Obesity

Question 1

What Factors Contribute to the development of obesity?

• G______/E_______
• B_______ (inactivity)
• En_______
• Ps_______ (binge eating disorders)
• M_______ ( insulin, steroids)
• E_______ factors
• M_______ conditions

Answer 1

• Genetics/Epigenetics
• Behavioral
• Endocrine
• Psychological
• Medications
• Environmental
• Medical Conditions

Question 2

What factors (in terms of gender, race/ethnicity, education, geographic region) are associated with a greater rise in obesity in the years leading up to 2016?

Answer 2

No biological difference, race and ethnic differences reflect social and cultural issues

Question 3

What conditions are among some of the most common obesity-related complications?

• D_______
• C______
• Ost______
• Nonalcoholic (1)
• _ _ _

Answer 3

• Diabetes Type 2
• Cancer
• Osteoarthritis
• Nonalcoholic fatty liver disease
• OSA

Question 4

What is BMI? How is it Calculated?

Obesity = BMI of?

Answer 4

Body Mass Index = weight (kg)/height (meters2)

Used to screen for obesity and categorize pts risk for obesity related disorders

BMI > 30

Question 5

Advantages and Disadvantages of using BMI to assess obesity risk?

Advantages

• High correlation to?
• Minimal _____
• In______
• Non_______

Limitations

• Surrogate measure so can result in (2)
• Ignores ______ variability

Answer 5

• % total body fat
• Minimal time
• Inexpensive
• Noninvasive
• Overestimation (high lvls of muscle), Underestimation (low lvls of muscle)
• ethnic variability (certain ethnic groups have increased risk of weight related comorbidities at lower BMI’s than caucasians -> need to use adjusted BMI cutoffs)

Question 6

What type of body fat distribution is associated with the highest risk for metabolic disease? How can this be assessed in a non-invasive way?

Answer 6

• Subcutaneous fat tends to be metabolically benign
• Excess visceral fat = directly tied to increased risk of type II DM, HTN, Cardiovascular disease, metabolic diseases
• Waist circumference is indirect way to assess amount of visceral fat (especially waist:hip ratio around hip mostly subcutaneous fat)

Question 7

How did the intermittent and unreliable access to food in early human history shape the general direction of our system for maintaining energy balance and energy stores?

Answer 7

• Food was scarce with moments of starvation. In order to survive, we developed an internal alert system. Human genes have evolved into the development of a complex appetite and energy regulated system…
  
  • Storing fat as energy for later
• We’ve developed ways to keep food nearby from animal domestication, preserving foods (canned food),

Question 8

What brain regions control appetite and energy expenditure? These brain regions depend on signals from which body structures to modulate appetite and energy expenditure?

Answer 8

The control centers in the brain (prefrontal cortex/ cortex/ hypothalamus/ amygdala/ nucleus accumbens/ brainstem) send signals to and from peripheral organs (adipose tissue and gut)

Question 9

Which brain regions involved in controlling appetite and energy expenditure are also involved in our pleasure/reward system? What neurotransmitter is critical for our reward system?

Answer 9

• Amygdala/ nucleaus accumbens/ hypothalamus are the reward system
• Explains why highly palpable foods are able to override homeostatic signals which would normally tell us to end a meal
• DOPAMINE- is the neurotransmitter for desire….dopamine reminds you of a past pleasure ex: food, sex, etc. Related to emotional eating.

Question 10

What is the hypothesized connection between the number of dopamine receptors, intensity of the pleasure/reward response, tendency for overeating, and risk for obesity?

Answer 10

• Some patients with obesity have less dopamine in dorsal striatum than lean counterparts
• Taq1A regulatory gene is associated with increased likelihood of obesity
• Those who lack this gene have a normal amount of dopamine receptors and STOP eating
• Those who have this gene have less dopamine receptors and continue eating to compensate for hypofunctioning dopamine reward system

Question 11

What hormonal changes associated with insufficient sleep can cause increased appetite and increased risk for obesity?

