http://cafescientifique.onthewight.com/prof-mark-hanson-fat-fate-obesity-talk/

1. 1

2. Consequences of childhood obesity. From Han et al (2010) Lancet
375:1737-45

3. Non-communicable disease (NCD)
• Cardiovascular disease, diabetes, chronic lung disease, some
cancers
• World’s biggest killers – 36m deaths/year, 63% of all deaths
globally. In developed countries but also -
• 80% in low- and middle income countries, especially as they
undergo socio-economic improvement following reductions in
communicable disease
• Risks of NCD exacerbated by Western lifestyle, urbanisation,
migration, increased longevity, falling postnatal mortality,
smaller family size
• WHO projects an increase of 15% in NCDs over next decade
globally
Adapted from WHO Action Plan for the Global Strategy for the Prevention and
• Preventable Control of Noncommunicable Diseases; Dr Ala Alwan, 2008
• Prevention strategy not part of the Millennium Development
Goals – but UN General Assembly held Summit in Sept ’11 to
discuss this………

4. Likelihood and severity of risks to global development

5. Daniel Lambert (1770-1809) weighed
52 st = 335 kg when he died

6. Brown or white?

8. Google “How to lose weight”
About 329,000,000 results

9. Sumithran et al NEJM
(2011) 365: 1597-604

10. The relationship between the quality of the
start to life and longer-term consequences
is not a matter of extremes
40
Prevalence of Type 2
diabetes (%)
30
20
10
0
<5.5 6.5 7.5 8.5 9.5 >9.5
Birth weight (lbs)
Godfrey, Eur J Obstet Gynecol Reprod Biol 1998;78:141-50

11. Our normal biology: of all mammals,
we are the fattest at birth.

12. What processes
influence fetal fat
deposition?
Fetal liver blood flow is
affected by mother’s diet.
It has long-
term implications for liver
metabolism,
growth factor production
and fat deposition

13. Godfrey KM et al PLoSOne

14. Pune Maternal Nutrition Study
the ‘thin-fat’ Indian newborn
SD score relative to UK newborns
0
Weight
Head
Abdomen
Length
Fat
Arm circ
-3
Adipose tissue relatively
preserved
India: 2.6 - 3.0 kg
UK white: 3.3 - 3.5 kg Yajnik CS, Int J Obesity 2003;
27: 173-80

15. 2h insulin (mU/l) Diabetes prevalence (%)
30
50
Prevention is easier if
we know the cause.
40
20 South Asian
Why does one person or
30
population group have a
higher risk than
20
another, even in the 10
same environment?
10
Genetic predisposition? European
0 0
0.8 0.9 1 0.8 0.9 1
Waist / hip ratio Waist / hip ratio
From Mckeigue et al. Lancet, 1991, 337: 382
McKeigue et al. Lancet, 1991, 337: 382

16. Genes are us?

17. The case of the missing heritability
• “When scientists opened up the human genome, they
expected to find the genetic components of common traits
and diseases. But they were nowhere to be seen……….”
Nature news feature 6 Nov 2008

18. Genetic
Epigenetic
Developmental
Environment

19. Mechanisms of inheritable epigenetics
Zaidi S K et al. Mol. Cell. Biol. 2010;30:4758-4766

21. Which tissues are available for
epigenetic analysis?

22. Epigenetic state at birth predicts body composition in childhood
PAH study children SWS children
Child’s aged 9 years aged 6 years
fat
mass 8.0 r=0.32, P=0.009
r=0.20, P=0.002
n=64
(kg) n=239
7.0
6.0
5.0
4.0
3.0
2-35% -59% -84% -100%
Degree of epigenetic change in metabolic control gene
Godfrey et al 2011 (Diabetes 60: 1528- 1534) Values are means + SEM

23. Low maternal carbohydrate intake in early pregnancy
associated with higher umbilical cord RXRA gene
promoter methylation
80
r=-0.26,
70 P=0.027,
n=64
Epigenetic change in
metabolic control gene
60
50
N.B. No
association
40 with mother’s
Lowest 2nd 3rd Highest BMI or
Maternal carbohydrate intake offspring
in early pregnancy (quartiles) birthweight
Godfrey et al 2011 (Diabetes 60: 1528- 1534)

24. • The mother’s body influences her child’s development from the
moment of conception
• Her body composition, diet and lifestyle teach her baby about the
world in which she lives.
This affects epigenetic processes
which influence her child’s risk of
disease for the rest of life.

25. Human placental glucose transfer is not
transporter limited
0.04
Glucose trasnfer to fetus
(mmol/min)
0.02
0.00
0 5 10 15 20
Maternal plasma glucose (mmol/l)
Dually-perfused term placentae. Day, Lewis et al (unpublished)

26. What is “abnormal”?
Obesity (BMI ≥ 95th percentile) at age 4 years according to
maternal first-trimester BMI
35
30 p < 0.001
Obesity (% of children)
25 ?
ical
o log
20 h
is pat
h
15 is t
W hen
10
5
0
<18.5 18.5-24.9 25-29.9 30-39.9 >40
Maternal BMI
From Whitaker, Pediatrics. 2004 Jul;114(1):e29-36.

27. Interaction between parity and mother’s body
composition
mean % body fat from skinfold thickness
in 276 men & women aged 28-31 years
35.0 Parity p=0.004
Mother’s BMI in early pregnancy p<0.001
Primiparous
% body Multiparous
fat
30.0
25.0
-21.5 -24.2 >24.15
Mother’s body mass index in Adjusted for age, sex &
early pregnancy (kg/m2 ) current smoking
Reynolds & Godfrey et al (2010)

28. Obesity and NCDs are increasing
in every country
• Interventions to promote exercise and
healthy diet often do not work for the
people most at risk
• Many people lose weight, only to gain it
again, as if their body’s weight control
systems are set to a higher level.
• These systems are set in development, so
the interventions in adult life may be too
late.

