J Physiol 587.14 (2009) pp 3423–3424 3423

JOURNAL CLUB

Maternal nutritional historypredicts obesity in adultoffspring independentof postnatal diet

Margie H. Davenport1 andMarta Rodriguez Cabrero2

1R. Samuel McLaughlin FoundationExercise and Pregnancy Lab, School ofKinesiology, The University of WesternOntario, London, Ontario, Canada,N6A 3K72Department of Health and HumanPerformance, Faculty of PhysicalActivity and Sport Sciences – INEF,Universidad Politecnica de Madrid, CiudadUniversitaria, Madrid 28040, Spain

Email: mdavenp@uwo.ca

In the mid-1980s, Dr David Barker begana new field of work examining the impactof events that occurred during pregnancyon the long-term health of the fetus. Thiswork led to the theory of DevelopmentalOrigins of Health and Disease (DOHaD).Since that time, researchers have foundrobust epidemiological links between fetalenvironment and long-term health. Muchof the original research into DOHaDcentred around the effects of under-nutrition. With the rising prevalence ofmaternal obesity and the hypercaloricenvironment of most developed countries,more recent studies have examined theeffects of overnutrition on the developmentof diabetes, cardiovascular disease andobesity. Studies in humans have shownthat the offspring of obese mothers arealso more likely to be obese (Gale et al.2007). However, the mechanism for thistransfer of risk from mother to child iscurrently unknown. The relatively quickrise in the obesity epidemic suggests thatenvironmental and/or epigenetic influencesare at the root of the problem rather than amajor shift in the genome in keeping withDOHaD.

In a recent issue of The Journal ofPhysiology, Howie et al. (2009) examinedthe long-term impact of a moderatelyhigh fat diet during preconception and/orpregnancy and lactation on postnatalgrowth and metabolism of the offspring

from birth to adulthood. After weaning,the authors assigned 24 weight-matchedvirgin Wistar rats to one of three groups:(1) controls (Cont) where dams were feda standard chow diet throughout life; (2)maternal high fat (MHF) where dams werefed a high fat diet throughout life; or (3)pregnancy and lactation high fat (PLHF)where dams were fed a chow diet fromweaning to conception and a high fat dietduring pregnancy and lactation. At post-natal day 110, the dams underwent dualenergy X-ray absorptiometry (DEXA) toassess body fat. Ten days later they weremated. Throughout gestation and lactation,the dams were weighed and food intake wasmeasured on a daily basis. After delivery,the litter size was culled to eight pups (4male and 4 female) who were weighed every3 days until weaning. After weaning, plasmainsulin and leptin levels were measuredin the dams following an overnight fast.After weaning, the offspring were randomlyassigned to a high fat or chow diet ad libitum.On day 150 body composition was assessedvia DEXA in the offspring. Ten days laterthe offspring were killed to measure leptin,glucose and insulin concentrations.

This study is the first to examine theeffect of a maternal high fat diet on criticaltime points during fetal development andpost-weaning on long-term obesity inthe offspring. The major findings of thisstudy were: (1) the offspring of damsfed a high fat diet during pregnancy andlactation had significantly smaller pups;(2) a post-weaning high fat diet increasedadiposity in all groups but the offspringwhose dams were fed a high fat diet duringpregnancy and lactation (MHF and PLHF)had elevated adiposity compared to Contregardless of post-weaning diet; (3) thisincreased adiposity was accompanied byhyperinsulinaemia and hyperleptinaemia;and (4) maternal pre-conceptual diet didnot impact offspring adiposity.

The authors suggest that it is thediet in pregnancy and lactation, notpre-conception, that is the importantinfluence on the long-term health of theoffspring. Recently Bayol et al. (2008)examined the impact of a ‘junk food’ dietduring pregnancy and lactation on adiposityof the offspring. These authors found that amaternal junk food diet increased adiposityin the offspring (at 70 days post delivery).

They found that the adiposity that occursas a result of a maternal junk food dietis not reversed when the offspring are feda chow diet after weaning. The combinedresults of these two studies could have majorimplications for prevention of childhoodobesity. Lifestyle interventions that beginduring pregnancy which emphasize healthyeating may be able to break the trans-generational risk of obese mothers raisingobese children. However, in order to moreconclusively demonstrate the importanceof a healthy diet during pregnancy andlactation, a fourth group should be addedto the study by Howie et al. (2009). Thispotential fourth group would be placed ona high fat pre-conceptual diet followed by achow diet during pregnancy and lactation.If offspring adiposity is unchanged fromthe Cont group or lower than the MHFand PLHF groups, this would lend strongsupport to dietary interventions in thepregnancy and lactation period to preventchildhood obesity.

