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IB35ac Human Biological Variation

10/13/2015

Obesity Trends* Among U.S. Adults
BRFSS, 1990, 2000, 2010

IB35 Human Biological Variation
Lecture #14

(*BMI 30, or about 30 lbs. overweight for 5’4” person)
2000

1990

2010

Topic for today:
Obesity
No Data

Measuring Body Fat
• Hydrodensitometry (underwater weighing)
– Measures whole body density by determining
body volume

• Calipers (anthropometry – skinfold
measurements)
• DEXA (dual energey x-ray absorptiometry)
– Whole body scanner that has two low dose xrays at different sources that read bone and
soft tissue mass simultaneously

copyright, Prof. L. Hlusko, UC Berkeley

<10%

10%–14%

15%–19%

20%–24%

25%–29%

≥30%

BMI: The Body Mass Index
BMI Categories
Underweight < 18.5
Normal weight = 18.5 – 24.6
Overweight = 25 – 29.9
Obesity > 30

www.nhlbisupport.com/bmi

5’2” 100lbs BMI = 18.3
5’2” 120lbs BMI = 21.9
5’2” 140lbs BMI = 25.6
5’8” 120lbs BMI = 18.2
5’8” 150lbs BMI = 22.8
5’8” 180lbs BMI = 27.4
6’2” 140lbs BMI = 18.0
6’2” 150lbs BMI = 19.3
6’2” 200lbs BMI = 25.7

1

IB35ac Human Biological Variation

10/13/2015

The Health Risks of Obesity









Heart disease and stroke
High blood pressure
Diabetes
Cancer
Gallbladder disease and gallstones
Osteoarthritis
Gout
Breathing problems, such as sleep apnea (when
a person stops breathing for a short time during
sleep) and asthma

2008 diabetes occurrence map

Diabetes








Insulin is a hormone that takes sugar (glucose) from the blood into
cells.
Diabetes is when you have too much glucose in the blood stream.
Type 1
– 5-10% of people with diabetes
– “juvenile diabetes”
– Body does not produce insulin
Type 2
– Most common form
– “adult onset” (diabetes mellitus)
– Body does not produce enough insulin or cells are resistant to it
Gestational

The Health Risks of Obesity
Table 1. Prevalence of Medical Conditions
by Body Mass Index (BMI) for Men
Medical Condition

Body Mass Index
18.5 to 24.9

25 to 29.9

30 to 34.9

> 40

Prevalence Ratio (%)
Type 2 Diabetes

2.03

4.93

10.10

10.65

Coronary Heart Disease

8.84

9.60

16.01

13.97

High Blood Pressure

23.47

34.16

48.95

64.53

Osteoarthritis

2.59

4.55

4.66

10.04

Source: NHANES III, 1988 - 1994.

Table 2. Prevalence of Medical Conditions
by Body Mass Index (BMI) for Women
Medical Condition

Body Mass Index
18.5 to 24.9

25 to 29.9

30 to 34.9

> 40

Prevalence Ratio (%)

Numbers in 2011:
25.8 million people affected
8.3% of the population
18.8 million diagnosed; 7.0 million undiagnosed
http://www.cdc.gov/about/stateofcdc/html/2008/Science02Diabetes.htm

copyright, Prof. L. Hlusko, UC Berkeley

Type 2 Diabetes

2.38

7.12

7.24

19.89

Coronary Heart Disease

6.87

11.13

12.56

19.22

High Blood Pressure

23.26

38.77

47.95

63.16

Osteoarthritis

5.22

8.51

9.94

17.19

Source: NHANES III, 1988 - 1994.

From: http://www.obesity.org/subs/fastfacts/Health_Effects.shtml

2

IB35ac Human Biological Variation

10/13/2015

Obesity & Fertility
• Numerous studies have shown that obese women (BMI
of 30-40) are 25-45% less likely to conceive than are
normal weight or overweight women.
• Danish study of 47,835 couples found that if both
partners were obese it took them 3 times longer to
conceive, and 1.5 times longer if both partners were
overweight.
• An overweight woman is at much higher risk for:





Gestational diabetes
Neural tube defects
Macrosomia (newborn with excessive weight, ~9-10lbs))
Low Apgar scores

Evolution of the
Human Lifestyle & Diet
• Similar to hunter-gatherers
• And then the Neolithic

copyright, Prof. L. Hlusko, UC Berkeley

Types of Genetic Effects
• Monogenic
– Dominant
– Codominant
– Recessive

• Oligogenic
• Complex Traits






Polygenic
Age affects
Gene-by-environment interaction
Gene-by-sex interaction
Environment-by-sex interaction

Consequences of the Neolithic
• Transition was accompanied by major
changes in diet for most human
populations
• Traits that were previously beneficial
became harmful in the changed nutritional
environment

3

IB35ac Human Biological Variation

Evolutionary Hypothesis
• Pandemic of obesity is caused by a
profound mismatch between humanity’s
present environmental circumstances and
those that have molded evolutionary
selection

Example: Oceanic Populations

10/13/2015

The “Thrifty” Genotype
• 1962, James Neel
• Noninsulin dependent diabetes mellitus is the result of a
thrifty genotype rendered detrimental by cultural change
• Metabolic efficiency in storage of excess calories is
achieved through over-secretion of insulin which
increases fat tissue formation and the accumulation of an
energy store.
• Rapid release of the hormone insulin in response to
elevated blood-sugar levels (hyperglycemia) was
advantageous to our ancestors, allowing them to build up
fat deposits in times of plenty
• In an environment where there is overabundant food, this
rapid response is detrimental – overproduction of insulin
leads to insulin resistance, subsequent high levels of
blood glucose, and the set of debilitating symptoms
constituting diabetes

Who else may have this “thrifty”
genotype?

