Document qkEaLLex9RgdBOmqgVG2DBqZM

Sex Difference in the Number of Adipose Cells from Genetically Obese Rats It It mH known that ihwk k no Incnau In tin number of adlpou colli In many piljndn of operlmental obblty. In ganwlcalty dm* mb*, otjobobaa* hypwtlycaemk:' 1 or ytJkm obau* lyndromee a, well u'ln hypothalamic okotIUor produced by aurobloglueou In min* or elaraotaelc l--lnnr In roll'. Dim* It only an anferpeheM of tht edipoae calk. The taino ntolto an obtain** In u made obata by a high fat 4bt*. Titan b only one knolnf tMapilen to Ikla rain: obaally Moot* by a high fat diet Itj female mice', In which Hit number of ceth k inctueed by * fetor of 2.5. Beeauee male anlmab wen uni In all aapertmanti except thy but, Die quotllon arket whether then may be a tee difference In the edlpoee tkeue development In obeee anlmab. OenelicaRy obeee rate (fare)* 2-5 monthe oM and their llller mate*. M with thy control diet, wen ueod. Whole perlpenllal bl padt web (weighed and treetod at pnvioualy dttorlbad': portkxu of htMdoglcel tectioni on tUdet, proJeclod, on the (round (lab of a Frofecllna mieroeonpe, wen oountad for their adlpow oyllt at a magnification of x 130. The mean volume wat calcultud and the number of adlpoee oelb tetimaled by Iht ratio ttf hi pad weight to mean adlpoee cell vohmw >0.11 (0.91 b IMmeatumd deneliy of the pada). Tebfc I thowt that Ike body welghu of obeee ntt doubled In the bmalee but Increkaed leu In u.e make. The weiaht of eerlgeniul hi padt IncMaad 5.2 end O.T-foM In irtaka and bmalu napectlvely. Adlpoee calk anlarpad 4.( and 4.0feld In obeu make ant) bmalu napcctivaly. In mtb obau mla ban wan lignlfloaiuly bwer apldidymal adlpou ealb than In thair Uuet melee! but a 2.5-foM Incraau b Mr number wua oburvad In the panuhatrlal% of lha obau bmalu. Tabu 1 Wafer* *1 the torn and el eh* Two fwfeennot Pat Pab at t.l Month Old OonoMeoBf Mo and Pernor nue end The* Molt* Body wel|ht (|> Loan Utter inetea 274116.0 4) 2.1210.260 W> 276 1 25.5 rs) 5.M 10.451 Obeee 266117.3 P.0P* 0.327 1.2753.2 6.50 0236 Exception# lo Ihe rule that only hypertrophyto obunw^L mak adult anlmak had bean claimed: them k hyperpfeele of adlpoee eelh in nb eAer repealed infectlone of Ineubn*- or meal bade". In Iheee enlmek ban wee no btenatt bl be weight of the epidldymel hi pad, end ndlpooo cad volume Beamed to be reduced: be difference#, however, wen very email. The principal effect. In be two ooeot, wu greet Increaw in be total DNA content of be peb (4 X% be meal fed rate" end +100% fo rale treated wlb maulin'*), guch dlfferaneu cannot be be effect of a marked kyperpbafe: be weight of hi peb wu unchenped and cad vohima vary eUphdy metier: to II etui he concluded that than wu an Inrriaeid DNA eonuni In etromal etructune. guch an affect her keen etuUbhed la hypophyeactomlud nb after Injection. of aomatoirophic hotmont: be nu of DNA tyntheeit of eupporting and vucular etructuru wu enhanced, bul then wu no effect on dtvtelon In adlpoee cab11, la my rate, the hietdoglcaf appunurce of pertgmlttl adlpou Ibeue wu be ume u bat dneribed for rab made obau by a high ht diet*. There wu no difference, except for the tiu of tha ode, batwaan bl tiuuro of control and obeu rau, ehheuidi ben wu o marked and etmilar hyperinruliniem io mabe u In bmalu m be obeu (roup (to be publbhed bbr). I bank A. Abide for technical auklonee. Dam Laboratory af Btatafy ami Htattatt Na/rtMaa, CHAM 2P2 Km Mw kfarrkr, TJ Kart, I Received December 15.1*10. iDmen. I., Tgjhdel, I-*., end Wutmen. i., Acta Marptaat. Nrrrt.Scamt.