It was unfortunate that maternal glucosewas not measured during pregnancy (Howieet al. 2009). Although the authors suggestthat gestational diabetes can be ruled outin the MHF and PLHF groups sincethe offspring were not macrosomic, ithas been shown in human populationsthat pregnancies affected by gestationaldiabetes can result in growth-restrictedinfants. In addition, maternal obesityper se has been found to adverselyaffect glucose metabolism in the offspring(Chen et al. 2008). Although glucoselevels were not different for offspringgroups in adulthood, glucose levels werenot measured immediately after delivery(Howie et al. 2009). Alternatively, thefinding of smaller offspring could be areflection of the composition (fat, proteinand carbohydrate) of the maternal diet. Adiet that is high in fat means that it is lowerin carbohydrates and/or protein. Studiesexamining the effects of a low proteinmaternal diet indicate that the offspringare of a lower birth weight than thosewhose mothers ate sufficient protein duringpregnancy. Since the composition of thehigh fat maternal diet was not reported, thispossibility cannot be ruled out.

Leptin and insulin resistance is a commonphenotype of diet-induced obesity. Leptinworks with insulin to directly affect the

C© 2009 The Authors. Journal compilation C© 2009 The Physiological Society DOI: 10.1113/jphysiol.2009.174896

3424 Journal Club J Physiol 587.14

hypothalamic regulation of appetite (Chenet al. 2008). The adult offspring of MHFand PLHF dams in the present studywere both hyperinsulinaemic and hyper-leptinaemic indicating resistance to thesehormones (Howie et al. 2009). However,2 days after delivery the offspring of MHFand PLHF dams exhibited suppressed leptinand insulin. Although these finding areof interest, they do not provide insightinto the role that leptin and insulin mayplay in the development of adiposity inthe offspring. The authors note that theyare currently investigating this relationship;however, Chen et al. (2008) examined theeffect of a maternal high fat diet on offspringappetite regulation and metabolism at20 days after delivery. These authors foundthat maternal obesity caused programmingin utero of the brain appetite centres viaincreases in neuropeptide Y and decreases inproopiomelanocortin (POMC) potentiallythrough regulation via leptin. Offspringappetite is set within weeks after deliveryand low levels of leptin can programmethe brain appetite centres to increaseappetite throughout life. Bouret et al.(2004) demonstrated that administrationof leptin soon after delivery could preventthe programming of increased appetite;however, administration in adulthood hadno effect. These results indicate thatthere are critical periods during offspringdevelopment (pregnancy and the early post-

partum period) for the development ofappetite regulation.

Howie et al. (2009) found that the relativepregnancy weight gain was not differentbetween the three groups. As a result theysuggest that it is the composition of thematernal diet rather than excess caloricintake resulting in an elevated pregnancyweight gain that affects offspring obesity.However, in humans there are guidelinesfor maternal weight gain set by the Instituteof Medicine in 1990 which recommendsa decreased maternal weight gain withincreasing BMI. Since dams who were feda high fat diet before conception startedpregnancy at a higher body mass, it couldbe suggested that these dams should havegained less weight during pregnancy and thefinding that they gained the same amountof weight was actually detrimental. Theauthors’ suggestion that composition (fat,protein and carbohydrate) of the maternaldiet is more important than maternalweight gain in determining offspringobesity requires further investigation.Future studies examining the effect ofa maternal hypercaloric, normal fat dietcompared to a normal caloric, high fatdiet on offspring obesity during adulthoodwould be interesting.

In summary, the authors are to becommended for their investigation of theinfluence of a maternal high fat diet onthe long-term outcome of the offspring.

This information suggests that dietary inter-ventions that begin after conception couldhave a profound impact on the long-termhealth of the offspring.

References

Bayol SA, Simbi BH, Bertrand JA & SticklandNC (2008). Offspring from mothers fed a‘junk food’ diet in pregnancy and lactationexhibit exacerbated adiposity that is morepronounced in females. J Physiol 586,2319–3230.

Bouret SG, Draper SJ & Simerly RB (2004).Trophic action of leptin on hypothalamicneurons that regulate feeding. Science 304,108–110.

Chen H, Simar D, Lambert K, Mercier J &Morris MJ (2008). Maternal and postnatalovernutrition differentially impact appetiteregulators and fuel metabolism. Endocrinology149, 5348–5356.

Gale CR, Javaid MK, Robinson SM, Godfrey KM& Cooper C (2007). Maternal size inpregnancy and body composition in children.J Clin Endocrinol Metab 92, 3904–3911.

Howie GJ, Sloboda DM, Kamal T & Vickers MH(2009). Maternal nutritional history predictsobesity in adult offspring independent ofpostnatal diet. J Physiol 587, 905–915.

Acknowledgements

We would like to thank Dr Michelle Mottola forher critical evaluation of this manuscript. M. H.Davenport is funded by a Canadian Institutes ofHealth Research Doctoral Scholarship.

C© 2009 The Authors. Journal compilation C© 2009 The Physiological Society