29. Current focus of action on
obesity and NCDs
• Target adult lifestyle, especially physical
exercise, diet (reduce sugar, salt, fat), alcohol
abuse
• Target multinational food industry
• Make individuals responsible for what they eat
and how much they exercise
• It’s all about choice
• Make us all feel guilty for “gluttony” and “sloth” -
even children
• If that doesn’t work, there’s surgery or drugs

31. Influences on diet
Education
Not smoking
Watching little television
Prudent
Dieting Diet
Taking strenuous exercise
Older age
Not living with children

32. Southampton Women’s Survey. Following
Southampton families. Young women with a lower
level of educational attainment are more likely to eat
an unbalanced diet
%
% 3 .5
% consuming 2 .9
% 1
.5 5% %
degrety
8 3. .4
e
an unhealthy 4 9
rsi
7% 3 1
diet 4.
Unive
5
oma
Diplonal
60%
ti
er Na
%
examel
50
s
lev
%
High
40
nced
levelmediate
s
exam
0%
Adva
3
0%
examel
s
2 Inter
v
er le
%
10
s
Low
xam
32
Educational level
0% Robinson et al EJCN 2004; 58:1174-80

33. Infant guidelines pattern score according
to prudent diet score of the mother
High 1.0
0.5
guidelines score
6 month infant
Medium 0
-0.5
Low
-1.0
to -1 to -0.5 to 0 to 0.5 to 1 >1
Low Medium High
Mother's prudent diet score
Robinson et al. Br J Nutr. 2007

34. IQ at 4 years of age in relation to infant
guidelines score
Values are mean (95% CI)
114
112
Adjusted IQ at 4 yr
110
108
106
104
102
Lowest 2 3 Highest
Standardized Infant Guidelines Score at 6 m
IQ adjusted for sex, birth order, gestational age, birth weight,
maternal age, IQ, social class, education and HOME score
Gale et al. J Child Psychol Psychiatry.
2009

35. Lifestyles of SWS women who did and did not
become pregnant within 3 months of interview
80
Not pregnant Pregnant
70
60
50
40
30
P
g
n
a
c
e
r
t
20
10
0
Not smoking > 5 portions fruit & Any strenuous activity in
vegetables per day past 3 months
Inskip et al. BMJ 2009

36. Women's compliance with nutrition and lifestyle
recommendations before pregnancy: general population
cohort study.
Inskip et al. BMJ. 2009 Feb 12;338:b481
Conclusion: Only a small proportion of women
planning a pregnancy in UK follow the
recommendations for nutrition and lifestyle
(folic acid supplement intake, alcohol
consumption, smoking, diet, and physical
activity)
and the unplanned pregnancies……?

37. Poor educational attainment
Poor diet
Take less exercise
Obese
Poorer educational
attainment
Ill-prepared for
pregnancy.
Minimal changes
in diet and health
behaviours
Greater fat mass,
less lean mass and
lower IQ at age 4 Poor infant diet
37

38. Poor educational attainment
Poor diet
Take less exercise
Obese
Poorer educational
attainment
Ill-prepared for
pregnancy.
Minimal changes
in diet and health
behaviours
Greater fat mass,
less lean mass and
lower IQ at age 4 Poor infant diet
38

39. Kain J et al (inc Simon Murphy, Cardiff Institute of Society and Health)
Obesity Prevention in Primary School Settings: evidence from
intervention studies
In Preventing Childhood Obesity. BMJ Books 2010.
“Interventions struggle to achieve changes in BMI despite
finding effectiveness on behavioural and other outcomes………
The school setting is subject to a number of barriers in
implementing sustainable obesity prevention programs,
requiring infrastructure and resources that may well not exist in
poor schools……………….Many interventions have been
criticised for focusing on the most accessible setting and
groups and for conceptualising setting as a channel of
delivery rather than a dynamic context that both shapes
and is shaped by those within it”.
39

40. Hospital-based
classroom
&
School of Medicine
Hands-on activities
+ pre and post school-based
lessons

41. Me,
my health
and my children’s
health
What do the students 41

42. How healthy are my
arteries?
Carotid artery
in the neck
The carotid
artery 42

43. 43

44. How does my lifestyle affect
my
DNA?
44

45. How was I nourished before I was
born?
Measure transport of calcium and
glucose across the placenta
45

46. 46

47. 47

48. At what age do you think your diet
starts to affect your future health?
60
***
50
percentage of respondants
40
30
20
10
0
Before you were born 0-10 11_20 Adulthood/never
Post Lifelab Lifelab peers
48
Grace et al, Health Education, Vol. 112 Iss: 6 (Date online 12/9/2012)

49. Meet
the
scienti
st

50. “A particularly successful workshop, ‘LifeLab
Southampton, is based at the local hospital and
is making an important contribution to students’
understanding of the need to adopt healthy
lifestyles.”
OFSTED 2009
“the impact of Life Lab on students’ learning and
enthusiasm for science [was judged] to be
‘Outstanding’
Senior Secondary Inspector, Southampton City Council
50

51. New Insights - Summary
• There is a very strong case for interventions in
early life for NCD prevention
• We have biomarkers of later NCD risk which can
be measured in early life
• NCD risk is graded across the entire normal
range of development
• Pre-conception period may be critical in terms of
parents’ health literacy and behaviour
• Promoting a healthy start to life means that we
could show a beneficial effect of interventions
within a short (<5 years) timeframe.

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