Answer 11

Question 12

What is an Obesogenic Environment? What aspects of modern life and society contribute or promote this kind of environment?

Answer 12

• Obesogenic Environment: environmental changes that promote behaviors which favor weight gain
• Decreased energy expenditure
  
  • More sedentary occupations due to decreased automation
  • Workplace layout discourages physical activity
  • Home appliances
  • Play time for children has been shortened
  • Increased sedentary time watching tv, video games etc
  • Dangerous neighborhoods
• Increased energy intake
  
  • Increased availability and advertising of calorie dense foods
  • Increased snacking
  • Consumption of sugar sweetened beverages.
  • Increased portion sizes
  • Decreased sleep time
  • Food insecurity- cheaper calorie dense foods, overeating when food is available.
  • Mindless distracted eating- we get distracted from sensory input
  • Food insecurity - cheaper, calorie dense foods, or overeating when more food available

Question 13

What is a “Food Desert”? Who is most likely to be affected by these kinds of locations?

Answer 13

• *Contributes to higher rates of obesity in impoverished areas
• Effects elderly or fixed/low income individuals

Question 14

Based on the many factors that contribute to obesity, what are some key components that can/should be included in a personalized treatment plan?

Answer 14

Question 15

What type of screenings and specialists may be needed for a personalized treatment plan to be effective?

Answer 15

Question 16

Key Points

Complex neuroendocrine system

• Controls app______ and _____ expenditure
• Overlaps with _____ system

Environmental and behavioral change

• Promote _______ energy intake
• Caused ______ energy expenditure

Answer 16

• appetite, energy
• reward
• increased energy intake
• decreased energy expenditure

Question 17

What trend was observed in the 1976 study of body shape (and height) among monozygotic (aka “identical”) vs. dizygotic (aka “fraternal”) twins?

Answer 17

• Confirmed importance in genetics in determining body weight
• Discovered monozygotic twins had highly concordant levels of body fat and height. Dizygotic twins had significant differences.
  
  • Therefore, genetics does play a role in height and body fat

Question 18

A variety of genes have been found to directly affect 7 parameters related to weight and adiposity. Identify and define those 7 parameters.

1. B_____weight
2. _____ to _____ ratio or waist c______ adjusted for ____
3. V_______ adiposity
4. _____ to _____ ratio or _____ circumference
5. Extreme ob_____
6. B _ _ relatd
7. Body F___

• ______ centers around a group of genes
• (1) genes affect 4/7 parameters. Highly related to _____

Answer 18

1. Birthweight
2. Waist to hip ratio, waist circumference adjusted for BMI
3. Visceral adiposity
4. Waist to hip ratio or waist circumference
5. Extreme obesity
6. BMI related
7. Body Fat

• Overlapping
• FTO genes, high regulated BMI

Question 19

While genes have been identified as clearly playing a role in several parameters related to weight and adiposity (such as the FTO gene), studies have demonstrated that only 1% of changes in BMI can be directly attributed to differences in the FTO gene. How does this information help us understand the development of obesity in some people?

• Shows that this gene alone does what to explain differences in body weight?
• It’s more complicated than just the ______ (FTO) - Obesity is the _______

Answer 19

• Genes alone don’t come close to explaining differences in body weight
• more complicated than just the genotype, obesity is the phenotype

Question 20

Explain the findings of the 1990 and 1994 study comparing weight gain and loss among monozygotic twins. What do these findings suggest about the strength of the factors that influence the response an individual’s body may have to overeating or dieting?

• Both positive energy balance (overfeeding) and negative energy balance (increased exercise) causes_______ changes in body weight
  
  • Twin A gained 7kg and twin B gained 8kg, Second graph twin A lost 8 and twin B lost 7.5kg
  • Demonstrates a body’s response to energy intake is from _______ and not just _______
    
    • Bc twins ______ genes they react ______ to under or overeating HOWEVER different twin pairs react _______
    • Diff ppl’s bodies respond diff to diff _________ - similar genes, diff env________ (ex Pima ______)

Answer 20

• similar
  
  • GENETICS not just BEHAVIOR
    
    • twins share genes they react similarly, diff twin pairs react differently
    • environments - diff genes, diff environments (Pima indians)

Question 21

What is Epigenetics?

