 3. The integrated increase in RMR between 30 and Ì80min $'as taken as reprcsentatiÍe ofthe processins'IEF and is shown in Fig. 4. No signifìcanl varialion ú'as found in total mE although TEF alter a high-fat meal iends to ìre lower than that after a lorv-fat mcal. A signiffcant decrease in oblisatory :lì!' after a hish-fat ìneal compared ivilh TEF after a low làl meal was tound in both groups ol rats (Fig. 4). In addilion, a signilìcant decrcase in the obligatory componenl (lig. 4) and an increase in the facultativc componcnt (Iig. 4) of processins lTF after low-fat and high-fat meals was lbund in hypothyroid rats lèd a hish-fat diet compared $,ilh lhose fed a low-làt diet.

Dis€ussion

In ihis work we have cdrried oul energy baLance neasuremenls (Table 1) in hypothyroid rats lèd low lal or high'fat diels. The two grolìps ol rals were consum ing approximately the same amount of cncrgyi howcvcr, hypothyroid rats led a hish-fat diet gained signilìcantly more body energy as Inl and exbibited higher carcass lipid content than rats f€d a lo\'rlfat diel. ^lthough cncrgy cxpcnditurc $'as not signiffcantly altered, gross efffciency was higher in hypothyroid rats ied a high-fat diet than in those fed a low-fat diet (TabÌe l). The incrfts€d emciency of hypothyroid rais Ièd a hieh iàt diet presumably resuìis from lhe reduced energy cost ol

0.20 o . l 5

rninutes

after feedrng

Figuré 1 CgphalÌc TEF after low{at and hlghfat meals m€asured in hypothyroid @is led a lowjai (o) or a hishlai (o) dier. (A) Tora -ÍEF time course measured in saLine-injected rals alter a low-fal meal. (B) Obligalory TEF time.ourss measurod in propranolol-injecled rats (unbroken line) and lacullalivelEFtimecou6e calculaledfiom lhe difference between ioialand obligatoryTEF (dofied line) aiter a lowlal meal. (C) TotalTEF limscourse measured in saline-inj€cted rats aîera highlal meal. (D) Oblisalory rEF iime cource measured in prcpranolol-injected fals (unbroken line) and lacLharive TEF rime couce caculared lrom the difior€nc€ betwsgn loìaland oblÌgaloryTEF (dotled line) afler a highlal meal. Values are reporled as meansi sÈ M oi iive diilerent Éts.

l12 J lossd ard olú.rs

low-fat m€.l high-lat m€al

HYPOTHYFOID ÀATS FED A LOW-FAT DIET

EUROPFTN IOT]RNAL OF BNDOC NOINGY O99I T36

',= _0.10 E g _o.o5 A P o o o o = 0 . 1 s

E

lo{-fat n.àl high-tàr hèal HYPOTHYROID RATS FED A HIGH-FAI DIEÍ

FiguE 2 InlegÉied cephalic TEF aiter lowjat and highlal meals Ìn hypoihyroid rars led a low lar ora high-latdi€l, lnteg€redlEF over rhe 30 min pèriod was calculaled using lhe iÉpezoid mèihod. values are report€d as means 1 s E.M. of live diflerent ats. 'P < 0 05 compared with hypothyroid rals red a lowJai diel (lwo way analysis of vanance tolLowed by nÀo-railed studenfs

l-lesl). "P<0 05 @mpared with IEF after a lowjai meal in hypolhyroid rals led a high-fat diei (tlvGway analysis of vaÍance folÌowed by lwotailed Sludenl's

E Torrr rEF E obri!.rory TEF

sùrepN lorRNÀr or DNDocRrNorocY i r 997t 136

020

EDìthlnidisù aùJ hish-ld 'ia fI]