Bindon JR, and Baker PT. 1997. Am J Phys Anthropol 104:201-210.

copyright, Prof. L. Hlusko, UC Berkeley

4

IB35ac Human Biological Variation

New term: Epigenetics
• The study of the mechanisms by which
genes bring about their phenotpic effects.
• The study of heritable changes in gene
function that occur without a change in the
sequence of the DNA.

Evidence for the influence of
epigenetics on obesity
• Smith et al. 2009. Journal of Clinical
Endocrinology and Metabolism 94:4275-4283.
• Studied 49 mothers who had lost ~36% of their
body weight through bariatric weightloss
surgery.
• Gestational weight gain was significantly less
(~7kg compared to 13kg).
• After surgery the number of pregnancy
complications reduced.

copyright, Prof. L. Hlusko, UC Berkeley

10/13/2015

The “Thrifty” Phenotype
• The fetus adapts to maternal malnutrition by
itself becoming nutritionally thrifty, resulting in
decreased growth, hormonal and metabolic
adaptations, and altered growth and function in
the cells of the pancreas responsible for insulin
secretion
• Over-nutrition later in life makes this
developmental adaptation disadvantageous, as
it predisposes to NIDDM through reduced
secretion of insulin or insulin resistance

Biliopancreatic diversion
bariatric surgery

In a biliopancreatic diversion, a portion of the stomach is removed. The
remaining portion of the stomach is connected to the lower portion of the
small intestine. The food you eat then bypasses much of the small intestine,
resulting in fewer calories absorbed and weight loss.
http://www.webmd.com/diet/weight-loss-surgery/biliopancreatic-diversion-1920

5

IB35ac Human Biological Variation

10/13/2015

More evidence for the influence
of epigenetics on obesity
Phenotype

Children born
before surgery

Chidren born
after surgery

Statisticaly
Significant?
No

Sex

26/28

24/33

Birth weight (kg)

3.3 ± 0.1

2.9 ± 0.1

Yes

Birth length (cm)

50.0 ± 0.7

49.1 ± 0.4

No

BMI percentile (%)

79.4 ± 3.4

68.4 ± 4.0

Yes

Height percentile (%) 50.0 ± 3.8

50.3 ± 3.7

No

A provocative new hypothesis:
• Obesity in infants has risen by 73% since 1980
• Hormome-mimicking pollutants
– Turn more precursor cells into fat cells in the
developing fetus
– Alter metabolic rate so body hoards calories
• For example: bisphenol A (used in plastic)
– in culture, this chemical caused some cells to
turn into fat cells, and caused fat cells to
proliferate

• OBESOGENS
From Table 1 in Smith et al. 2009. Journal of Clinical Endocrinology and Metabolism 94:4275-4283.

And then there are the bacteria
• Microbiome
• The gut microbiome of mice
– The obese microbiome has an increased
capacity to harvest energy from the diet.
– This is transmissible.
– 2 of 70 divisions within bacteria make up 90%
of the distal gut microbiome of mice
• Bacteroidetes
• Firmicutes
– Increased proportion of this one correlates with obesity

copyright, Prof. L. Hlusko, UC Berkeley

And then there are the bacteria
• Microbiome
• The gut microbiome of mice
• The gut microbiome of people
– 300 Danish people
• Low bacterial richness correlated with higher levels
of adiposity and inflammation-associated
characteristics

– 38 obese & 11 overweight French people
• People with low bacterial richness responded more
readily to dietary intervention

6

IB35ac Human Biological Variation

antibiotics

10/13/2015

Conclusions
• An evolutionary perspective can explain why
some common genotypes may exist despite
seeming maladaptive, and why they may be
found at higher frequencies in some populations
• Complex traits are influence by multiple genes
and multiple environmental affects. The
interplay of these factors in one population may
be quite different from their interactions in
another population.

H.J. Flint. Nature 488, 601–602 (30 August 2012)

copyright, Prof. L. Hlusko, UC Berkeley

Humans vary. Evolution played a role in that.

7

IB35ac Human Biological Variation

IB35 Human Biological Variation
Class #16

Topics for today:
Blood & Disease
How disease has affected
the pattern of human variation

Sickle Cell Anemia

10/15/2015

Topics for Today
• Looking more into founders & affected
phenotypes
• Sickle cell anemia & the discovery of
molecular diseases
• The complexity of blood
– ABO
– Rh+ and Rh– Disease susceptibility and resistance

What causes RBCs to sickle?

classic example
simple genetic disorder

Missense mutation = abnormal hemoglobin

Copyright: Prof. L. Hlusko, UC Berkeley

1

IB35ac Human Biological Variation

10/15/2015

What causes RBCs to sickle?

What causes RBCs to sickle?

6th amino acid β chain hemoglobin

Glutamic Acid
hydrophilic

HbA

Valine

HbS hemoglobin
crystallizes into long
rods within RBCs
when deoxygenated.

hydrophobic

HbS

What causes RBCs to sickle?

Missense mutation = abnormal hemoglobin

Copyright: Prof. L. Hlusko, UC Berkeley

2


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