~l/ttl (IMl). ---------- D,, Wlnand, I., PUmelb. >.. tad ChrUlefOe. I. (inibepnu). * Helbnao, g.. Thebnder, L., Tlthdel, I-*, Acta Amt.. 99, bO (1945). * Heilman, Tlthdel, !.. . >., MM. tap . *. 402 (IM2). Hindi, I.. end HU. P. W.. / Uatat Hat . IR 7T (IP*). * Umoonbr, D., Arm. dear. TSkraar. Marakal. Earn.. 99, I (1970). T ' Umonnbr, D , Eaprrlenttai, litlt (1970). Dicker, L M., aod DickeUr,. ti F, l. Hated., 92, 275 (IWIk * Heuebergo, P. X., end Heliuebefpr, 1. C,, Aamtitt.. 117,199 (1957k ;1*1 Kaadova, L., aend Vrmenne. A.. Harm. WMawtmakb. AHant..,. I2., I11ll (1970). " grain. T.,Kudova.L.. Fabry. F,, Updo. Z., enti ibo vT-WrlUatom, 17, |}5 (1961). " Hotbobcrp, C. H., and Veat, A., 1. dm. bma.. 47,2419 (1941). k .W. Body oiffhi <*> No, of odlpooc cefh (in ` 16312.4 g) I.64t0.tif pm*) 179244.4 i*) 4.00i 0.262 320 13,6 I9.fr 0.71 ly53643J 6.44 0.460 Tbl caO volume of Ilk ibau group* feeruaad, bul ca oumber htuefed ebb bjjbe ferkak enup 6.5 Hum), A1 dHTumcu ere jUfegydrBum (F4MI1 Valuee era meen gee. There wen in enlmeb Hi eech of the few mupe. Hypertrophy of the adlpou oalb io tlw obeu bmalu could only aoooual foe o paUnetrinl ht pad weight or f.4xd.0 6.64 g--9,2* g leu than the actual weight. And to about 10% oObe wdlpit of (he path wu duo to formation od new bl oolh whla wan bemeelvu hypertrophied. i cbqrty feeMMkhed e eea difference in tbe r parlKiHat adlpoee Oene. They ob In pood I with bo flereturo whkh recorde no Incteou hi ht aiber in mob pbeeonk or mbd1"*. Mlbomwaeo I bgbarplaeb In be paramebtlal ndlpooo oalb far bo bmofet which wu very1 thnlUr to Ihoct chewed In femak ndoo made obeu by a high bl Ufet\ Polychlorinated Biphenyl absorbed from Sediments by Fiddler Crabs and Pink Shrimp PoiYCHU)ftiNAt*D biphanyW (PCBs) mbmificturcd in Um United Sums, Europe; end )tp*a nd need as pMetidaafi, Bum reUfdaAU, irmiUitini aod Bait eachania IMdi and in many other products'. Structural rattled to DOT. soluble in lipM bul relatively Insoluble Io water, and extremely persis tent In the environment1, they have been reported In many marine and estuarine organisms1. One KS, `Arodor 1254' (Monsanto), was reported in water, sediments, and biota from Escambia Bay. Florida4. Id August 1969, pink, while and brown shrimps (ftearur dWranew, F. Mttftnu, and F. aifeeur) from Escambia Bay were found to contain whole body residues of `Arodor 1254' at concentrations as high as 14.0 p.pjn. Most was poneen trated in the hepatopanaeas; residue* In seven compoeile sampiee of at host ftm shrimp* ranged from 0!6 to 120.0 sp at la April 1970, flddhr orabe (Ucm mlmx) oofleded at Ifcsee stationa along (ha tower Bacnmbia Rher and upper EacamMa Bay had Individual whola br-tw raeiduaa of 0.45 to 1.5 p.p.m. MONS 083990 NATUhC VOl. 231 MATj T 1071 To'datormlna the ^bjribullon of `Aroctor 1234* In the eeluery, forty temple. if waur wcra collecied In *lau bolllH; twenty IMNimnU wan dofkrted with a cow or dredp. aampfa, and mony Muorine oMnlm were cnpturad by irawl and dredpr 13nm were attained by a liquid chromeiotraphy*. The laryeal MrtimuUimo of `Arador* men found in the eedlmmla. In one eiivfy (February 1*70), eoneenlraiione rented from 0.4 to (1.0 p.p.m. In a eampW laker at the die- dare* point of the Induelrial plant that eeeldenlally nieaead the ehtmicel and at eleven elatlone aatandini Id km down- (Fif. I). 