METABOLIC EFFECTS OF HYPOTHALAMIC HYPERPHAGIA

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  • tk pre-eating interval, but mnven3ely the postprandial satiety in t end is highly CORC- bed with the meel sire. Many of the p m posed mechanisnls of foul intake regulation 8ttemPt to explain the repletion of depleted body en-. Perhap such mechanisms are not furtiming in the regulntion of meal in- take, but are dlective only in -regard to boger-tenn regulation.

    The mta appeared to be eating to main- tain an exce~18 in the body energy level, and therefore would not eat win after a meal until surh an energy load lost. What tbey

    ate in this aerond meal was unrelated t.p the pm-ioua time interval.

    11sffnen and Tallon have, in an excellent experinlent, &own that daily food intake and number of nreals are well regulated and remain relatively constant in rats. But them ie much variation in meal size and intmyda between meals. The most striking - d t vai rhe finaing that the quantity of food eaten during a meal is not d a t e d to the intend since the previous nleal, but, instead, the pastprandial i n t end is correhted with the mtal sire.

    SevetaI spcck of laboratory rmimah h v e heen shown to become obese following &om in the ventromedid nuclei of the hypothahnus. The CBUR of thm obesity ha.. not alwaye h e n c-kar. 3fmt wn.0rkt-m have that, in pan at Icast, hyper- phqia is responsible. I t has been suuglpltec! that physical sctivity oc thyroid function may he nduced. G. Stdl6 (mz N u t d i a R w k ~ 24.93 (I=)) haw & o m that there uc w)me definite cadoc-rine gland changes amompaaying hypothalamic obeeity. P. W. Ban el al. (are Nutt ick &&to8 24, lbt (fRM)) have found that hypothalamic oaknity of weanling rats is muwiated with growth impairnwnt. Apparently, variwb metabolic regulators end kliavior patterns are altered by leciiom in thc ventromcdial nuclei. K. K. hlay and J. It. Beaton (Catlad. J .

    . P h y d . Phannord. 44. 64f (fsli6)) have st iidied hypothalamic hyjwrphagia in adult mtr. Food intake, weight c-hanp., growth, mcatnholic mte, and certain mbtah)lic char- rteristics of thew rats h a w been compand with t . ~ ~ ~ ~ ~ p o t d i i ~ p ; c*hturrctcriatic-r o f normal rats. The ~ u v a m c t c r u w ~ m c-onipnd for the

    two phases of hppotlialamic hjyerphaeia. During the dynamic phase there is very rapid weight increase, m-hilc duriug a later static phae, weifit iacrpasesmuch more

    Adult male rats were fed ad libitum a q n - tbtt ic, hi& carbohydrate, diet. To caute by- pcrphrqgin, electrolytic l&om were p r o d 4 in the ventmnwdial nuclei d the hypothala- mum.

    Fwl intnke was memured between the seventh and thirtieth, the eightpsixth d opc hundred acK1 third postoperative days; t h two pwiais coiD,cide with the two p w t h pham of hypnthalmic hyprphrrfia: dynaniic and static. F d intake was du, rneammd iu an unoyerated group. T h e averqw fuod intake of the hypes-

    phagicrr W.R higher than that of the controls during bnth periods (27 f 1-50 vems 18 f OX) g. per rat p r &y, and 26 f I .50 v m u s 17 f 0.99 g. per rat per day, rPspecti\-t-ly, with I < 0.001 in each caee). Sixty days after operation, the averap body weigbb were about 525 vcmue u)o g. for the hyper- phngiw and controls, nrsptmely.

    FWween the tenth and wventcentli poet-.

    SlOWly.

  • operative days, the rats were placed in a re- volvingdnm activity eage attached to a shtionuy living eanipartment. This WM re- peaed h e e n days 112 and 116. The IIDT- lnalcindlan . activity pattern d the hyper- phaghraodmilnrtothtdtbsinfret con- t r d ~ - goup -em much more active d w tbe wt than dwing tbe b y . A ~ v - d tbe blrperphdc rrts d e tk dy-

    JW& plume ~ ~ 8 8 signi6eant.l~ greater than tb.tdthccootmh(P < 0.05). Mag oxygen cormuxnption wm me!&-

    wed for mta deprived d food for four hours. Thehyperph.g icrats~tested21d95 days after operation when their b@y weights Wem 299 srd 495 6 rseptctively. control rateren tested twicedso; theyweighed 282 and 440 g. respectively. With these rather d differenmu .irr rpdgbt. indicating only mild hyperpbagia in this group of rats, no ditiereDoee mye found in o x y v consump- tion.

    Thymidd uptake d radioartive iodine (Im) MI measured in the hyperphagic and control goups. 16 in the pmvious experi- ment~, t&e byperphagias were taeted during both char&umt * ic phsess. The rata were fed a diet without iodine far two rre$ts prior to the tcsL day. During the dynnmic Phrse, tbere was a~ insignificant trerrd for the hy-

    v p e r p h e having a loser Im uptake. Dur- ing tbe &atic phaae P uptake in the hyper- ph* graup we8 eignificrntly loner (95 vemm 22.4 pr cent, P < 0.02). and the sub- sequept r8& of r e k of I" wm Eimikrly r e d d

    1- 'on d P-sulfate into co~tal a d a g e w m de te rmid in order to tmt for Chaqp in god acannpmying ex&ve bodJrFei&t gain. Control 4 hyperphagic rats in the dynamic phase were studied. Twenty-four hounr following injktion of 10 F. of Sbul fate into each rat, they were srcrifraed. Incorpcmtion of W' info ecletal cartilage m-ms found to be normal in the dy- namic phsa of hypothalamic hyperphagia. Thk k evidence that the h ion does uot cause an dect on deletat growth.

