Obesity

Question 1

How much cancer is attributable to obesity

Answer 1

1 in 6 cases. Most commonly Breast, prostate, colon

Question 2

The fat 4, or not?

Answer 2

USA, Canada, UK and Germany used to be. But in actual fact other races are experiencing much more increase in obesity (eg China).

Question 3

Describe obesity as a chronic disease

Answer 3

Chronic = lifelong Treatment required. Similar to hypertension, diabetes, asthma. Treatment controls, does not cure, disease. No short-term solutions: need for lifelong management. Disease recurs after treatment is withdrawn, NOT due to patient or treatment failure

Question 4

List some complications of obesity (don’t worry about this too much)

Answer 4

Picture

Question 5

What causes osteoarthritis in obesity?

Answer 5

It’s actually not mechanical due to the weight. Obesity causes inflammation, which causes the arthritis.

Question 6

Psychological consequences of obesity

Answer 6

Bullying; School avoidance; Social isolation; Compromised peer relationships; Depression (48% mod-severely obese youth); Anxiety (35%); Suicidal ideation, gestures, attempts; Poor self-esteem; Poor quality of life; Binge eating, disordered eating, eating disorders

Question 7

Calculating BMI and categories.

Answer 7

kg/m^2. (wt/ht^2). Table

Question 8

BMI in children

Answer 8

A BMI above the 85th percentile is overweight. A BMI above the 95th percentile is obese. Remember that the BMI percentile depends on age AND gender.

Question 9

Subcutaneous vs visceral fat

Answer 9

Sub is less “bad”, less metabolically active. Measure waist circumference, correlates with visceral fat. 94/80 cm (M/F) is overweight and increased risk, 102/88 cm is obese/substatial risk

Question 10

Genetics and environment

Answer 10

Genetic predisposition + environmental factors lead to structural factors (lifestyle environment) and individual behaviour

Question 11

Evolution and obesity

Answer 11

The ability to rapidly store fat was an advantage to survive. (thrifty gene hypothesis)

Question 12

Basal metabolic rate and resting metabolic rate

Answer 12

Basal metabolic rate: Na/K pumps! (2/3 of our calories). Resting metabolic rate: Na/K pumps and blinking, breathing, etc (3/4 calories).

Question 13

Reporting issues and obesity

Answer 13

Many people underestimate how many calories they eat and overestimate how much they exercise.

Question 14

What nutrient is most responsible for obesity?

Answer 14

We are eating more CHO now than ever. Used to eat more fat but then people started posting “low fat” food. Fat stimulates satiety. CHO increases insulin, which increases uptake and fat production.

Question 15

Issues with glycemic index

Answer 15

Get absorbed super fast. Counter intuitive. Carrots are high! White bread is lower than whole wheat!

Question 16

Overlapping issues in obesity (general)

Answer 16

Psych, media, economic, medical, social, medical, social, infrastructure, activity, development, biological, food. Kind of complicated.

Question 17

Genetic variables and obesity

Answer 17

Response to nutrients (fat, carbohydrate), Response to exercise, Basal metabolic rate / mitochondrial factors, Epigenetic changes (results of stress), Proportion of brown adipose tissue

Question 18

What is the Leptin hormone?

Answer 18

Produced by fat cells (adipocytes). Classically thought to signal “fatness”, Actually probably signals “thinness”. Obese patients have increased levels, implies receptor or post-receptor defect - resistance to leptin.

Question 19

What does leptin do?

Answer 19

As leptin rises, signals decreased food seeking and increased thermogenesis. Upregulates anorexins: POMC (origin of ACTH) and CART. Downregulates orexins: AGRP and neuropeptide Y

Question 20

What is neuropeptide Y?

Answer 20

Hormone produced in gut. Most potent stimulator of feeding (orexin).

Question 21

Why doesn’t treatment with leptin or neuropeptide knockouts work well?

Answer 21

Many redundant backup mechanisms to stimulate eating behaviour etc etc.

Question 22

What is POMC?

Answer 22

Pro-opiomelanocortin. Pro-hormone of ACTH, MSH a, ß and gamma. a and ß-MSH in CNS bind to MC4 receptor and inhibit feeding; Agouti-related peptide blocks MC4

Question 23

What does serotonin do?

Answer 23

Hormone. 14 different receptors in brain. Some increase appetite (we generally have more of these receptors), some decrease. Serotonin stimulation may help binge eating behaviours. Chocolate has serotonin. Some receptors in rest of body, different effects on fat storage etc.