'Arcelor* wat n bed above the pUft.bul eolt eampiaa hum the bank near touth of the fiver AJ km downetraam IVom tha eourea had 1.7 p.p.m. of Ihle'chemical. Subeequent tamphnoe hoot e In lha.lay fhowod Hide chanta la tha amouMe of _ ______I oven afteroloe moatha. We Ibanfon ianetl- naiad whether rhrWefid Mdler crnha oouM aaeumulate TUodoc 1154' ffoae the rooimcnu. ' 1 upper end of five aquaria inclined 10 degrees so ai to simulate a natural environment. Ten crabs from population which had no contamination were placed in each aquarium with ont serving a a oontrol. Water with an average aaliniiy of 27 p.p.t. at 13* C flowed et 3 l./b through the lower end. Both ituimp and crabe were fed Aih containing <0.03 p.pjn. 'Arodor 1254' each day for 30 days. Five craba were removed from each gquarium, killed and. rineed with a 30% mixture of acetone and water to 'Amove 'Arodor 1234* from material adhering to tha eaoekeleton. To eneure enough riemt for analyeea, individual crabe and pooled eamplae of hepotopancreas from shrimp ware mixed with anhydrous NaflO and extracted with petroleum ether in a foahlat apparatus; the extract was purified with 'FlorMI'*. 'Arodor 1234* was quantitated by gas liquid chromatography4. Tha ratio of individual 'Arodor* homers maintained integrity in tha sediments and tissues of test animals throudtout the investi gation. TeMe 1 `Aroeter 1294' in IndMdual fiddler Crete end tttpionanerase tram hnh Shrimp Sediment Sandy silt* smt Sendyim* mi Sandy till* Siht gtttt Send control* Silt control T 'Afodor 1234* Average end 'Arodor 1234* In In sediment range or *Arodor combined hap- (ppm-fry 1234* in Ivo aSopanerees from wddit) IndividualflMhr iSurormen embe (p.p.m. thrimp <p.pm wet waiiht) wet wiqH) 41.0 30.0 3.7 4.0 4.1 2.S 1.4 ND ND HOi 23.0 176>.0 -- 3.409 -- 3.2 0.9 -- 0.30J 2406 01 9.1 1.3 07 u 0.2 <02 <0.2 The esmplee ofcreb end shrimp were kept for 30 dags on aetere% : occurring tedmente eonteMna 'Arodor*. MortaWse secunoi In some groups of thrimp which eouW not be attributed le `Arw dor 1234. * Sediment which contained panicle* oftend > 394 pmIn diemeter. t Sedbnmt which contained parikhe of aand 334 pm or tea*. --, No temple. ND, Not detectable. anoa^ttM , I\ \ lowtr Eacembli Mvtr, upper _______ it doSeard on rtm. iS.Im_____ of `Aroctor 123k* Mrt M web notion b |lw par* par mHliori (p.p.m.). ND. Hoi low comamlnaiad Imonu (Table I) wot* oolloctod with EeaerSaVlverT 6rp(he uopfp'0r.r( fltocamb.ip bBeqeychoqudndlowanedr oMHMul eempUe of -- fro-m -the eonumlMMd Mrtlon the rtve# Mrvrd or uMonUunlntM OOMfOlC. IFour kllotrehu of oOok fhk rhrlnp (F. r on) from o population wiucn noa prev_k_iu_c_t_y_i_bown no c Milan wNh 'Arodor* worn pieced U mok ctinhw Murtia' todtijl ir C Bowk* rt t mu of 12 tR nM onoiWMc QHy< df 27 port* nr Ihouwnd (P4M.), covered the Nfaetnitum to o deprh df 10 cm. ' fibre embe (l/.THirtor) wwe -cored "tglpiK * pUc| Mm on jvc MdUni cubrtroNi coBraH^pUnbad. Fw ilk>rtm of aochof the rcdlmeotr wen pUred Is Hw Fiddler ertbe and rbrimp oxpocod lo the coolamioalcd redinwnta oocumulilad 'Arodor 1234* In thdf lirouM by InfMling oonlomlnoled redimenl portldM or by obtorWot Ibo leached chemical from wtur. They rlflad tht aodimanlo before