Stunting and future risk of obesity:
principal physiological mechanisms
Baixa e statura nutric io nal e risc o d e o b e sid ad e
futura: p rinc ip ais me c anismo s fisio ló g ic o s
1 Discip lin a d e
N eu rofisiologia e Fisiologia En d ócrin a , D ep a rt a m en t o d e Fisiologia , U n iv ersid a d e Fed era l d e Sã o Pa u lo. Ru a Bot u ca t u 862, Sã o Pa u lo, SP 04023- 060, Bra sil. a n a fisi@ecb .ep m .b r 2 Hu m an N u trition Research Cen t er on Agi n g a t Tu ft s U n iv ersit y. 711 W a sh in gt on St reet , Bost on , M A 02111- 1524, U .S.A. su sa n .rob ert s@t u ft s.ed u An a Lyd ia Sa w a ya 1 Su sa n Rob ert s 2
Abstract Th ere is a fa ir a m ou n t of ep id em iologica l ev id en ce sh ow in g t h a t n u t rit ion a l st u n t in g ca u ses in crea sed risk s of ob esit y. Ob esit y is in crea sin g d ra m a t ica lly n ot on ly in d ev elop ed cou n t ries b u t a lso in d ev elop in g cou n t ries, su ch a s Bra z il, esp ecia lly a m on g t h e p oorer. Th e m ere co -ex ist en ce of u n d ern u t rit ion a n d ob esit y a m on g p oor p eop le h a s a grea t im p a ct , a s t h e b u rd en in t h e socia l, econ om ic, a n d h ea lt h ca re syst em s is rem a rk a b le. In a d d it ion , a n in crea sin g n u m b er of st u d ies h a v e sh ow n t h a t n u t rit ion a l st u n t in g ca u ses a series of im p ort a n t lon g- la st in g ch a n ges su ch a s low er en ergy ex p en d it u re, h igh er su scep t ib ilit y t o t h e effect s of h igh - fa t d iet s, low er fa t o x i d a t i o n , a n d i m p a i red regu la t i o n o f f o o d i n t a k e. T h ese f i n d i n gs su ggest t h a t a b ro a d er a n d m ore d et a iled u n d erst a n d in g of t h e lon g- la st in g effect s of ea rly u n d ern u t rit ion , d irect ca u se of n u t rit ion a l st u n t in g, is n eed ed . W it h in t h is con t ex t , w e p resen t d a t a of som e p h ysiologica l m ech -a n ism s t h -a t su b st -a n t i-a t e t h e -a ssoci-a t ion b et w een p rev iou s u n d ern u t rit ion -a n d fu t u re ob esit y. Key words N u t rit ion a l St a t u s; Ob esit y; N u t rit ion Disord ers; Food In t a k e
Resumo Ex ist e u m a q u a n t id a d e sign ifica t iv a d e ev id ên cia s ep id em iológica s m ost ra n d o q u e a b a ix a est a t u ra n u t ricion a l a u m en t a o risco d e ob esid a d e fu t u ra . A ob esid a d e v em a u m en t a n d o d ra m a t ica m en t e, n ã o a p en a s n os p a íses d esen v olv id os, m a s t a m b ém n os p a íses em d esen v olv i -m en t o, co-m o o Bra sil, esp ecia l-m en t e en t re in d iv íd u os -m a is p ob res. A -m era coex ist ên cia d e d es-n u t riçã o e ob esid a d e es-n a p op u la çã o p ob re t em u m gra es-n d e im p a ct o, gera es-n d o ees-n orm e sob reca rga p a ra o sist em a d e sa ú d e e a est ru t u ra sócio- econ ôm ica . Além d isso, u m n ú m ero ca d a v ez m a ior d e est u d os t em m ost ra d o q u e a b a ix a est a t u ra n u t ricion a l ca u sa u m a série d e m u d a n ça s a lon go p ra z o, com o m en or ga st o en ergét ico, m a ior su scep t ib ilid a d e a os efeit os d e d iet a s com a lt o t eor d e go rd u ra s, m en o r o x i d a çã o d e go rd u ra s e p rej u í z o n a regu l a çã o d a i n gest ã o a l i m en t a r. Esses a ch a d os su gerem a n ecessid a d e d e u m en t en d im en t o m a is a m p lo e d et a lh a d o d os efeit os t a rd ios d a d esn u t riçã o n o in ício d a v id a , ca u sa d iret a d a b a ix a est a t u ra p a ra a id a d e. Den t ro d esse con t ex t o, a p resen t a m os a lgu n s d a d os rela cion a d os a os m eca n ism os fisiológicos su b ja cen t es à a sso -cia çã o en t re d esn u t riçã o e ob esid a d e fu t u ra .
