Download Timothy A. Gilbertson, Ph.D. Biology & The Center for Advanced Nutrition

Timothy A. Gilbertson, Ph.D.
Biology & The Center for Advanced Nutrition
Utah State University
OBESITY:
™ the epidemic of obesity
™ the cost of obesity
th
t f b it
™ the causes of obesity
™ the cure… and
the cure
and
™ why doesn’t it work ?
TASTE BUDS & OBESITY
™ the role of taste ‐ a good system gone awry ?
h
ff
™ the taste of fat
™ the particular problem of fat
™ how can we control this ?
how can we control this ?
Obesity Trends* Among U.S. Adults: 1985-2007
(
BMI ≥30, or ~ 30 lbs. overweight for 5’
5 4”
4 person)
(*BMI
key
No Data
<10%
10%–14%
Obesity Trends* Among U.S. Adults: 1985-2007
(
BMI ≥30, or ~ 30 lbs. overweight for 5’
5 4”
4 person)
(*BMI
key
No Data
<10%
10%–14%
15%–19%
20%–24%
25% 29%
25%–29%
≥30%
22 y
… if Michelangelo were alive today:
Why the concern over the rise in obesity?
health effects of obesity
ƒ hypertension
h
t
i
ƒ diabetes
ƒ heart disease
ƒ end stage renal disease
ƒ joint problems
p apnea
p
ƒ sleep
ƒ cancer
ƒ metabolic syndrome
h
i l effects
ff t
ƒ psychosocial
>300,000 premature deaths/year
"Despite obesity having strong genetic
determinants the genetic composition of the
determinants,
population does not change rapidly. Therefore,
the large increase in . . . [obesity] must reflect
major changes in non-genetic factors."
Hill, James O., and Trowbridge, Frederick L.
Childhood obesity: future directions and research
priorities. Pediatrics. 1998; Supplement: 571.
CAUSES OF OBESITY
LIFESTYLE CHOICES
eat too much; exercise too little
SOCIOECONOMIC FACTORS
education level; food cost
METABOLIC DISORDERS
GENETIC FACTORS
obesity linked directly to genes
differences in energy expenditure
OBESITY: a simple cure
food intake (calories in)
Energy Balance =
energy expenditure (calories out)
positive energy balance
(weight gain)
negative energy balance
(weight loss)
eat less, exercise more
Why don’t we CHOOSE to do this ?
if we know this, why aren’t we all thin?
food intake
E
Energy
B l
Balance
=
energy expenditure
1950
1990
20xx?
20 ?
if we know this, why aren’t we all thin?
food intake
E
Energy
B l
Balance
=
energy expenditure
…a problem of choice
LIFESTYLE CHOICE & OBESITY
BMI = weight (kg)/height2 (m)
Bray & Popkin Am J Clin Nutr 68:1157, 1998.
Carbohydrates: sweet
Minerals: salty
Protein: amino acid or umami
Alkaloids
Toxins
*Pharmaceuticals
*Ph
ti l
bitter
spoiled/rancid food: sour
Atropa belladonna
deadly nightshade
• Carbohydrates: sweet
• Minerals:
e a s sa
salty
y
• Protein: amino acid or umami
• Fat Taste ?
Fat: 9 kcal/gm
Protein/CHO: 4 kcal/gm
…most animals exhibit a preference for dietary fat
or
…including humans
times have changed,
our genes have not
Thrifty Gene Hypothesis:
Natural selection favored the survival of
those individuals who could store as many
calories as possible, then burn them as
slowly as possible [JV Neel, 1962]
Can fats activate the taste system?
May I h
M
have my own project?
j t?
May I have my own project?
May I have my own project?
Mayy I have myy own p
project?
j
May I have my own project?
May I have my own project?
Go put
fatty acids
on a taste
cell!!!
W.
W Todd Monroe
Science 244: 1176, 1989
Science 244: 1174, 1989
Todd’s first experiment
AJP 272: C1203, 1997
Æ fat has a “taste”
since 1997 Æ >1000 articles related to fat & taste
…a long way in our understanding of fat taste
Dr. Dane Hansen
Bhavik Shah
Cherry Liu
Tian Yu
Han Xu
Arian Baquero
Hala Hadawar
gene
PATHWAY TO SUCCESS
applies to any nutrition-related disorder
molecule
protein
cell
tissue/organ
b h i
behavior
treatment
me
limit carbohydrates (especially processed sugars)
Both South Beach and Atkins diets restrict
y
-- carbs, as diet dilettantes
carbohydrates
like to say. True, "good carbs" are allowed.
But South Beach dieters must say goodbye
to potatoes, fruit, bread, cereal, rice, pasta,
beets carrots,
beets,
carrots and corn for the first two
weeks. After that, most of these foods
remain strongly discouraged.
lost weight Æ went off diet Æ sweet taste altered
does our taste system reflect
our nutritional experience?
Dietary Preference in OM & S5B Rats
S5B
O-M
Food Inta
F
ake (g/da
ay)
8
**
S5B/Pl
6
4
**
2
0
protein
carbohydrate
fat
** p<0.001 compared w/ O-M
Redrawn from Okada et al. Am. J. Physiol 262:R1111, 1992
O-M
The Principle of Negative Feedback
Negative Feedback & Food Intake
activation of pleasure
p
or reward centers
senssory pro
operties
(taste
e)
+
set point”
point
“set
-
+
food intake
What can we learn
from animal models ?
S5B
O-M
identified & characterized fat receptor
lean rat – very responsive to fat
strong
obese rat – not as responsive to fat
weak
eats less fat
w
weak
sttrong
fat intake
fat intake
eats more fat
“does our taste system reflect
our nutritional experience?”
siblings
60 days
207 gm
368 gm
60 days
activation of pleasure or
reward centers
sensory properties
(taste)
+
“set p
point”
-
+
food intake
measure
fat receptor changes
is less responsive to fat
(like obesity-prone)
obesity prone)
ingests more fat
“a vicious cycle !?!”
put on a diet
return to low fat
(normal) diet (60 d)
parallels with humans…
• is this why dieting is so
prone to failure?
return to low fat
(normal) diet (120 d)
little/no weight
g loss
over ate the low fat diet
• is our sensory (taste)
system working against us?
slight recovery of original
fat responsiveness
Is there hope in the fight against obesity ?
education/outreach (to children) Æ
exercise;
food intake
The Surgeon General’s Call to Action to Prevent and Decrease Overweight and Obesity 2001
Is there hope in the fight against obesity ?
pharmacological approaches to reduce appetite (“magic bullet”)
a develop new targets (we have several)
b develop new ways to deliver old drugs
Nanomedicine
genes
pharmaceuticals
decrease
appetite
food intake
‘targeting proteins’
(antibodies, lectins…)
Rx
nanoparticle
enteroendocrine cells
loaded with nanoparticles
100 nm
Is there hope in the fight against obesity ?
nothing can do this!
energy balance =
food intake
energy
gy expenditure
p
Is there hope in the fight against obesity ?
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