Transcript Insulin Hypo

The Insulin Hypothesis
Primer on Regulation of Body Fat
 Biological factors regulate amount of fat in our bodies
 Modified by genetics
 Diets can affect this process
Carbohydrate Metabolism
 As carbs are digested, they are sent to bloodstream as glucose
 Insulin is released to help cells use glucose
 Cells in body burn some glucose immediately as fuel; store
some for later use
 Insulin stays high as long as carbs are available
Fat Metabolism:
 Occurs when insulin levels are low
 Fats burned for fuel after carbs are broken down
 broken down into fatty acids, which can be used as fuel
 Can flow in and out of cells
 If insulin is high: fat is stored as trigylcerides
 Composed of 3 fatty acids
 Too large to leave cells
Implications
 When insulin levels go up, we store fat; when they go down, we
mobilize fat and use it for fuel.
 Suggests that anything that makes us secrete more insulin will
extend periods during which we store fat and shorten the
periods we burn it
Results
 Obesity
 Hunger
 Can’t use carbohydrates stored in liver and muscle for fuel
 Vicious cycle:
 bodies getting bigger, so we need more fuel
 Energy demands increase, as does appetite
Why I Get Fat and You Don’t
 We all secrete insulin, yet
we don’t all gain weight
 Insulin effects depend on
genetics and other
individual differences
 Insulin determines how
fuels are “partitioned”
around the body
Calories into storage or energy
“less energy for physical
activity”
“impulse to be physically
active”
What determines which way needle points?
 1. How much insulin we secrete in response to food
 Given same food, some release more insulin
 Influenced by genetics
 Influenced by diet over years
 Influenced by pre-natal factors
 2. How sensitive our cells are to insulin
 How quickly “Insulin resistance” develops
 Influenced by genetics
 Influenced by diet over years
 Influenced by pre-natal factors
 3. How individual cells respond to insulin
 Muscle vs fat cells
 Changes with age and diet
 Influenced by activity
 Influenced by genetics
Prenatal Factors
 Mother’s weight and diet
 High glucose in mother’s blood results in higher blood glucose in
fetus
 Fetus responds by developing more insulin-secreting cells
 -baby born with more fat
 Has tendency to oversecrete insulin, develop insulin-resistance
What we can do
 Genetic predisposition is set off by carbohydrates we eat
 Not all foods that contain carbohydrates are equally
fattening- worst are those that have greatest effect on blood
sugar
 Concentrated sources
 Easily digested
 Refined flour, liquids, starches
 Eat fewer carbohydrates
 Improve the quality carbs eaten
 less refined (their glycemic index is low or at least lower)
 come with a lot of fiber attached (green leafy vegetables)
 Eat less sugars
 both sucrose and high fructose corn syrup.
Easier Said than Done
Are Sugary Foods Addicting?
Activate Reward Circuit
Release Dopamine
Qualify on Yale Food Addiction Scale
 I find when I start eating certain foods, I end up eating more than planned
 I find myself continuing to consume certain foods even if I am no longer hungry
 I eat to the point where I feel physically ill
 Not eating certain types of food or cutting down on certain types of food is
something I worry about
 I find that when certain foods are not available, I will go out of my way to obtain
them. For example, I will drive to the store to purchase certain foods even
though I have other options available to me at home.
 There have been times when I consumed certain foods so often or in such large
quantities that I started to eat food instead of working, spending time with my
family or friends, or engaging in other important activities or recreational
activities I enjoy.
 There have been times when I consumed certain foods so often or
in such large quantities that I spent time dealing with negative
feelings from overeating instead of working, spending time with
my family or friends, or engaging in other important activities or
recreational activities I enjoy.
 There have been times when I avoided professional or social
situations where certain foods were available, because I was afraid
I would overeat.
