Você está na página 1de 23

Prodigal versus Frugal Phenotype:

A Parable
Jonathan Krakoff, M.D.
Chief, Obesity and Diabetes Clinical Research Section
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes,
Digestive and Kidney Diseases
National Institutes of Health
Phoenix, Arizona
For the National Press Foundation
February 23rd, 2016

A brief overview of the NIDDK clinical research unit:


(more up close and personal views on our tour!)

Inpatient unit
Metabolic kitchen
Whole Room Indirect Calorimeters (2)
Bomb calorimetry
Automated vending machines

The Energy Balance Equation


How much energy you burn
e.g. Metabolic rate &
Physical activity

How much you eat


How much you absorb

re
it u
nd
pe
Ex

Int
e
ak

Body Weight

Measuring Energy Expenditure

1700s, Antoine-Laurent de
Lavoisier theorized:
Burning candle needs oxygen
& releases heat
So do organisms need oxygen
and release heat as they combust
food

An early example of Direct Calorimetry

Energy Expenditure
Nutrient metabolism creates energy
Extraction of chemical energy occurs via oxidation
(burning) of fuels to CO2 and H2O
Measure gas whole body O2 consumption & CO2
release
Energy production=energy liberated from oxidizing
carbohydrates + lipids + proteins
When you measure the change in 02 and C02=
Indirect Calorimetry

Indirect Calorimetry Modalities


Resting energy expenditure
Supine
Hood placed over participant

24 hour energy expenditure


Whole room indirect calorimeter (Respiratory
chamber)
Sealed room but with air in/air out
Activity is limited but not resting

Schematic of Whole Room Calorimeter

Ravussin et al. JCI 1986

Components of Energy Expenditure

Activity
related

Total
Daily EE

Thermic
effect of
food
Resting
Metabolic
Rate

Energy from
physical activity

Energy from food


consumption

Energy from organ


function

Energy Expenditure (as measured in our whole room


calorimeter) is strongly tied to body size

Bigger people
burn more energy

Weyer C et al IJO, 1999

The Thrifty Genotype/Phenotype

Proposed an underlying genotype that lead to insulin overproduction


from food intake
Important in energy conservation, as would favor adipose storage
Beneficial in times of famine
(allow hunter-gatherer populations to increase fat mass during times of food
availability for storage during food scarcity)
Overtime, this hypothesis has been revised:
Focus on evolutionary thriftiness (energy conservation)
in face of repeated famine

Energy expenditure may have a role in future weight


gain
r=-0.16, p=0.007

BUT The effect is very very modest:


So for every 100 kcal lower EE
this corresponds to only 0.2kg/yr more weight gain

Piaggi and Krakoff JCEM 2013

People do not spend their lives in energy balance


We overeat; we diet

Activity
related

Total
Daily EE

Thermic
effect of
food
Resting
Metabolic
Rate

Energy from
physical activity

What happens to EE
when we overeat?
Energy from food
consumption

Energy from organ


function

If you are a rodent: you can increase your energy expenditure


to account for overconsumption

101%
increas
e in EE

Rothwell & Stock, Nature, 1979

Energy expenditure in humans does not change


nearly as much

15
% change in Energy expenditure

10.4

10
5
0
-5
-10

-7.4

Overfeeding is a whopping 200% (2 times) what they need

Energy expenditure over 24 hours: comparison of fasting vs.


energy balance
Enter
2.4

Lunc
h

Dinner

Snac
k

2.2

Sleep

2
1.8
EE per min (kcal)
1.6
1.4
1.2
1
0:00

4:00

EU = Energy Balance
FST = fasting

8:00

12:00

Hours in calorimeter (h)

16:00

20:00

Overfeeding increases energy expenditure

2.4
2.2
2
1.8

EE per min (kcal)


1.6
1.4
1.2
1
0:00

4:00

8:00

12:00

Hours in calorimeter (h)

EU = Energy
Balance

16:00

20:00

Spendthrift vs. Thrifty Phenotypes

r=0.71,
p<0.01

Spendthrift

Thrifty
Weyer et al, Int. J. Obesity, 2001

Study outline
Oral Glucose Tolerance Test to assure did not have diabetes
Screening

Baseline

Two week period of weight maintaining diet

Acclimation whole room indirect calorimeter stay (eucaloric)


2nd eucaloric calorimeter stay for precise determination of 24 h EE in
energy balance
Indirect

Calorimetry Overfeeding (200%) and fasting chamber (in random order)

42 days
caloric
restriction

Fed 50% of weight maintaining energy needs (Ensure)


Food in duplicate collected daily for bomb calorimetry
Stool and urine collected weekly (3 days per week) for
bomb calorimetry
Actical monitors worn on wrists/ankles and at hip
continuously
Calorimeter stays weekly

Less decrease in energy expenditure with fasting was


associated with greater weight loss

r=-0.84, p=0.0006

Reinhardt & Votruba, Diabetes 2015

Study outline
Screening

Baseline

Oral Glucose Tolerance Test to assure Normal Glucose Regulation

Period on weight maintaining diet

Indirect
Calorimetry

Acclimation whole room indirect calorimeter stay (eucaloric)


2nd eucaloric calorimeter stay for precise determination of 24 h EE in
energy balance

5 x 200% overfeeding
1 Fasting
Random order
Intervention 3 day wash out period with weight maintaining diet between calorimeter
Diets
stays

@ 6 months
Long term Annual x 7 years
Follow Up

Predictors of weight change at 6 months

=0.32 kg/% EE decrease adjusted =0.42 kg/% EE increase adjusted


for baseline weight, age, sex and race for baseline weight, age, sex and
race
Schloegl, Piaggi, Thearle, Diabetes 2016review

Summary
Energy expenditure measured in energy balance
is a very weak predictor of weight gain
We have identified spendthrift and thrifty
phenotypes defined by fasting and overfeeding
which:
Identify individuals likely to do less well with caloric
restriction
Are at risk for future weight gain
Follow us on twitter: @NIDDKgov
Media contact: NIDDKMedia@niddk.nih.gov

Questions?

Você também pode gostar