0.25 o20 0 . 1 5 0.05 . q

E

o

E

Iat synthesis. Itr fact, in rats consùming standard laboratory diets almost all of the body fat will be synthesized de ,ol'o from glucose, with a relatively high energy cost (o 36 k]/kl fat deposited) (18). When the level of fat in the diet is increased body fat is derived directly from dietaÌy lipid, with a much lower energy cost (0.16kl/kl fat deposited) (18). In h,"othyroid rats, the energy saved in this way is not dissipated but stored as fat. The above results are different ftom those previously obtained by us on euthlroid rats (5, 9, 10).

o2a

o.oo

In fact, we have found that euthyroid rats fed a high-fat diet showed an increase in en€rgy intaÌe and eneryy expendituÌe, a decrease in gross elEciency alld no vaÌiation in lipid gain compared with rats led a loFfat diet. so that caÌcass liDid cotrtent was aboui 1 1% in both groups ofrats. Carcass lipid content was also about 11% in hypothymid rats fed a low-fat diet (Table l), indicating lhai, when dietaÌy fat contetrt is low rats are able to avoid excess fat deposition evetr in the absence of thlToid hormones. Or the other hand, when

1 5 0

minutes

after feeding

Figure3-rEF alier low{at and highjat meals measurcd in hypolhyroid rals fed a lowJal (o) or a highlai (.)di€i. (A) TolalTEF time course measured in saline'injecled Ets afier a ow-fai meal. (B) Obligalory TEF llrne course measurcd _{in Prcpanolol_injsted} rats afler a towjar meat. lc) Faculralive tEFtime courss calcLrlated liom the dillerence bervveen totaland obligalorylEFaftera low{at meal. (D) ToralrEF lìme course msasured in saline injecled rals after a hish-faì meal. (E) Obligatory TEF llme course measured in prcprano olinj€ct€d rars afier a high-far meal. (F) Facultative îEF time coursecaculated irom lhe diiference betlveen lotaland obligarory TEF afiera high-fai meal. Values are rcpoded a of iive difiereni rats.

114 s l,sra ad 'rhos EL&ìP8rN JonRNv .F P\Ì..8ÌNoLocY tlqe_) rt6

Figure 4 nlegraled-fEF afler low-fat and high fat meè s inrhypolhyrod rals fed a

owJalora hiqh-fat d er. lorè inteqratèd TEF (saine injecled rals) and oblisalory integraledlEF (propranool injected rars) were calcllaled between 30 and 180 min after mea consumption. Facultalive inlegraled lEF was calcllaled ton lhe dlference belween roìal and obligarory 'fEF.

ValLes are reporred as meansl sÉM of live d lerent rats iP < 0.05 compafed wilh hypothyroìd rals ted a low-iat diel (two way ana ysis ol varia.ce folowed by hdo-lalled srodenls r resl. "P < 0.05 compared wth a low-far meal (lwo-way anaiys s ofvanancè fóllowed by 1woìailed Studenl's t-tesì).

n

E

a

low-lal héa high-t.r heal HYPO-THYROID RATS

F E D I. O W - F A I D E I

low-iar héal high-lat móal HYFOIHYRO]D 3A'IS

FED HiGH-FAT DIE'I

dietary fat content increases. thc \driual absence ol serum lhyroid hormone levels aÍoids the deÍclopmcnt of those adapiive responses tound in euthyroid mts (5, 9, Ì0). thus suggesting that thyroid hormones are important in counteracting exccss fal d€position in response to hish-fat feeding.

\{e have also measured cephalic and processing Tm in hypothyroid rats fed a low lìr1 or a hish-fat diet after a Ìow-fat or a high-fat meal.

