Why We Get Fat

Why We Get Fat
The Diet/Weight Relationship,

An Alternative Hypothesis
Gary Taubes
Wednesday, July 10, 13

Context: the obesity epidemic
6
Source: Center for Disease Control and Prevention.

And the diabetes epidemic
7
Source: Center for Disease Control and Prevention.

With obesity comes a cluster of chronic diseases

The Conventional Wisdom
“The fundamental cause of obesity and overweight is

an energy imbalance between calories consumed and
calories expended.”
The World Health Organization

Obesity is an energy balance disorder

calories in > calories out

We overeat

And the obesity epidemic?

“Increased prosperity”
A toxic “obesogenic” environment
”Toxic environment..

“Cheese-burgers and French fries, drive-in windows and supersizes,
soft drinks and candy, potato chips and cheese curls, once unusual,
are as much our background as trees, grass, and clouds… Few
children walk or bike to school; there is little physical education;
computers, video games, and televisions keep children inside and
inactive; and parents are reluctant to let children roam free to play.”
Kelly Brownell, director of the Rudd Center for Food Policy and Obesity at Yale
”Toxic environment..

Too much food, too little physical activity
Overeating
(Energy in > Energy out)
Obesity and the obesity epidemic

Too much food, too little physical activity
? Overeating
(Energy in > Energy out)
Obesity and the obesity epidemic

Counterexamples?

Sioux, South Dakota 40 % women, 10 % men, 25 % children
1928 Crow Creek “distinctly fat.” 20 % women, 25% men
Reservation and children “extremely thin”
African-Americans, 18 % of men, 30 % of women are obese

1959
Charleston, SC Total family incomes of $9 to $53/week
Zulus, Durban South 40 % adult women obese

1960
Africa Women in their 40s average 175 lbs
A third of women over 25 are obese
Obesity is a “potentially serious medical
1961-3 Trinidad problem in women”
Per capita daily diet is less than 2000
calories (21 % fat): “Fewer calories than
recommended by FAO.”
Military personnel: 22 % obese (> 120 %
ideal weight)
1963 Chile White collar workers: 32 %
Factory workers: 35 % of men, 39 %
women
“Apache women tend to be obese”

Fort Apache Indian
1963 72 % are overweight (>115% ideal weight)
Reservation, AZ
“Only 29 % of the men are fat.”
16

Bantu “pensioners”, Mean weight of women over 60 is 165 lbs.
1964-5
South Africa 30 % of women “severely overweight”
North Carolina 29 % obese (greater than 120 % ideal

1965
Cherokee weight)
25% of women and 7 % of men are obese

1969 Ghana
Half of all women in their 40s are obese
7 % of men aged 35 to 44 obese

1970 Nigeria
30 % of women 55 to 64
Raratonga, South 40 % of women obese, over 25 % “grossly

1971
Pacific obese” (>140 % ideal weight)
30 % obese, 10 % “undernourished”
Chilean factory
1974 Nearly 50% of women over 54 obese
workers
Most engaged in “heavy labor”
50% of women in their fifties are obese

Mexican-Americans 40 % of men in their forties are obese
1981 “Most inhabitants are employed in
Starr County Texas
agricultural labor and/or work in the oil
fields in the country.”
17

A modern example

Why were (are) these populations
fat?

The question, circa 1973
“It is difficult to explain the high frequency of obesity seen in a

relatively impecunious society such as exists in the West Indies,
when compared to the standard of living enjoyed in the more
developed countries… Malnutrition and subnutrition are
common disorders in the first two years of life... Subnutrition
continues in early childhood to the early teens. Obesity begins to
manifest itself in the female population from the 25th year of life
and reaches enormous proportions from 30 onwards.”
Rolf Richards, University of the West Indies