Background
In d e ve lo p in g co u n t rie s b o t h h igh m o rt a lit y am on g ch ild ren u n d er-5 d u e to u n d ern u trition a n d h igh a d u lt m o rta lity fro m n o n -co m m u n i-ca b le d isea ses a re sign ifii-ca n tly grea ter a m o n g th e lea st so cia lly fa vo red . Th e h ea lth situ a tio n is e ve n m o re d e va st a t in g if we co n sid e r t h a t p e o p le in lo we r so cio e co n o m ic gro u p s h a ve th e largest b u rd en of d isease an d th e fewest re-sou rces for ad eq u ate treatm en t. An exam p le of t h is sit u a t io n is Bra zil wh e re m o rt a lit y h a s b e e n sh o wn t o b e a p p ro xim a t e ly t h re e t im e s gre a t e r wh e n co m p a rin g t h e le a st t o t h e m o st so cia lly fa vo re d o ccu p a t io n a l ca t e go ry (Du n -can et al., 1995).
It is d ifficu lt to d ra w clea r rela tion sh ip s for th e ep id em io lo gica l a sso cia tio n b etween n o n co m m u n ica b le d ise a se s in a d u lt s a n d u n d e r -n u tritio-n i-n ch ild re-n . I-n p articu lar, it is d ifficu lt to exp lain th e h igh er in crease in ob esity in low-in com e p eop le of d evelop low-in g cou n tries, as th is p o p u la tio n still h a ve a h igh p re va le n ce o f u n -d ern u trition . Th ese h igh er rates of u n -d ern u trition are associated with m u ch lower en ergy in -ta ke s th a n in co u n trie s like th e U n ite d S-ta te s. Ove ra ll, t h e n a t io n a l d a ily p e r ca p it a ca lo rie su p p ly in Brazil, in 1996, was 1,711.2kcal, wh ere-a s in t h e U n it e d St ere-a t e s, in 1994, it were-a s 2,700 kcal (Mon teiro et al., 2000; Pu tn am , 1999). A re-ce n t stu d y in a ve ry p o o r co m m u n ity (in co m e less th a n US$1/ d a y) in No rth ea st Bra zil fo u n d o ve rwe igh t a d u lt s (17%, BMI ≥25) e a t in g le ss th an 80% of req u irem en ts (ad ju sted to statu re) (Florên cio et al., u n p u b lish ed resu lts). For th ese reason s, it is still an op en q u estion wh eth er th e p o o r o b ese a re in d eed ea tin g a n “excess of en -ergy” accord in g to req u irem en t. In sp ite of th is, o b esity is in crea sin g in p o o r p o p u la tio n s even m ore th an am on g h igh er in com e p eop le. Brazilia n n a t io n a l su rve ys, fo r e xa m p le , h a ve d e -scrib e d a m a rke d in cre a se in th e fre q u e n cy o f ob esity am on g ad u lts. Th e h igh est in crease was seen in lowest in com e wom en from th e rich est region of th e cou n try, i.e., th e Sou th east (227%, from 6.6% in 1975 to 15% in 1997). Pattern s b etween gen d ers a re very d ifferen t, a s th e p reva -len ce o f o b esity in crea ses with in co m e in m en wh ereas in wom en obesity in creases with p over-t y, b e in g h igh e r in over-t h e p o o re sover-t re gio n o f over-t h e cou n try (North east) th an in th e h igh est in com e q u a rt ile o f t h e rich e st re gio n (Mo n t e iro e t a l., 1999).
Th ese resu lts raise th e qu estion wh eth er th e in crea se in th e p reva len ce of ob esity is grea ter a m o n g p o o r p e o p le o f t ra n sit io n a l so cie t ie s, b eca u se th ese p o p u la tio n s, esp ecia lly wo m en , h ave h igh er su scep tib ility to th e d eleteriou s
ef-fects of Western lifestyle (h igh in take of an im al an d p rocessed food , low p h ysical activity, etc.). Th is h yp o t h e sis is st ill u n d e r d e b a t e , a n d o n e stro n g ca n d id a te fo r th is h igh e r su sce p tib ility se e m s t o b e e a rly u n d e rn u t rit io n , a s it co u ld p e rm a n e n t ly “p ro gra m ” t h e in d ivid u a l t o in -crease an d / or p reserve fat stores.