As far as cephalic T[f is concerned, we lound a sisniiioant decrease alter a low-fat mcal in hypothyroid rals lèd a high-fatdiei comparedwith those fed a low-lai dict (Iig. 2), but no variaiion aller a hish fat meal (Fig. 2). These results aÌc due to parallel variations ìn ihe propranolol-inhibitable componcnt of cephalic TEF (Fig. 2).It is weÌl knoÍ,n that the cephalic phase oITEF is induced by sensory stimulations, namely tastc. texture and smell ol lhe food insested (15); in agreement with this, we have lbund previously lhat cephalic TE! after a high-fat mcal (which is preferred io a loú'lat meal in a two-choice preference tcst) was higher lhan TEl,'aller _{a low fat meal {Ì0). The present} rcsults show that in hypothyroid rats which are used to the energy-dense dict a lo$'fat m€al elicils a signifi cantly Ìower TEF than a high-fat meal (Fig. 2)i ihis decrease is completeÌy duc to a decrease in ihe làcullalive component of TEF (Fig. 2). This result suggests that pre\dous lèeding experience can affect facultati\rc cephalic TEF: rats familiar wilh a more palatable food aÌe Ìess responsi\rc to a l€ss palatabl€ lbod. W < h d \ e nl.o l']er.ured r h e p o . r p r a , î d i a ì ' n . r . a . e i.ì RMR aller a ìareer meal (Jskl) (Fis. 3). our results shoÍ' that ihere is no varialion in processing TEF afier lor'-fat and high-fat meals in hypothyroid rats led a high-fat dict compared Í?iih ihose fed a low làl diel

(Fig. !t). Some differences, how€vea become ev,oenr when the iwo components of Tm aÌe examined: obligatory TEF and lhcultative TEF (Fig. 4).

As far as obligatory TEF is concerned, a sisniîcant decrease in TEF r'r'as found in hypolhyroid rais lèd a high lat diet compared with those f€d a low fat diet, alter low fat and hisb fat meals (Fls. 4). This decrease can bc due to the làct thalchronic teeding with high fat diets inhibits dd nd,o lipogenesis (19, 20). Therefore, in hypothyroid rats fed a high-fai diet, storage of Iàt may occur djrectLr irom dietary lipids, with a lo$'er energy cost than lhat associdted with storage of lipids via d€ noyo lipogencsis, Ìr'hich mainly occurc when mts aÌe ted a lor'r'fat diet (Ì8). Thc lower oìrligalory TEF lound in hypothyroid rats ied a high-fat diet is in agreement 1Ìith the increase in both fat gain and gross efficiency lound after enefgy balance measurements lTablc l). In addition, a d€crease in obligatory 'lTF after a high-fat meal comparcd with TEF after a hw tat meal was lbund in troth groups of rats (fig. 4). This resull can be explained by tahins into account thc fact that obligatory TEP is innuenced by the amount and naturc of lhe nutrient consumed (15)ì since the fraction of erersy dissipated during digestion, absorplion and storage of nutdents ranges from 5 io l0% lòr carbohydrate and from 3 to 5% for lat (21), a high fht di€t, \'rrhich has a higher fat and a lower carbohydÌate content, is associated !Ìith a ìower cost ol lurlexl assimilation.

As Iàr as facultative TEF is concern€d, a significanl increase was lbund in hypothlroid mts fcd a high-fat diet after lo\'\Llàt dnd high iàt neals (Fig. 4). Thls rcsult can be cxplain€d by taking into account the fact that brown adipose tissuc (BAT) has been involved in the processing TEF (Ì4. 22) and high lal diels stimulate

ùnoPDAN JoriRNd 0f rNl).cRrNoLocY oee 7) r 36

BAT activiiy (18). In addition, it has been shown that BAT shows some characteristics of its recruìted state in hypothlroid mts (23 25). Therefore, ihe increased facultative TEF in hyporhyroid rats lèd a high-fat diet . o u l d o< Jue,o aî inJrea$o B A I t h e r m o g . n e s i .

In concllrsion, our results indicaie that hypothvroid rats are unable to develop those adaptive mechanisms which are usetùl to counteract obesity In fact. the lach o Í l J r n h i b i r . b o r h a c u r c d n d c l ù o r i . r h e r m o B e n i , responses lbúnd in euthyroid rats ied a high-fat diet

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