How does epigenetics help explain how environment can affect gene expression?

What environmental factors are known to cause epigenetic changes?

Answer 21

Epigenetics = environment can change gene expression without changing genetic code. Can be passed down to offspring

Ex) Addition of methyl group, preventing binding of transcription factors, presenting expression.

• Effects if histone tail is exposed vs. nonexposed (accessible)

Epigenetic changes can increase risk of obesity for multiple generations

Question 22

For babies born “small for gestational age” SGA, it is believed that they experience malnutrition-induced-epigenetic changes in utero that increase the expression of metabolic-efficiency genes (i.e. able to more easily store fat from fewer calories and better at conserving energy.) What observed differences among 10 year olds born SGA vs. AGA lead to this SGA-metabolic-efficiency theory?

Answer 22

• AT 4 years, children born LGA are born with larger and average for gestational age, the LGA are born with higher BMIs
• At 10 years, Found females and males born SMALLER than GA, are also found to be obese. Adapt to an intrauterine environment where there was little nutrition, so their body learns to hold onto calories.
• Also high caloric intake for catch up growth

Question 23

What trend did studies find between percentage of visceral fat and birth weight? How is this trend similar with adult onset diabetes?

Answer 23

Smaller and larger weight are born with more visceral fat.

Also higher for DM for smaller and larger GA vs normal GA.

Question 24

Key Points

• Multiple g_______ contributions to weight
• Genes play a role in ______ balance
• Genes determine the body’s response to states of energy _____ or _______
• Genes AND ______ determine body weight
• E_______ influences on genes begin ____ in life
• Environment causes ______ changes in gene expression

Answer 24

• genetic
• energy
• excess or depletion
• environment
• Environmental, early
• epigenetic

Question 25

Clinical Implications ## Footnote * Avoid ass\_\_\_\_\_\_\_ * Thorough ______ taking, including family and social history * Let the _____ tell you about contributors to excess weight, their dietary ______ and physical _____ levels * B\_\_\_\_\_ the patient * Each patient is an individual, interventions need to be p\_\_\_\_\_\_\_\_

Answer 25

* assumptions * history * patient tell you, intake, physical activity * Believe * personalized

Question 26

What kind of specific improvements in health have been observed with just a **5-10%** decrease in body weight?

Answer 26

**Hgb A1C** **Blood Pressure** **Other cardiovascular risk factors**

Question 27

True or False – intensive weight loss interventions (compared to no intervention), while successful in the short term, do not result in long term improvement of health due to a high rate of weight regain. Explain your answer.

Answer 27

**False**: although weight did increase in years 1-5, in 10 yrs, despite weight regain, 6% weight loss still enough to maintain improvement in cardiovascular risk factors

Question 28

What percentage, on average, of those losing 10% or more of their body weight managed to maintain the loss for at least 2 years?

Answer 28

Most optomistic data suggest that 60% of those cannot maintain 10% weight loss for more than 2 years -\> **Answer is ~40%** However statistic is inaccurate bc data only from ppl in commercial weight loss programs

Question 29

What is adaptive thermogenesis (part of the counter-regulatory response to weight loss) and what does it have to do with weight regain?

Answer 29

* **Definition: Changes in energy expenditure, autonomic nervous system function and neuroendocrine function in subjects maintaining a reduced body weight (Effects of 10% reduced weight maintenance) - a counterregulatory system** * From premodern times when food intake was unpredictable Body developed mechanisms to maintain higher weight and prevent starvation * Resting and Non-resting MR decreases (to burn same amount of calories as someone who hasn't lost weight, need to work 2x harder) dt skeletal muscle efficiency increases * SNS decreased, gonadotropin, and circulating leptin decreases * These changes never go away