Question 24

Cholecystokinin, ghrelin, and endocannabinoids

Answer 24

Cholecystokinin: stimulate gall bladder to secrete bile; CCK-1 receptor stimulation decreases appetite, CCK-2 stimulation leads to psychosis. Ghrelin: produced by empty stomach, stimulates NPY and AGRP. Endocannabinoids: 2-arachidonoyl glycerol and anandamine, Inhibitor designed to block marijuana effect - Blocks appetite (“munchies”), 5 clinical trials with antagonist (rimonabant)

Question 25

Brown adipose tissue

Answer 25

Common in animals. Metabolic rate: production of ATP. Thermogenesis: production of heat. Human equivalent? β3 stimulation activates PPARγ co-activator which leads to uncoupling protein synthesis. Uncoupling proteins 1-5, 1 and 2, maybe more, in humans. Uncoupling proteins in mitochondria of BAT: Unlink e- transport from ATP production, Energy dissipated as heat. Drugs that do this are CN, CO, and metformin.

Question 26

Monogenic obesity

Answer 26

Leptin deficiency (very rare), give leptin. Melaonoctin-4-receptor mutation: 4-6% of obese kids; early onset severe obesity, food seeking, hyperinsulinemia. Treatment is behavioral (caloric intake expenditure)

Question 27

Syndromic obesity

Answer 27

Genetic or chromosomal defects. Two most common obesity syndromes: Prader-Willi Syndrome and Albright’s Hereditary Osteodystrophy. Treatment: behavioral (restrict food).

Question 28

Endocrine disorders and obesity

Answer 28

Not as common. Usually Hypothyroidism (low free T4), Cushing’s Disease (high cortisol), Growth hormone deficiency, Hypopituitarism (CNS injury)

Question 29

Neuromuscular defects and obesity

Answer 29

Congenital or acquired, Inability to move: Loss of muscle mass , Decreased energy expenditure, Requires dietary treatment

Question 30

Medications and obesity

Answer 30

Glucocorticoids; Newer antipsychotics or antidepressants (Risperidone, Olanzapine, Clozapine, Paroxetine (Paxil®), Amitryptaline (Elavil®)); Antiepileptics: Valproate, Carbemazepine

Question 31

Benefits of weight loss

Answer 31

For each 1 kg loss, life expectancy increases by 3-4 months. Reducing the BMI to <28 will decrease cardiovascular mortality by 50% (77% if hypertensive). Even people who try but don’t lose weight are at lower risk.

Question 32

What is success in weight management?

Answer 32

Losing weight (how much) and how we maintain the loss

Question 33

Current approaches in weight management

Answer 33

Dietary intervention, Increased physical activity, Behavioral modification, Psychological and social support, Pharmacotherapy, Surgical intervention

Question 34

Comments on dietary intervention

Answer 34

Meal replacement is good for underreporters. But generally most diets etc will reduce weight modestly with some regain after (metabolism can overcompensate).

Question 35

Comments on exercise

Answer 35

Exercise doesn’t necessarily burn tons, but dramatically increases metabolic rate and remains elevated for 24-72h afterwards (excess post-exercise O2 consumption). Depends on intensity of exercise. Long-term exercise may elevate resting metabolic rate (RMR). Other benefits: Improved physical fitness, Facilitates greater more intense daily activities, Acts on brain like fat intake, Produces rates of fat oxidation similar to fat intake, Beneficial effects on lipid mobilization and oxidation, Biochemical/morphologic changes in muscle fiber

Question 36

Who is a candidate for pharmacological treatment? What do they target?

Answer 36

BMI >27 and 1 other CV factor, or BMI >30. Reduce Energy intake (lower hunger, more satiety, less absorption) and increase energy expenditure (increase metabolic rate)

Question 37

Orlistat

Answer 37

Inhibits intestinal lipases, decreases fat absorption by about 30%, leads to a 5-10% weight loss in obese subjects

Question 38

Sibutramine

Answer 38

serotonin and NE reuptake inhibitor; acts by decreasing appetite and by increasing activity of β3 receptors in BAT (leading to an increase in ‘metabolism’); may directly increase insulin sensitivity

Question 39

Antiobesity drugs in development

Answer 39

Cannabinoid receptor blocker (rimonabant), Ciliary neurotrophic factor, Lipase inhibition, Adrenergic β3 receptor agonists, Vegetable-based natural appetite suppressants

Question 40

Bariatric surgery procedures

Answer 40

Stapling or partial gastrectomy - old, less effective (stomach stretches). Gastric bypass (roux-en-Y): stomach still there but food doesn’t enter there. Good effects on people at risk (recover the medical costs within 2 years).

Question 41

Indications for bariatric surgery

Answer 41

BMI > 40, or BMI > 35 and co-morbidities or significant risk factors. 25% adverse events (bloating, abdominal pain)

Question 42

Benefits of bariatric surgery

Answer 42

Significant of decreased all cause mortality, CV disease, cancer, diabetes (huge)

Question 43

Summary of obesity

Answer 43

Obesity is a chronic disease, Risk factor for many other diseases, Manageable with lifestyle modifications and pharmacotherapy (in appropriate patients), Modest weight losses (5% to 10%) provide significant health benefits, Realistic expectations must be established