To ou r kn owled ge, th e first ep id em iological e vid e n ce fo r t h is h yp o t h e sis ca m e fro m t h e stu d y o f th e Seco n d Wo rld Wa r Du tch Fa m in e. As o n e o f th e m o st im p o rta n t ep id em io lo gica l sets, th is p op u lation h as b een exten sively stu d -ied . Ra velli et a l. (1976) sh o wed a n in crea se in t h e in cid e n ce o f o b e sit y in 19 ye a r-o ld m e n wh o se m o th ers su ffered fo o d d ep riva tio n d u r-in g th e first h a lf o f ge sta tio n . Su b se q u e n tly, it was sh own th at u n d ern u trition d u rin g early ges-tation was associated with h igh er BMI an d h igh -e r wa ist circu m f-e r-e n c-e in 50 y-e a r-o ld wo m -e n b u t n o lon ger in m en (Ravelli et al., 1999).
Ou r gro u p a t th e Fe d e ra l U n ive rsity o f Sã o Pa u lo h a s b e e n st u d yin g t h e a sso cia t io n b e -t we e n u n d e rn u -t ri-t io n a n d o b e si-t y in -t h e lo w-in com e p op u lation sw-in ce th e 1990s. In 1995 we d escrib ed a co existen ce o f u n d ern u tritio n a n d o b esity in a sh a n tyto wn p o p u la tio n in th e city of São Pau lo (Sawaya et al., 1995). In p articu lar, th is stu d y sh o wed a h igh p reva len ce o f u n d er-n u tritioer-n (low weigh -for-age aer-n d / or low h eigh t-fo r-a ge) in ch ild ren (30%) with a sh ift to wa rd s overweigh t an d ob esity (h igh weigh t-for-h eigh t a n d BMI) a m on g a d olescen ts (21% in girls a n d 8.8% in b o ys) a n d a d u lts (14.6%). Mo re o ve r, a h igh p revalen ce of obesity associated with stu n t-in g (t-in d icative of ch ron ic growth faltert-in g d u r-in g ch ild h o o d a n d t h e m a r-in co n se q u e n ce o f p o o r n u t rit io n in d e ve lo p in g co u n t rie s) h a s b e e n fo u n d in a n u m b e r o f p ro t o co ls o ve r t h e years, in d icatin g th at ob esity cou ld occu r in an in dividu al su bsequ en t to growth falterin g (Kosin et al., 1987; Sawaya et al., 1989, 1995). Later, oth -er stu d ies h ave rep licated th ese fin d in gs sh ow-in g a n a sso cia tio n b etween stu n tow-in g a n d o ver-we igh t in o th e r co u n trie s su ch a s Ru ssia , Ch in a, ain d Sou th Africa, all of wh ich are u in d ergo -in g n u trition al tran sition (Pop k-in et al., 1996).
A m o re re ce n t stu d y in Ala go a s, o n e o f th e p o o re st sta te s in Bra zil, fo u n d a cle a r co -e xis-t e n ce o f h igh le ve ls o f sxis-t u n xis-t in g a n d o b e sixis-t y (Florên cio et a l., 2001). Th ree h u n d red a n d fift e e n fa m ilie s (1,247 p e o p le ) livin g in fift h e o u fift skirt s o f Ma ce ió in a “h o m e le ss” p e o p le’s e n ca m p m e n t we re su rve ye d . Mo n th ly fa m ily in -com e wa s US$ 40.3 a n d p er ca p ita in -com e wa s US$ 9.6. Am o n g ch ild re n (10 ye a rs o r le ss) th e p revalen ce of u n d erweigh t (less th an -2 Z score o f w/ a ), st u n t in g (le ss t h a n -2 Z sco re o f h / a ), a n d u n d e rwe igh t p lu s stu n tin g (le ss th a n -2 Z score of w/ a an d h / a) was 3.8%, 8.3%, an d 8.7% resp ectively. A h igh p revalen ce of low BMI-for-a ge (13%, b e lo w 5t h p e rce n t ile ) BMI-for-a n d st u n t in g (11%, b e lo w -2 Z sco re o f h e igh t -fo r-a ge ) wa s fou n d am on g ad olescen ts. Overweigh t/ ob esity (6.2%, a b o ve 85t h p e rce n t ile o f BMI-fo r-a ge ) wa s se e n sp e cifica lly in girls, t re n d s fo u n d in oth er stu dies. Th e adu lts exh ibited a h igh p reva-le n ce o f o ve rwe igh t / o b e sit y (25%, BMI ≥25), b u t st u n t in g we re a lso sign ifica n t ly p re se n t (22%, less th an -2 Z score of old est age of NCHS stan d ard s). Of th e stu n ted in d ivid u als, 30% su f-fered from overweigh t/ ob esity an d 16.3% were u n d e rwe igh t. Ove rwe igh t/ o b e sity a n d u n d e r-we igh t co e xiste d in 30% o f h o u se h o ld s. Th e se resu lts su ggest th at at least in tran sition al p op -u la tio n s, o b esity m a y p o ssib ly b e o cc-u rrin g a s a seq u ela e o f u n d ern u tritio n ea rlier in life. We h a ve sp e cu la t e d in t h e p a st t h a t e a rly m a ln u tritio n resu lts in a d ecrea se in en ergy req u ire -m e n ts, a n d th a t th is -m a y p ro -m o te a te n d e n cy t o wa rd s a p o sit ive e n e rgy b a la n ce wh e n fo o d availab ility im p roves, for exam p le wh en an in -cre a se in a ge p e rm it s t h e a cce ss t o fo o d a id p ro gra m s in sch o o l o r th e a b ility to se a rch fo r fo o d a u t o n o m o u sly, a s in t h e ca se o f st re e t -ch ild re n in Bra zil, o r wh e n p o o r a d u lt s m o ve from ru ral to u rb an areas.
