1 The Insulin Hypothesis
2 Primer on Regulation of Body FatBiological factors regulate amount of fat in our bodies Modified by genetics Diets can affect this process
3 Carbohydrate MetabolismAs 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
4 Fat Metabolism: Occurs when insulin levels are lowFats 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
5 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
6 Results Obesity Hunger Vicious cycle: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
7 Why I Get Fat and You Don’tWe 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
8 Calories into storage or energy“less energy for physical activity” “impulse to be physically active”
9 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
10 2. How sensitive our cells are to insulinHow quickly “Insulin resistance” develops Influenced by genetics Influenced by diet over years Influenced by pre-natal factors
11 3. How individual cells respond to insulinMuscle vs fat cells Changes with age and diet Influenced by activity Influenced by genetics
12 Prenatal Factors Mother’s weight and dietHigh 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
13 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
14 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.
15 Easier Said than Done Most fattening foods are those we crave
16 Are Sugary Foods Addicting?
17 Activate Reward Circuit
18 Release Dopamine
19 Qualify on Yale Food Addiction ScaleI 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.
20 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.)
21 Sugar and Addiction
22 Hoebel (2008) Study: Sugar Binging in RatsRats deprived of food for 4 hours Given access to chow and sugar-water Binge on sugar solution Release dopamine in reward center
23 Become “addicted” to sugarAfter 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
24 When sugar is re-introduced, worked harder to get solutionConsume more than before deprivation Self-administered more alcohol than usual after sugar cut-off
25 Heatherton (2012): activation of reward circuit
26 Nucleus Accumbens Activity predicts weight gain
27 Is Fructose Different than Regular Sugar?
28 Most Lipogenic Has no immediate effect on insulin, unlike glucoseMetabolized directly by liver Turned directly into fat Causes muscle tissue to become resistant to insulin
29 1. HFCS leads to Greater Weight GainHoebel (2010) Expt 1: rats given solution sweetened with sucrose or HFCS Same calories, but HFCS rats gained more weight
30 Expt 2: monitored weight, triglycerides, body fat in rats with access to HFCS over 6 monthsWeight gain Increased triglycerides Fat deposits in abdomen
31 2. Bypasses Brain Satiety Circuits
32 Copyright © 2012 American Medical Association. All rights reserved.From: Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite and Reward Pathways JAMA. 2013;309(1): doi: /jama 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 areas in the brain with magnetic resonance imaging signal responses correlated with the hypothalamic response. Significance threshold set P < .05, 2-sided, family-wise error whole-brain corrected. Montreal Neurological Institute (MNI) coordinates were used to define brain regions. Date of download: 5/1/2013 Copyright © 2012 American Medical Association. All rights reserved.
33 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?
34 Subjects given drink sweetened with pure glucose or pure fructoseblinded, double-cross-over design Measured: blood flow in hypothalamus and other appetite and reward regions, after ingestion Do they have different effects on Brain? Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite and Reward Pathways; JAMA (2013)
35 Results Glucose: Fructose: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.
36 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
37 Response from Food Industry?new marketing campaigns: calorie counts Response from Lawmakers? New Labels Calorie Counts
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39 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
40 http://www. nytimes. com/2009/10/06/nyregion/06calories. html
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