    Incorporation of acetate-1-04 into adipase timue d r e b d free fatty =ids in vitm w m determined in rata of th control anel

    poupa "hem WM a strong trend toward iawrporstion d rrcStrts1-C" by

    diparc tissUt of hrpcrphsgic rats d u r i 4

    hypeqh& (both ststic .bd dynrmic)

    both phsgiq tipol* and rrleasc d fme fatty acids were r e d u d . The determination of incorpwation d glu-

    coec-U-0' into lipids indicated a tmd to- w d llip inc& rate during both ph- of hypcrphagia. Oxidation of g l u c m to PU- bon dioxide m'o not .tfecttd during ather

    A I M er.udies that have dedt with growth characteriRticR of the hypothalamic hypw- phagic animal have been done in cither the dynamic or static ph- A l m d norre has worked with a n i d fmm both w, nor have tbey mezIlrund such a variety of puam- c f ~ a The work d May a d Beston clearly indicates that 0bServ.tions made duriw one p b are not necesssrily applicabk to tbe Other.

    It is not clear why the autharu sek- la l for use mde rata rather than fcaules. The female rat hm been more extensively studisd and hr pew better adapted to this type of study, since it reaches a maximum weight and then ~lrarps very little. Male rata continue to gmr much b w and becobDc mueb b i w . May and Beston's work indiutts that

    during the dynamie phme d hypothalamic hyperphagia them is nwmd thyroid func- tion, but that during the static ph&p some degree of thyroid hypofunction may exist. Unfortunately, this wna kt borne out by the resting oxygen mmumption toRtcr. It is pointed out, though, that the mta tmtcd for oxygen co&umption were the least hyper- phagic group studied. The hypcrphagic rats haw pwiously

    been shown not to change their nitqwn deg mitioa appmiably, but d y to develop larger fat depotw (D. C. hlontemum and J. A. F. Stevenwn, Am. J . Phpiol. 196.76f

    Duriw both phrura, d h w -

    fie=..

  • (Im)). May and Beaton did not meamre body ,protein content of the rata as a measure of growth, but, rather, tested for 8" i k r p o . ration in c0St.l carti&. Incorporation of 'EU per millipam tierrue catta cartiIage WM down to be normal during the dynamic

    This probably i n d i c m that ukeletd growth W ~ E J not deer by the hypotha- lunic lesion, but also that it was not in- creased appreciably during urcee$ve food intake. Other work on young male rats in- dicsted that p w t h can be decreased by hiorrs in the v e n t d i d nuclei d the hypothalamus, although obeaity d t a (m

    It h d been previously suggestsd that N t d d h b k t ' 8 24,168 (1m)).

    depot fat was mobilized more slowly in hy- p o t h b i c hyperphngica than in amtrob (H. Mankin d d., E- m. 4 4 (1860)). May and Beaton'a work u s i 4 acetate-14" and glucokU-C" -b that there b increaaed synthd and depod- tion apd d d lipolpsis of fa& As haa been previouay shown, obadty n-

    sultinq from hypotblamic hypeqhagia dur- the dynamic phamis a&t of aa ipsuffi-

    cient increme in 6pont.rrews activity to

    During the dynamic pbe, there 51 m evidence of altered thyroid function or dteb . td growth, but there b i n m a d li- d decreamd lipdysis. During the atatk phme, thymid hypofunction may a h OCCUT

    compensate for the incrersed - hf l . CORRELATIONS BETWEEN DIETABY FATIT ACIDS IIVEP .

    FA'ITY ACIDS IN TEE RAT

    The effecta of controlled intakes of essen- tial fatty acid9 (linoleate and d d o n s k ) on the composition of various tissuc lipids have been quite thoroughly invedgatd by R T. Holmsn and hL co-worker8 (Holman, Fd. Proc. 23, 106g (UW~)). In these em- perinienta, the esscmtid fatty acids were the only source of dietaw fat, m that changea observed in tisue lipida repreeenced the re- sponse d~ essential fatty acids alone, uncom- plicated by the effects of other diet- fatty ride. As intake of fatty acids of the lino- hate eeries ineread, tisque lev& of *this series i n c r e d , as would be expected. Also, h u e levels of fatty &ids of the oleate and palmitalcate series decreaeed m the intake of linolcate or arachitionate i n c r e d . . W. 0. Caster, H. 3fohrhauer, and Holman

    (J . Nultilbn 89, t17 (fseS)) undertook to test whether changes in the fatty arid com- position of liver tissues obaervcd when a

    single ementid fatty acid waa fed w d dso apply when an eaeentid fatty acid WWJ fed -her with other fatty ecids which am major components of the n s t d y bccur- ring fats and oik 'henty+me fatty acid mixtures were prcpred from xlatuml fw and oils, with the addition 05 puri6ed fatty wid esters aa ae(eded to obtain the dcsirpd compoeitioll The xnixtum were &signed (1) to have each fatty acid at eeveml levels in the variouff diets, and (2) to reduce the degree of codation which existed between certain fatty acids in the ~ t ~ r r l oila Calcu- lation of the various lipid mixtures nma done with a digital cumputer.

    The major fatty rids in the mixtures were myrbtate (14:0), palmitic (16:1w7), stearic (IS:O), oleic (18:ld), Linoleic (lS:2w6), and lindenic (18:W). Tbe num- ber after the *W' gives the location of tbe 6rst double bond in the carbon chain if the

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