Th is re vie w d e scrib e s so m e o f t h e p h ysio -logical m ech an ism s fou n d to b e related to p os-it ive e n e rgy b a la n ce a n d fa t a ccu m u la t io n in p reviou sly u n d ern ou rish ed in d ivid u als.
Physiological basis for long-lasting changes in positive energy balance in previously undernourished subjects
Effects on body fatness and growth velocity
Th e re a re a la rge n u m b e r o f st u d ie s d e m o n -stra tin g m e ta b o lic a lte ra tio n s in ch ild re n su f-fe rin g fro m u n d e rn u t rit io n , in a ll t issu e s a n d b od y system s. Th e m ajority of th ese alteration s wo rk t o wa rd s e n e rgy co n se rva t io n a n d m a in -t a in in g a lo w m e -t a b o lism (Wa -t e rlo w, 1994).
H o we ve r, fe w st u d ie s h a ve in ve st iga t e d t h e p erm an en ce of su ch alteration s after n u trition a l re co ve ry. Th e re is so m e e vid e n ce fo r a d is -p ro-p ortion ately greater re-p len ish m en t of b od y fa t st o re s t h a n b o d y p ro t e in st o re s d u rin g t h e catch -u p growth in in fan ts an d ch ild ren recov-e rin g fro m u n d recov-e rn u t rit io n . In a st u d y o f t h recov-e growth rates of u n d ern ou rish ed ch ild ren , Ash -worth (1969) u sed an th rop om etric variab les to o b se rve a sp e cific in cre a se in b o d y fa t a t t h e tim e wh en th e exp ected weigh t-for-h eigh t h ad b een reach ed so th at, after recovery, p reviou sly u n d ern ou rish ed ch ild ren were fou n d to b e fat-t e r fat-t h a n we ll-n o u rish e d ch ild re n o f fat-t h e sa m e age an d weigh t. More recen t stu d ies b y Fjeld et a l. (1989) h a ve co n firm e d t h is fin d in g u sin g m etab olic b alan ce stu d ies com b in ed with m easu re m e n ts o f to ta l e n e rgy e xp e n d itu re , d e te r m in e d u sin g t h e d o u b ly la b e le d wa t e r t e ch -n iq u e, to d eterm i-n e fa t a -n d p rotei-n a ccretio-n s d u rin g we igh t ga in . Th e m e a n fa t co n t e n t in th ose stu d ies was ap p roxim ately 42% of weigh t ga in (Fjeld et a l., 1989), wh ich is n ea rly d ou b le th e e xp e cte d m e a n b o d y fa t co n te n t o f 24% in yo u n g ch ild re n (Fo m o m e t a l., 1982). In t h e sam e stu d y, it was also sh own th at th ere was n o d iffe re n ce in th e fa t co n te n t o f n e w tissu e b e -t we e n in fa n -t s ga in in g we igh -t a -t a m o d e ra -t e ra t e (6g/ kg/ d a y) o r a ra p id ra t e (12g/ kg/ d a y). Stu d ies su ch as th ese h ave n oted th at h igh en -ergy feed in g of u n d ern ou rish ed ch ild ren is rel-a t ive ly e rel-a sy, im p lyin g t h rel-a t t h e ch ild re n rel-a re h u n gr y, p e rh a p s b e ca u se t h e ir lo w b o d y fa t st o re s h a ve t rigge re d sign a ls e n co u ra gin g h y-p ery-p h agia (Zh an g et al., 1994).