The question, circa 2005
“A few years ago, I was visiting a primary care clinic in the slums
of Sao Paulo [Brazil]. The waiting room was full of mothers with
thin, stunted young children, exhibiting the typical signs of
chronic undernutrition. Their appearance, sadly, would surprise
few who visit poor urban areas in the developing world. What
might come as a surprise is that many of the mothers holding
those under-nourished infants were themselves overweight…
The coexistence of underweight and overweight poses a
challenge to public health programs, since the aims of
programs to reduce undernutrition are obviously in conflict with
those for obesity prevention.”
Benjamin Caballero, Johns Hopkins University

More reasons to question the
energy balance hypothesis

Eating less doesn’t work
Weight loss achieved in trials of calorie-restricted diets

is “so small as to be clinically insignificant.”
Cochrane Collaboration, 2002

Eating less doesn’t work
“More than in any other illness, the physician [treating

the obese patient] is called upon only to do a special
trick, to make the patient do something – stop eating –
after it has already been proved that he cannot do it.”
Hilde Bruch, The Importance of Overweight, 1957

Exercising more doesn’t work
“It is reasonable to assume that persons with relatively

high daily energy expenditures would be less likely to
gain weight over time, compared with those who have
low energy expenditures. So far, data to support
this hypothesis are not particularly
compelling.”
AHA/ACSM 2007, Physical activity guidelines

The energy balance challenge
“Weight
management is all
about balance—
balancing the
number of calories
you consume with
the number of
calories your body
uses or `burns off.’”
The Centers for
Disease Control

A typical adult’s
food intake
2700
Kcal/day

A typical adult’s
food intake
1,000,000
Kcal/yr

A typical adult’s
food intake
10,000,000
Kcal/decade

A typical adult’s
food intake
10
tons/decade

Accuracy
required to gain
no more than 20
pounds over the
course of a
decade?

21
Kcal/day

Practicing energy balance is impossible
(20*365*10)
3500
=
21 lbs/decade

.8 % accuracy

“There is no stranger phenomena than the
maintenance of a constant body weight under marked
variation in bodily activity and food consumption.”
Du Bois, Basal Metabolism in Health and Disease, 1936

Genetics

Animal husbandry
Jersey Aberdeen Angus

Sexual variations

Puberty

Lipodystrophies
39

Paradox of progressive lipodystrophy
Overeating?
Undereating?
40

Physics

Why energy balance?
The First Law of Thermodynamics

i.e., energy conservation
∆E = Ein - Eout
Change in fat mass = Energy consumed - Energy expended
42

Why energy balance?

No arrow of causality
∆E = Ein - Eout
Change in fat mass = Energy consumed - Energy expended
43

The Alternative Hypothesis

Obesity is a disorder of excess fat accumulation
(Not energy balance, not over-eating, not sedentary
behavior)
Overeating and inactivity are compensatory effects;

they are not causes
We don’t get fat because we overeat, we overeat

because our fat tissue is accumulating excess fat.
45

The direction of causality?
∆E = Ein - Eout
CW
46

The direction of causality?
∆E = Ein - Eout
AH
47

Analogy: a growing child
2009 -- 45 lbs
2006 -- 20 lbs
48

A pathogical analogy: cancer
DAY 0 DAY 10
DAY 20 DAY 30
49 Aug 9;5:32
Cabrera, G. et al. 2006. Molecular Cancer.
Wednesday, July 10, 13 \
A history of “lipophilia”
German/Austrian hypothesis, pre-World War II
Gustav von Bergmann (1908), Julius Bauer
“More or less fully accepted” in Europe by 1940
40
50

Lipophilia
“Like a malignant tumor or like the fetus, the uterus

or the breasts of a pregnant woman, the abnormal
lipophilic tissue seizes on foodstuffs, even in the case
of undernutrition. It maintains its stock, and may
increase it independent of the requirements of the
organism. A sort of anarchy exists; the adipose tissue
lives for itself and does not fit into the precisely
regulated management of the whole organism.”
Julius Bauer, University of Vienna, 1929
41
51

Animal models?
“These mice will make

fat out of their food
under the most unlikely
circumstances, even
when half starved.”
Jean Mayer, 1968
52

If obesity is a disorder of excess fat
accumulation, what regulates fat
accumulation?
53

Adiposity 101
Triglycerides vs. fatty acids
Fat is stored as
triglycerides
Fatty acids are burned
for fuel
Fat enters and exits fat

cells as fatty acids
Inside the fat cell, fatty

acids continually cycle
into triglycerides and
back out again 54

55

Ein Eout
∆E
56

Hormonal regulation
Insulin is “the principal regulator of fat metabolism.”