 I have had withdrawal symptoms such as agitation, anxiety, or
other physical symptoms when I cut down or stopped eating
certain foods. (Please do NOT include withdrawal symptoms
caused by cutting down on caffeinated beverages such as soda pop,
coffee, tea, energy drinks, etc.)
Sugar and Addiction
Hoebel (2008) Study: Sugar Binging in
Rats
 Rats deprived of food for 4 hours
 Given access to chow and sugar-water
 Binge on sugar solution
 Release dopamine in reward center
Become “addicted” to sugar
 After one month: fewer dopamine receptors
 Same changes seen in cocaine addiction
 Withdrawal symptoms when sugar solution taken away:
 Anxiety
 Teeth chattering
 Decreased dopamine/endorphin levels
 When sugar is re-introduced, worked harder to get solution
 Consume more than before deprivation
 Self-administered more alcohol than usual after sugar cut-off
Heatherton (2012): activation of reward
circuit
Nucleus Accumbens Activity predicts weight gain
Is Fructose Different than Regular
Sugar?
Most Lipogenic
 Has no immediate effect on insulin, unlike glucose
 Metabolized directly by liver
 Turned directly into fat
 Causes muscle tissue to become resistant to insulin
1. HFCS leads to Greater Weight Gain
 Hoebel (2010)
 Expt 1: rats given solution
sweetened with sucrose or
HFCS
 Same calories, but HFCS
rats gained more weight
 Expt 2: monitored weight, triglycerides, body fat in rats with
access to HFCS over 6 months
 Weight gain
 Increased triglycerides
 Fat deposits in abdomen
2. Bypasses Brain Satiety Circuits
From: Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite
and Reward Pathways
JAMA. 2013;309(1):63-70. doi:10.1001/jama.2012.116975
Figure Legend:
A, Functional connectivity analysis for glucose ingestion at baseline, with bilateral hypothalamus as the seed region. Hypothalamus
response to glucose ingestion was functionally connected to the caudate, putamen, and thalamus response. B, Functional
connectivity analysis for fructose ingestion at baseline, with bilateral hypothalamus as the seed region. Hypothalamus response to
fructose ingestion was functionally connected to the thalamus response. The images represent paired t tests for postdrink vs
baseline for 20 participants. Yellow and red regions
identify
areasAmerican
in the brain
with magnetic resonance imaging signal responses
Copyright
© 2012
Medical
Date
of download:
correlated
with the5/1/2013
hypothalamic response. Significance
threshold
set
P
<
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Association. All rights reserved.2-sided, family-wise error whole-brain corrected.
Montreal Neurological Institute (MNI) coordinates were used to define brain regions.
Glucose vs. Fructose
Table sugar (Sucrose): 50 % glucose and 50 & fructose
molecules bound together.
 HFCS: 45 % glucose to 55 % fructose.
 Hoebel HFCS Study: Sucrose and high-fructose have different
effects on body weight over time.
 Current Study: different effects on Brain?
 Subjects given drink sweetened with pure glucose or pure
fructose
 blinded, double-cross-over design
 Measured: blood flow in hypothalamus and other appetite
and reward regions, after ingestion
 Do they have different effects on Brain?
Results
 Glucose:
 Blood flow and activity in brain areas controlling appetite,
emotion and reward decreased
 participants reported greater feelings of fullness.
 Fructose:
 brain appetite and reward areas continued to stay active
 participants did not report feeling full.
Implications
 Fructose doesn’t “satisfy”
 Seems to bypass brain regulatory processes
 Removed from blood by liver- little reaches brain
 doesn’t raise insulin, but converted directly to fat in liver
 Response from Food Industry?
 new marketing campaigns: calorie counts
 Response from Lawmakers?
 New Labels
 Calorie Counts
Will it work?
 “The evidence on whether such labels have done much to reduce
calorie consumption is mixed, but there is no doubt that many people
do make different choices when they realize how many calories a
favorite food contains.”
• NYTimes Op-Ed, Nov 24, 2014