n o rm a l we igh t , t h e b a la n ce o f e vid e n ce su g-gests th at at least som e an d p erh ap s th e m ajor-it y o f b o n e gro wt h t a ke s p la ce in in t e rm ajor-it t e n t sp u rts ra th e r th a n gra d u a lly o ve r tim e (La m p l e t a l., 1992) a n d is re gu la t e d b y a ch o re o -grap h ed cast of circu latin g h orm on es an d local growth factors (Nilson et al., 1994). It is th ou gh t th at m u scle growth is a n atu ral con seq u en ce of b o n e gro wth , with m u scle stretch in g a ctin g a s o n e o f t h e p rim a ry m u scle gro wt h st im u la n t s (Tira p e gu i e t a l., 1994). Th u s, in t h e n o rm a lly n o u rish e d ch ild , gro wt h ca n b e vie we d a s a n even t th at occu rs in resp on se to a d elicate b al-an ce of growth h orm on e al-an d oth er growth fac-to rs. U n d e r th e se p a rticu la r m e ta b o lic co n d i-tio n s, a rela tively h igh p ro p o ri-tio n o f b o n e a n d m u scle growth occu rs in relation to fat d ep osi-t io n . In co n osi-t ra sosi-t , wh e n we igh osi-t ga in o r gro wosi-t h occu rs in th e ab sen ce of th e correct b alan ce of growth factors, th e resu lt is a h igh er p rop ortion of fat an d a lower p rop ortion of lean tissu e th at m ore closely resem b les th e com p osition of n ew tissu e th a t occu rs in n on -growin g a d u lts wh en th ey gain weigh t (Saltzm an & Rob erts, 1995).
Th e co m b in a t io n o f t h e se st u d ie s a n d o b -se rva tio n s stro n gly su gge sts th a t ra p id we igh t ga in fo llo win g u n d ern u tritio n ca u ses ch ild ren t o b e fa t t e r a n d t o h a ve p ro p o rt io n a t e ly le ss m u scle tissu e th an a ch ild with sim ilar age an d we igh t -fo h e igh t wh o wa s n e ve r u n d e rn o u r-ish e d . Th e se su gge st io n s a re co n sist e n t wit h th e lim ited in form ation availab le at th e cu rren t tim e. Th ere is n o reason to su p p ose th at th is red u ctio n o f m u scle m a ss (re la tive to th e a ccre -tion d u rin g n orm al growth ) an d th e in crease in fa t m a ss cea ses to p ersist in th e lo n g-term fo l-lowin g u n d ern u trition .
In lin e with th e above con sideration s, it is in -terestin g to n ote th at in som e coh ort stu d ies of stu n ted ch ild ren , a m arked in crease in weigh t-fo r-h e igh t o r BMI is n o t t-fo llo we d b y in cre a se s in h eigh t-for-age (Ben efice et al., 2001; Sawaya e t a l., 1998). In a d d it io n , in o n e lo n git u d in a l st u d y, a gro u p o f st u n t e d a n d n o n -st u n t e d sch ool girls was followed for two years (Sawaya e t a l., 1998). A se rie s o f m e t a b o lic d iffe re n ce s were fou n d b etween th ese two grou p s. Stu n ted sch o o l girls in co m p a riso n t o n o n - st u n t e d o n e s, sh o we d a h igh e r su sce p t ib ilit y t o ga in we igh t -fo r-h e igh t wh e n h igh e r fa t d ie t s we re co n su m e d a n d h a d a lso h igh e r ce n t ra l fa t a c cu m u la tio n a s se e n b y h igh e r wa istto h ip ra -tio. Figu re 1 sh ows th e growth cu rve of th e two grou p s d u rin g th e follow-u p . A h igh er in crease in we igh t - fo r- h e igh t wa s o b se rve d a m o n g stu n ted girls in com p arison to n on -stu n ted .
Effects on energy balance and fat oxidation
Un til recen tly, o u r u n d ersta n d in g o f th e ca u se o f d iffe re n ce s in b o d y fa t m a ss b e t we e n in d ivid u a ls wa s p rim a rily in flu e n ce d b y t h e gu id -in g p r-in cip le of en ergy b alan ce: En ergy Stored = En ergy In tak e - En ergy Ex p en d itu re.