Question 30

What are some of the features of adaptive thermogenesis with regard to energy expenditure and food consumption? ## Footnote * Metabolic rate ______ to preserve energy * Reduces daily ______ burn by 15% * Muscles become 20% more \_\_\_\_\_\_ * ______ increases and ______ decreases to encourage food seeking behavior and consumption of food * Changes in ______ and _______ changes that also promote weight gain

Answer 30

* **Metabolic rate slows** * **caloric burn reduces** * **Muscle more efficient** * **Appetite increases, Satiety decreases** * **Autonomic, Neuroendocrine**

Question 31

Describe the following hormones with regard to their site of production and actions in the body ## Footnote * **Ghrelin** * **Source =** * **Normal Function =** * **Alteration =** * **Peptide YY** * **​Source =** * **Normal Function =** * **Alteration =**

Answer 31

* Gastric fundus * Stimulate appetite, particularly high fat, high sugar foods * Levels increase during dieting and weight loss * Distal small intestine * Suppresses appetite * Levels decreased in obese persons

Question 32

Describe the changes in Ghrelin and peptide YY levels throughout the day in a person who has lost weight through lifestyle changes alone. What effect does this have on the individual? How long with these hormones remain altered after weight loss?

Answer 32

* Ghrelin: "hunger hormone" **increases** after weight loss * Peptide YY: "Satiety hormone" **decreases** after weight loss (delays gastric emptying, helps signal end of a meal, improves insulin sensitivity) * Hormonal and metabolic changes persist life long or as long as a person maintains a lower weight

Question 33

What drugs/drug classes are associated with weight gain?

Answer 33

Question 34

Among those whose weight loss was tracked by the National Weight Loss Registry, what percentage of individuals used both diet and exercise to lose weight? What behaviors were associated with successful maintenance of weight loss. * 89% used? * Behaviors * Following a (1) diet 1400-1800kcal/day * 60-90 min (1) * Daily \_\_\_\_\_\_\_ * Self _______ weight * Action _____ if weight increases a few pounds

Answer 34

* **both diet and physical activity** * **low calorie diet** * **moderate physical activity** * **daily breakfast** * **self monitor** * **plan**

Question 35

Which medications are approved by the FDA for long-term therapy for weight loss? What percentage of weight loss is associated with these medications? **(LLNPO)**

Answer 35

**On average, weight loss achieved on these medications is 10%, however some may not be candidates for or respond to some meds**

Question 36

How does the average weight loss success rate of bariatric surgery compare to that of anti-obesity medications or life style modification alone? What is the likely explanation for the difference?

Answer 36

* **15-35% weight loss at 5 yrs** * However this means that after 5 years, many ppl will gain the weight back -\> so need surgery + lifestyle modification combination to keep it off * All mechanisms are not known but probably due to anatomic and hormonal changes and not from sheer will pair * However is not a magic bullet and weight regain does occur although at a much lower rate than with lifestyle or medication interventions.

Question 37

Key Points ## Footnote * \_\_-\_\_% of weight loss -\> improved health * Weight loss and *especially* _______ is difficult * (1) response causes weight regain * Hormonal adaptations last how long? * Chronic _______ may promote weight gain/regain * M\_\_\_\_\_\_ of patients losing weight with lifestyle changes regain * Higher rates of weight loss/maintenance with m\_\_\_\_\_ * Highest rates of weight loss/maintenance with (1), likely due to associated ______ changes

Answer 37

* 5-10% * maintenance * Counter-regulatory * persist life long * medications * medication * bariatric surgery, hormonal

Question 38

Clinical Implications ## Footnote * Help patient set ______ goals * Avoid unrealistic e\_\_\_\_\_\_\_ which can sabotage patients * Focus on changes in \_\_\_\_\_\_ * Remind patients * of their _____ for wanting to lose weight * _____ amounts of weight loss can improve health * ______ are a normal part of weight management * Consider weight _____ potential of medications * C\_\_\_\_\_\_ patients for their efforts to improve health, weight loss, and weight maintenance efforts * Eliminate j\_\_\_\_\_\_ based on changes on the scale

Answer 38

* realistic * expectations * behavior * reasons * small * setbacks * gain * celebrate * judgements