inpMlint the portldM. In mod carta, tin amount of 'Arodor* in Individual crib, or in rbrimp bopoioponcmoc woe directly routed lo the amount In the ledlmanti. Wo analyMd the dl.trlbullon of lha chemical In the aodlmoni In rdtilon lo portido ciao ind found II war evenly dMrlbuud. Larpr eonoonlretioni of `Arodor* rwldum moy oko aocumuUio In lha hepalepancnat of thrlmp eapoood to randy illu bacouM ibo chemical bachm from Uu todimanu and b tfecorbod throuph the pile. Three and a half porta per MMIon (p.p.b.) worn In ibo effluent wour bom the aquarium with randy dlt (41.0 p.p.m 'Arodor*); the water bom the rUt (10.0 p.p.m.) had only 0.3 p.p.b. Ew Ihouyh tiddler crabe won not oominuourtr cowed with want, lhay could ham ofeulnod 'Arodor* bom the water aa thay wotted thdr tffla. Wo bom dwnonalratad mpartmaotatty dial 'Arodor 1234* con entor the -marine food chain bom mdlmndt Othtra* bowl4WMjhbclamlca(U Mdwr Bophk HU ruch m Mi. and linoo FCBa ora wldaapread In lha world1, wo rhould MOMS 0 8 3 9 9 1 beaxfcc mon gbrt to the mmdm, raovemeri gnd dlteu of 0MM ehemleele In the <nvirement. . VS Kmtraamental IVmkMm Sgancr. 0*ff Mrtrat Lafiarafarjr, I ftPANKArMtlHfl | D. R. Nimmo P. D. WHJON R. R. Blmxmam A. I. WOJON, IUN. Received fcgumber 17; r i Dtombtr 10, 1970. lynoMs, L. M.t M. &tjr.\ Cmtn\, mi Tfcurfoaf., 4,121 (1969). * \ R. W., aid Brains, V., Emkmmmt, li. 16 0970), j, 0. W., Rtaeh?f ffbeatkias>hT. D~. R~ . H**erman] -I. 0a., and* , m. m ^W` feSTTit* __ viHranl, v> nmwrw, Duke, T. W,, Uwi, i. I., Gntfwfi. mi VfMkrnt., t :\mk, A. O.. Obson, M* M Jim.! A. I., Jeff. Awbm It, A., /. 00k. We propose the trivial name, 4-ipomeanol, for thii compound which I* e dihydro derivative of Ipomeenlne, l-0'furyl)-l,4pantanedlone, another known metabolite of aweet potatoes*. There are no reports Indicating toaWty for ipomeanine. The empirical formula of 4-ipomaanot, CtHiaO (molecular weight 164), wee deduced from the meat spectrum by Mad matt measurement of the f-H,0 kxi. (We msaiured a value of IS0.070i 0.002i CH|fOi requires a value of i90.061.) The p-fUr>lketo moiety waa Indicated by lha characteristic nuclear magnetic resonance (NMR) signals for the fury! protons9, by the stretching frequency of die oonjuptod carbonyl group, by the uhraviotet spectrum* and by the Intense mf* OS km (frC*H|0-C0*4)*. * *T*he third oxygen mdies Is a hydroxyl group (v J.J90 cnr1). Double Irradiation NMR showed that the hydroxyl group waa embodied in a methyl eerbinol. ITw chemical ihifre of the remaining two methylene groups wave consistent with the unhyantbed form of dm structure. A Lung Oedei 'actor from Mouldy Sweet Potatoes moea batatas) W havo already daacrlM the toxic propertice of eweet potato tuber. infected wjth common moukU1 ,l., The toxic property, are not dinctly Attributable to the fungi beoauae polaona were not found Men the orpaniuna were grown in autoclaved tweet potato Murry. The experimental Infection of viable iwaet potato tHopa or of the intact tubera neverthehat reaulted in the production of many ftiranoterpenoid com pound., mm of which am markedly toxic for laboratory and oommardat anlmah. Aa well aa the previously recogniied hepatotoxlna ipomeatltarone K + Vngetone]* Mi Ipomeamaronol*, we have alio ieoiated a more potant toxin called lung oedema factor (LO) from ethar and chloroform aatracta of both artificially and naturally