Rosalyn Yalow, Solomon Berson, 1965
Frayn, K.N. 2010. Metabolic Regulation: A Human Perspective,
57
3rd edition

Hormonal regulation
Suppression of fat mobilization
Release of fatty acids from fat cells “requires only the negative
stimulus of insulin deficiency.”
Rosalyn Yalow, Solomon Berson, 1965
Frayn, K.N. 2010. Metabolic Regulation: A Human Perspective,
58 3rd edition

Insulin and fat storage, circa 2001
“The overall action of insulin

on the adipocyte is to
stimulate fat storage and
inhibit mobilization. The
remarkable effects of locally
injected insulin on the
accumulation of triglyceride
into adipocytes are graphically
illustrated in Box 2.8.”
59

Key points of fat cell regulation
When insulin is secreted or chronically elevated,
fat accumulates in the fat tissue.
When insulin levels drop, fat escapes from the fat

tissue and the fat depots shrink.
We secrete insulin primarily in response to the

carbohydrates in our diet.
“Carbohydrate is driving insulin is

driving fat.”
George Cahill, 2005
60

Textbooks?
What makes fat tissue fat?

“High blood glucose elicits the release of insulin,
which speeds the uptake of glucose by tissues and
favors the storage of fuels as glycogen and
triaglycerols, while inhibiting fatty acid mobilization
in adipose tissue.”
What makes people fat?
“To a first approximation, obesity is
the result of taking in more calories
in the diet than are expended by the
body’s energy-consuming activities.”
58
61

The Alternative Hypothesis
Like any growth defect, obesity is a

hormonal/regulatory disorder.
Like type 2 diabetes, it is fundamentally a

disorder of insulin signaling -- hence,
diabesity.
It is triggered by the carbohydrate

content of the diet

The carbohydrate content?

Refined grains, starches and sugars
Insulin secretion increases
Excess fat accumulation, obesity and the

obesity epidemic

Should this be surprising?
The conventional wisdom
1825-1965
“Every woman knows that carbohydrates are fattening,

this is a piece of common knowledge, which few
nutritionists would dispute.”
British Journal of Nutrition, 1963
65

A Diet for Obesity, 1951
Foods to be avoided: You can eat as much as

you like of the following
1. Bread, and everything else foods:
made with flour…
2. Cereals, including breakfast 1. Meat, fish, birds
cereals and milk puddings 2. All green vegetables
3. Potatoes and all other white 3. Eggs, dried or fresh
root vegetables 4. Cheese
4. Foods containing much sugar 5. Fruit…except bananas and
5. All sweets… grapes
Raymond Greene, The Practice of Endocrinology

66

Conclusions
I
Obesity is a disorder of fat accumulation, not energy
balance (not overeating and sedentary behavior).
II
Fat accumulation is regulated fundamentally by insulin and
dietary carbohydrates -- “carbohydrate is driving insulin is
driving fat.”
III
The solution to obesity and the obesity epidemics is not
getting people to move more and eat less, but restricting
the causative agent -- i.e., the
67
refined grains and sugars.
Why were those populations fat?
“Most third world countries have a high carbohydrate

intake as their economic dependence is predominantly
agricultural, with a heavy dependence on non-dairy
produces. It is conceivable that the ready availability of
starch in preference to animal protein, contributing as it
must the main caloric requirements of these populations,
leads to increased lipogenesis and the development of
obesity..”

