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The Thrifty Genotype and the development of modern chronic disease

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Exercise, Diet, and Human Evolution The Thrifty Genotype and the development of modern chronic disease Lecture overview Lecture 1: Introduction to the Thrifty ... – PowerPoint PPT presentation

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Title: The Thrifty Genotype and the development of modern chronic disease


1
Exercise, Diet, and Human Evolution
  • The Thrifty Genotype and the development of
    modern chronic disease

2
Lecture overview
  • Lecture 1 Introduction to the Thrifty Genotype
    Hypothesis - genetic mismatch
  • Lecture 2 The endurance athlete as Paleo man

3
Evolution of the human genome
  • Paleolithic period
  • Little change in the genome during the past
    10,000 years
  • Hunter-gatherer societies
  • Physical activity linked to food procurement and
    survival

4
Current food procurement strategies
5
Evolution of the human form
6
Obesity Trends Among U.S. AdultsBRFSS, 1990,
1998, 2007
(BMI ?30, or about 30 lbs. overweight for 54
person)
1998
1990
2007
No Data lt10 1014
1519 2024 2529
30
Slide source CDC
7
Obesity increases the risk of disease development
  • Coronary heart disease
  • Type 2 diabetes
  • Cancers
  • Hypertension
  • Dyslipidemia
  • Stroke
  • Liver and Gallbladder disease
  • Sleep apnea and respiratory problems
  • Osteoarthritis
  • Gynecological problems (abnormal menses,
    infertility)

8
Chronic disease in modern humans - an
epidemicWhat is the underlying cause?
9
Modern humans and our paleo genome - mismatched?
  • Dietary differences
  • Food type
  • Food availability
  • Activity differences
  • Food procurement not dependent on activity
  • Physically fit genes for a sedentary lifestyle

10
Dietary Differences The modern pyramid vs. The
paleo pyramid
No grains (31 TEI) No dairy (14 TEI) No sugar
(5-10 TEI) No oil (4 TEI)
11
Activity differences
  • Activity obligatory b/c of food procurement
  • Modern H-G tribes - 8 hrs/day
  • Exercise today -
  • lt 30min/day for 70 of US population

12
Prevalence of diabetes in modern H-G tribes is 1
Genetic mismatch between our Paleo genome and
modern lifestyle
13
The Thrifty Genotype Hypothesis Neel, 1962
  • Genotypes selected into the human genome because
    of selective advantage - famine
  • Thrifty genes are exceptionally efficient in
    the intake and/or utilization of food
  • Sedentary lifestyle and constant food
    availability have disrupted gene-environment
    interactions resulting in modern chronic disease

14
Thrifty genotype hypothesis and metabolic cycling
Feast
Famine
Thrifty genes operate cyclically to process fuel
sources in a manner that would maximize survival
during food shortages
15
Thrifty genes regulate intake, storage, and usage
of glycogen and triglycerides
Thriftier storage increased probability of
survival through next famine activity phase
Negative Caloric Balance
Positive Caloric Balance
Physical Inactivity
Physical Activity
Adapted from Chakravarthy and Booth, 2004
16
So, where does modern disease come in?
X
Positive Caloric Balance
Negative Caloric Balance
Physical Inactivity
Physical Activity
Adapted from Chakravarthy and Booth, 2004
17
Can physical activity rescue this stall?
Physical Inactivity
Adapted from Chakravarthy and Booth, 2004
18
The example of insulin dysfunction
Type II - 90-95 of US diabetics At least 60
identified genetic factors Heterogeneous causes
with similar outcome Insulin dysfunction
19
Measures of Insulin Dysfunction
Glucose Tolerance Test - measures insulin response
20
Can exercise rescue our metabolic stall
Mouse model of diet- induced obesity and exercise
21
Physiological evidence from a mouse model of
diet-induced obesity
Mice fed a high fat diet (HFD) gained more body
weight than chow-fed mice Exercise reduced this
weight gain in both groups, with
greater reduction in HFD group
Am J Physiol Endocrinol Metab 295 E586-E594,
2008. First published June 24, 2008
22
Both HFD and chow fed mice that exercise have
lower fat mass Exercise groups of both dietary
treatments also consume more calories
Am J Physiol Endocrinol Metab 295 E586-E594,
2008. First published June 24, 2008
23
HFD - dashed line
Exercise improved glucose tolerance,
particularly in HFD group
CHOW - solid line
Fasting insulin was reduced by exercise
Exercise improved insulin sensitivity to similar
levels for both diets
24
What about the impact of exercise in humans?
25
Exercise may rescue the stall - what about
caloric restriction?
X
Caloric Restriction?
Physical Inactivity
Adapted from Chakravarthy and Booth, 2004
26
Caloric restriction improves glucose tolerance
and insulin action
This impact is similar to the impact of exercise
27
Physical activity and caloric restriction rescue
metabolic stall
Physical Inactivity
Caloric Balance Cycling
Adapted from Chakravarthy and Booth, 2004
28
The endurance athlete - a modern example of
Paleolithic humans
Feast
Famine
Monday Endurance nutrition with an evolutionary
twist
29
Questions/Comments?
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