Th u s, it h a s b een reco gn ized th a t h igh lev-e ls o f b o d y fa t (i.lev-e ., lev-e n lev-e rgy) ca n n o t h a vlev-e b lev-e lev-e n accu m u lated with ou t en ergy in take b ein g rela tively h igh or en ergy exp en d itu re b ein g u n u su -ally low, or a com b in ation of th ese two op tion s. A n u m b er of in vestigation s h ave su ggested th at b oth excessive en ergy in take to actu al req u ire-m e n t s a n d lo w e n e rgy e xp e n d it u re ca n p la y im p o rt a n t ro le s in fa cilit a t in g e xce ssive b o d y en ergy storage in b oth ch ild ren an d ad u lts ( Je -q u ie r, 1993; Sa ltzm a n & Ro b e rts, 1995). Th e re re m a in s co n t ro ve rsy o ve r t h e e xt e n t t o wh ich h yp e rp h a gia a n d lo w e n e rgy e xp e n d it u re a re d irect cau ses of b od y en ergy gain as well as b e -in g re sp o n se s to u n d e rly-in g sign a ls th a t d rive en ergy regu lation (in clu d in g th e p u tative en er-gy sign le p t in ). H o we ve r, se ve ra l lin e s o f e vi-d e n ce su gge st t h a t e n e rgy in t a ke a n vi-d e n e rgy re gu la t io n h a ve d ire ct a s we ll a s in d ire ct e f-fects. Fo r exa m p le, less th a n h a lf o f in d ivid u a l va ria b ility in b o d y fa t co n ten t is th o u gh t to b e gen etic (Bo u ch a rd & Peru se, 1988), su ggestin g th a t en ergy in ta ke a n d en ergy exp en d itu re a re in flu e n ce d b y fa ct o rs o t h e r t h a n t h e u n d e rly-in g m etab olic d eterm rly-in an t of fatn ess. A sim ilar d ire ct e ffe ct is d e m o n st ra t e d b y in t e rve n t io n stu d ies rep ortin g ch an ges in b od y com p osition with im p osed p h ysica l a ctivity in th e exp ected d irection (i.e., in creased en ergy exp en d itu re for p h ysica l a ctivity is a sso cia te d with a d e cre a se in b od y en ergy storage) (Ballor & Keesey, 1991). More recen tly, as an exten sion of th e en ergy b a la n ce p rin cip les d eta iled a b o ve, it h a s b ee n su gge st e d t h a t b o d y ca rb o h yd ra t e a n d lip id b a la n ce s p la y a crit ica l ro le in o ve ra ll e n e rgy regu lation (Flatt, 1988, 1995). Th e b asic p rin ci-p le b e h in d t h is m o d e l o f e n e rgy re gu la t io n (wh ich is in keep in g with th e m u ch earlier glu -costatic th eory of en ergy regu lation ) is th at b al-an ces of th e p rim ary en ergy su b strates, fat al-an d carb oh yd rates, h ave to b e con sid ered sep arately (Fla tt, 1988, 1995). Th u s, en ergy b a la n ce re -q u ires th at th e b alan ce of each m ajor su b strate in d ivid u ally b e m ain tain ed con stan t sin ce: Fat Stored = Fat In tak e - Fat Ox id ation, an d Carbh yd ra t e St ored = Ca rb oCarbh yd ra t e In t a k e - Ca rb o-h yd rate Ox id ation.
q u e n t ly. Th e e sse n t ia l re q u ire m e n t o f ke y t is -su e s fo r glu co se -su gge st s t h a t sign a ls sh o u ld e xist t o e fficie n t ly m o n it o r a n d co rre ct b o d y ca rb o h yd ra t e b a la n ce . An e xt e n sio n o f t h is m o d el is th a t d ieta ry m a cro n u trien t co m p o sit io n m a y p la y a n im p o rsit a n sit ro le in d e sit e rm in -in g b o d y fa t co n ten t (Fla tt, 1988, 1995). Th is is b eca u se th e h igh er th e d ieta ry fa t co n ten t, th e m o re to ta l fo o d (a n d en ergy) n eed s to b e co n -su m e d t o m a in t a in ca rb o h yd ra t e in t a ke a n d t h e re fo re ca rb o h yd ra t e st o re s, a n d t h e fa t t e r t h e in d ivid u a l will b e co m e b e ca u se o f in -creased en ergy in take.