Rolf Richards, University of the West Indies, Kingston
Jamaica, 1973
69

The catch
“...insulin regulation of
plasma FFA turnover/
oxidation is maximally
manifest at low
physiological plasma
insulin concentrations....”
Bonadonna et al. 1990. Dose dependent effect of insulin on plasma free fatty acid turnover
and oxidation in humans. Am. J. Physiol. 259:E736-750.

Red meat, obesity and diabetes?

Diet trials (2007)
A TO Z Trial

2 months

Group
n
kcal/d
CHO
PRO
FAT
Weight
LDL
Trig
HDL
DBP
Atkins
77
1381
~62g
97
84
-4.3 kg
+2.3
-52.3
-0.4
-2.9
Zone
79
1455
152
87
57
-2.0 kg
-5.3
-24.8
-0.5
-2.1
LEARN
79
1476
180
73
49
-2.8 kg
-7.3
-17.2
-3.8
-1.4
Ornish
76
1408
220
60
33
-2.8 kg
-10.1
-10.9
-5.3
-0.4
12 months
Group
n
kcal/d
CHO
PRO
FAT
Weight
LDL
Trig
HDL
DBP
Atkins
77
1599
~140g
84
78
-4.5 kg
+0.8
-29.3
+4.9
-4.4
Zone
79
1594
179
80
62
-1.5 kg
0
-4.2
+2.2
-2.1
LEARN
79
1654
194
79
61
-2.5 kg
+0.6
-14.6
-2.8
-2.2
Ornish
76
1505
195
68
50
-2.4 kg
-3.8
-14.9
0
-0.7
Gardner et al. 2007. JAMA. March 7;969-77

Diet trials (2008)
Workplace Diet Trial
Test Low Fat Mediterranean Low Carb.
Systolic BP, mm Hg -4.3 -5.5 -3.9
Diastolic BP, mm Hg -0.9 -2.2 -0.8
LDL-C, mg/dl -0.05 -5.6 -3.0
HDL-C, mg/dl 6.3 6.4 8.4
Triglyceride, mg/dl -2.8 -21.8 -23.7
T Chol : HDL ratio -0.6 -0.9 -1.1
Hemoglobin A1c, % -0.4 -0.5 -0.9
C-reactive protein, mg/l -0.6 -0.9 -1.3
Shai et al. 2008. NEJM. Jul 17;229-41 Red denotes p<0.05 for within-group change from baseline.
Purple denotes p<0.05 for comparison of Low Carb vs Low Fat.

CALORIES OR CARBOHYDRATES?
- 570 kcal à
- 330 kcal à
- 170 kcal à
76
Shai et al. NEJM. 2008.

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The Diet/Weight Relationship,

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

“The fundamental cause of obesity and overweight is

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

A toxic “obesogenic” environment

Wednesday, July 10, 13

Wednesday, July 10, 13

Obesity and the obesity epidemic

Wednesday, July 10, 13

Obesity and the obesity epidemic

Wednesday, July 10, 13

Wednesday, July 10, 13

African-Americans, 18 % of men, 30 % of women are obese

Zulus, Durban South 40 % adult women obese

“Apache women tend to be obese”

Wednesday, July 10, 13

North Carolina 29 % obese (greater than 120 % ideal

25% of women and 7 % of men are obese

7 % of men aged 35 to 44 obese

Raratonga, South 40 % of women obese, over 25 % “grossly

50% of women in their fifties are obese

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

“It is difficult to explain the high frequency of obesity seen in a

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Weight loss achieved in trials of calorie-restricted diets

Wednesday, July 10, 13

“More than in any other illness, the physician [treating

Wednesday, July 10, 13

“It is reasonable to assume that persons with relatively

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Jersey Aberdeen Angus

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

Wednesday, July 10, 13

The First Law of Thermodynamics

Wednesday, July 10, 13

The First Law of Thermodynamics