contaminated auRat poti-toea1, which tecall. that natural oulbreaka of mouldy iwaet potato potaonlng In cattle all deaerfbe raapiratory dulmac related to lung oedema aa the principal algn of dlaeaae*'f. | On tne other hand, hepatotoxldty which might be attributable to Ipomeamarone or Ipomeamaronoi haa not been reported in moat enrootice. Pmh tuber alieea inoculated with aweet potato alurry-ehaka ouliuraa of fttaerfem/awnMm and Incubated for approximately i daya at 22a-24* C contained aignlflcant quantltlea of all three toxlm. We panlally purged theae metabolite, by partitioning crude ether aatracta of mfreted iwaet potatoca on allien pel column. ualng ahitlon with n hexeneohyl acetate gradienL The eolumn aluatea ware monitored by Ihln-leyer chromato graphy (TLCl (tlllca pel; *; I benaene-melhanol). Ehrllch'i nagant produced twelve fifteen coloured apota rapreaentina flirtnoterpenoid. on TLjC atrlpa developed from the crude eTher extract. Preliminary toxlplty eaaya In mica .bowed Rial lha LO factor waa auodeteJ with a raddhh-purpie epol hi 0.4 which contained numerous compound, by gaa cflromatogr.pt,lc analyaia. 1 Column eluale enriched with LO, eonaiatlng chiefly of the nddiafl-purpta TLC apot malnial, wna putiflad further by preparative gaa-liquid chromatography (OC) of trimathyltllgated (TMS) product. A aingle OC peck comcponding to the TMI after ,of hmg tonic makrial wna obtained. Wa ranoved thjBVS group'by add (tpqflrolyalg to give pun tonln, n eotourlSFofl with c, pungent odour. SpMral avidanm (Table I) Mioilet that lie atructure la K)'-fbo04-hydntxy-)- aanlanoaa. I Table 1 Ipsctfs et 4-tpewseael Infrared. Ultraviolrf em~' (neet) M|qi^ NMK.9p.pm {6cm MS.*/#(*> 9,490 (OH) 249 (*9,000) 9,110 (fUryt) 211(19,100) 2.040 2.900 1,675 (coni. OO) 1.560 (niryl) l,SW(furyl) 1,160 M0(fury0 1.15 OH. d. J*6Hx,loi.) M] m 2.90 (IH, breads, OH) t, I7Hig Itt (5) Mot sculer ion 199 O) M-Ot, 159 (6) M-HgO 9.79 (IH, m, .n(iiL md'-CH) 7.42 (JH, a, J'-CH) 9.07 (IH, as, 2'*CH) 110(47) OH fUryt-<b- CH, 09(100) furyhCO 4-Ipomeanol is acutely toxic to mice, producing the hmg oedema and pleural effusion previously observed with crude sweet potato extracts. Doses of toxin (1-4 mg) given intreperfioneally to mice produoed immediate signs of general Illness, followed quickly by dyspnoea which gradually inenaeed in severity to the lime of death, apparently from anoxia, in 9 to 8 h. Comparable quantities given orally were usually followed by a short period of apparent latency (2 to ) h) followed by increasing respiratory distress leading to death within 24 h. At post-mortem examinations, dear fluid, eometimea aa much as 1 ml. or more, dripped from the ooetrik whan the animal carcass was held with He head downwards, The Imp were frequently congested and surrounded by 1~2 ml. of deer pleural fluid. Microscopic sections of Che luttp stained with heematoxylin and eoein showed Intrwelveolar oedema and congested blood vessels. In some animals these was a slight increase in abdominal fluid but we observed no significant pathological changes in abdominal vleeen. V Wa have also Isolated an bonier of 4-ipomeanoi, tentatively asdgnad the structure 9^3'-friryf).54iydroxy-2-pentanona, which Is under Investigation. Sweet potatoes offered for sab in food store* often contain ipomeamarone, ipomeamaronol and 4-ipomsanol1. The exact MOMS 0 8 3 9 9 2