Su p p ort for th e im p ortan ce of n u trien t b al-an ce in th e overall regu lation of en ergy b alal-an ce can b e d erived from several sou rces. Of critical im p ortan ce, Flatt (1988, 1995) h as d em on strat-ed in m ice th at en ergy b alan ce is ad ju ststrat-ed on a d a yto d a y b a sis to m a in ta in sta b le b o d y ca r b o h yd ra te b a la n ce , th ro u gh a d a p tive flu ctu a tion s in food in ta ke, a n d severa l stu d ies in h u -m a n s h a ve in d ica t e d t h a t ca rb o h yd ra t e b a l-an ce is m ore closely regu lated th l-an fat b all-an ce (Ab b o tt et a l., 1988; Sch u tz et a l., 1989). In a d -d it io n , re -d u ce -d fa t o xi-d a t io n a s m e a su re -d b y in d ire ct ca lo rim e try h a s b e e n lin ke d p ro sp e c-tively to weigh t gain (Zu rlo et al., 1990). Fu rth er su p p ort is gain ed from stu d ies lin kin g ch an ges in b o d y fa t co n ten t to ch a n ges in fa t o xid a tio n (Sch u ltz et a l., 1992). Of releva n ce, it h a s b een sh own th at resp iratory qu otien ts (RQs) of ch ron -ically u n d ern ou rish ed ad u lts h ave h igh er b asal, 12h p o st-a b so rp tive RQs th a n we ll-n o u rish e d a d u lt s, wh ich in d ica t e s t h a t t h e se in d ivid u a ls h a ve h igh e r ra t e s o f ca rb o h yd ra t e o xid a t io n a n d lo wer ra tes o f fa t o xid a tio n (Sh etty, 1992). Th is au th or attrib u tes th e h igh RQs to two m ain factors: th e h igh carb oh yd rate in take of u n d er-n o u rish e d ier-n d ivid u a ls, a er-n d a se le ct ive u se o f ca rb o h yd ra te a s fu e l e ve n in th e p o sta b so rp -t ive , fa s-t e d s-t a -t e . Th e se le c-t ive u -t iliza -t io n o f ca rb o h yd ra te illu stra te s h o w clo se ly ca rb o h y-d rate oxiy-d ation is ay-d ju stey-d as y-d em on stratey-d b y Flatt (1988, 1995). In ad d ition , th e selective u se o f ca rb o h yd ra te a s fu el h a s o b vio u s m eta b o lica l a d va n ta ges to th e u n d ern ou rish ed in d ivid -u al sin ce carb oh yd rate (glycogen ) oxid ation resu lt s in m o re ATP ge n e ra t io n t h a n iso e n e r -ge t ic a m o u n t s o f fa t o r p ro t e in (Sh e t t y, 1999). H e n ce , it is n o t u n like ly t h a t t h e h igh fa st in g RQs of th e u n d ern ou rish ed reflect to som e d e -gre e th e m e ta b o lic e fficie n cy o f th e a ctive tis-su e s o f t h e se tis-su b je ct s b y re so rt in g t o sp e cific m e t a b o lic p a t h wa ys t h a t fa vo r m o re e fficie n t u tilization of th e availab le m etab olic fu el.
An o t h e r im p o rt a n t ca n d id a t e fo r t h e co n -trol of en ergy b alan ce in u n d ern ou rish ed in d i-vid u a ls is Re st in g En e rgy Exp e n d it u re (REE).
Exp erim en ta l sem i-sta rva tio n stu d ies o n well-n ou rish ed a d u lt h u m a well-n volu well-n teers ca rried ou t b y Ben ed ict et al. (1919), Keys et al. (1950), an d su b seq u en tly b y Gra n d e et a l. (1958), h a ve in -variab ly sh own a red u ction in REE. Th is con sis-t e n sis-t fin d in g o f a re d u ce d REE d u rin g e xp e ri-m en ta l seri-m i-sta rva tion wa s exp la in ed b oth on t h e b a sis o f a d e cre a se p er sein t h e a ct ivit y o f
th e m etab olically active tissu es of th e b od y an d as a con seq u en ce of a loss of active tissu e m ass d u e to lo ss o f b o d y weigh t. In th is co n d itio n , a d ecrease in in su lin , th yroid h orm on es, sym p a -th etic n ervou s system , an d catech olam in es h as b een d escrib ed , associated with an in crease in glu ca go n , gro wt h h o rm o n e , p ro t e in ca t a b o -lism , an d free fatty acid s (Sh etty, 1999). Stu d ies in ch ro n ica lly u n d e rn o u rish e d a d u lt s fo u n d lower REE exp ressed eith er in absolu te term s, or exp ressed p er u n it b od y su rface area, alth ou gh th ese sa m e stu d ies h a ve fa iled to d em o n stra te a n y sign ifica n t d e cre a se in m e ta b o lic ra te p e r kg of a ctive tissu e m a ss. Th ese o b serva tion s in th e ch ron ically u n d ern ou rish ed were in m arked co n t ra st t o t h e d e m o n st ra t io n o f d e cre a se in REE p e r kg o f a ct ive t issu e m a ss d u rin g se m i-st a rva t io n in we ll-n o u rish e d a d u lt s (Sh e t t y, 1999).
In ch ro n ica lly u n d e rn o u rish e d ch ild re n , d a t a a re m u ch sca rce r. On e in ve st iga t io n h a s stu d ied 58 p re-p u b erta l b o ys a n d girls a ged 8-11 ye a rs fro m t h e sh a n t yt o wn s o f Sã o Pa u lo .
Fig ure 1
Twen ty-eigh t were m ild ly stu n ted (h eigh t-fo r-age ≤-1.50 Z scores) an d 30 h ad sim ilar weigh t-for-h eigh t b u t n orm a l h eigh t (h eigh t-for-a ge > -1.50 Z scores). Paren ts of th e two grou p s were o f e q u iva le n t h e igh t a n d b o d y m a ss in d e x. In on e set of exp erim en ts, fa stin g a n d p ostp ra n -d ial en ergy exp en -d itu re, RQ, an -d su b strate oxi-d a tio n were m ea su reoxi-d b y in oxi-d irect ca lo rim etry in a 3-d ay resid en t stu d y. Com p ared to con trol ch ild ren , stu n ted ch ild ren h a d n o rm a l restin g e n e rgy e xp e n d itu re re la tive to b o d y co m p o si-tion a n d n orm a l p ost-p ra n d ia l th erm ogen esis. However, stu n ted ch ild ren sh owed sign ifican tly h igh er fa stin g RQ, a n d in co n seq u en ce fa st -in g fat oxid ation was sign ifican tly lower. It was co n clu d ed th a t ch ild h o o d n u tritio n a l stu n tin g wa s a sso cia t e d wit h lo n g-t e rm im p a irm e n t o f fa t o xid a t io n , a fa ct o r t h a t st ro n gly p re d ict s ob esity (Hoffm an et al., 2000a).
In an oth er set of exp erim en ts, free-livin g to-tal en ergy exp en ditu re (TEE) was m easu red over 7 d ays u sin g th e d ou b ly lab eled water m eth od . It was fou n d th at stu n ted girls h ad sign ifican tly lower TEE th an b oys, wh ich m ay h elp to exp lain th e p a rticu la rly h igh risk o f o b esity in stu n ted a d o le sce n t girls a n d wo m e n a s d e scrib e d in p reviou s stu d ies (Hoffm an et al., 2000b ).
In a th ird set o f exp erim en ts, th e h yp o th e -se s t h a t t h e -se n u t rit io n a lly st u n t e d ch ild re n h a d im p a ire d re gu la t io n o f e n e rgy in t a ke wa s tested . A 753 kJ yogu rt su p p lem en t was ad m in -istered at b reakfast an d its effect on d aily en er-gy in t a ke a sse sse d . Th e re we re n o d iffe re n ce s in e n e rgy in t a ke b e t we e n st u n t e d a n d n o n -stu n ted ch ild ren , even th ou gh th e -stu n ted ch il-d re n we igh e il-d 10% le ss. En e rgy in t a ke p e r kg b o d y we igh t wa s sign ifica n t ly h igh e r in t h e
stu n ted ch ild ren , a n d th e ra tio en ergy in ta ke/ re st in g e n e rgy e xp e n d it u re wa s a lso sign ifica n tly h igh er. In a d d itio n , th e a b so lu te d iffer -en ce in -en ergy in take b etwe-en su p p lem -en t an d co n t ro l d a ys wa s h igh e r in st u n t e d ch ild re n com p ared to n on -stu n ted on es (Hoffm an et al., 2000c). Th ese fin d in gs su ggest im p ortan t m etab o lic ch a n ge s p re se n t in p re vio u sly u n d e r -n o u rish e d ch ild re -n (wit h lo w h e igh t / a ge b u t n orm al weigh t/ h eigh t).
Conclusion
Evid e n ce o f a h igh e r su sce p t ib ilit y o f lo win -com e p op u lation s to ob esity is u n q u estion ab le b oth in d evelop ed an d d evelop in g cou n tries. At t h e sa m e t im e , a n in cre a sin g a m o u n t o f e vid en ce for coexisten ce of ob esity an vid u n vid ern u -t ri-t io n (a n d / o r n u -t ri-t io n a l s-t u n -t in g) in d e ve lop in g cou n tries h as b een p u b lish ed . Un d ern u t rit io n in d e ve lo p in g co u n t rie s la st s t h ro u gh -o u t gesta ti-o n , ch ild h -o -o d , a n d fr-o m -o n e gen era tio n to era n o th er, era n d th e in d ivid u era ls wh o su r -vive are very likely th e on es wh o h ave b oth th e p h ysio lo gica l a d a p ta tio n m ech a n ism s a n d en -viron m en tal con d ition s to m in im ize th e effects o f u n d e rn u t rit io n . Th is re vie w p re se n t e d e vi-d en ce of a series of p h ysiological alteration s in stu n ted in d ivid u als wh ich are in lin e with b asic re se a rch o n gro wt h ve lo cit y, fu e l u t iliza t io n , a n d e n e rgy b a la n ce . Co n sid e rin g t h e im p o r -tan ce of th e p resen t issu e for world wid e Pu b lic H e a lt h , t h e n e e d is cle a r fo r lo n git u d in a l a n d in t e rve n t io n st u d ie s t o b e t t e r in ve st iga t e t h e cau sal relation sh ip s b etween n u trition al stu n t-in g an d ob esity.
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Su b m itted on Decem b er 12, 2001
