What causes weight gain?

1. Theodore C. Friedman, M.D., Ph.D. (the Wiz) Professor of Medicine-UCLAChairman, Department of Internal MedicineCharles R. Drew UniversityDr. Friedman’s Endocrinology ClinicHow Pituitary Hormones Affect Weight and Sleep MAGIC Adult Convention Chicago, ILJuly 22, 2016

2. What causes weight gain? • More calories intake than calories expended. • Duh Dr. Friedman, that’s not why I came to Chicago.

3. What causes weight gain? • The 3 Ss • Sleep Deprivation • Stress • Social Jet Lag • Lack of food-time restriction

4. What causes weight gain? • Weight balance is a complex process that depends on: • Hormones • Other medical conditions • Sleep • Stress • Mood • Motivation to stick to life style changes

5. Stress • Stress definitely have negative effects on health, and it seems like everybody is stressed. • Stress is defined as anything that is a threat either "real" or "imaginary" to homeostasis. • Homeostasis is your hormonal balance. • A real stress would be seeing a tiger escaping from the zoo and about to eat you. • An imaginary stress would be giving a talk about a topic you are not familiar with. • Both of these stresses are harmful.

6. Stress • Several studies have shown that stress is correlated with weight gain • One of the main mechanisms is that stress activates the hypothalamic-pituitary-adrenal axis that gives a higher level of cortisol. • The high cortisol leads to weight gain predominantly in the abdominal area. • However, stress also causes increased food intake even when people are not necessarily hungry.

7. Stress • A study was done where they fed people until they were no longer hungry, then had them do a stressful task and then gave them a tray of snacks. • They ate more if they were stressed even though they were not hungry, so there is something about stress that leads to overeating, especially comfort foods. • Comfort foods are foods that your mother used to make for you and includes mashed potatoes and macaroni and cheese.

8. What hormones control weight? • High cortisol-high with stress and Cushing’s syndrome • Low thyroid hormones • Low GH-IGF1 • High Insulin • Low leptin • Low testosterone • Low estrogen • Low oxytocin

9. How does cortisol (and stress) lead to weight gain? • High cortisol leads to visceral (central obesity). • High night time cortisol may be more detrimental • Most studies suggests it increases appetite. • I’m not so sure as most of my Cushing’s patients don’t eat that much • May affect type of foods: “comfort foods”

10. How does cortisol lead to weight gain? • Cortisol stimulates lipoprotein lipase (LPL) and inhibit hormone sensitive lipase (HSL), enzymes involved in fat storage. • These enzymes are mainly in visceral fat which is why cortisol leads to weight gain there. • Cortisol and insulin leads to storage of triglycerides (TG) and decreased breakdown of fat. • Cortisol leads to larger fat cells (adipocytes). • GH, testosterone, and to a lesser extent, estradiol, act oppositely to the combination of cortisol and insulin by stimulating fat breakdown.

11. How does cortisol lead to weight gain? • Cortisol (from stress or Cushing’s syndrome) inhibits thyroid, growth hormone and reproductive axis, further leading to decrease abdominal fat breakdown. • Cortisol stimulates glucose production which leads to more fat. • Cortisol increases NPY a brain appetite hormone. • How does high night time cortisol lead to weight gain even for people that don’t eat at night? • Don’t know but when I put patients with Cushing’s syndrome on ketoconazole at night, they lose weight.

12. How does cortisol lead to weight gain? • Cortisol decreases muscle strength making it harder top exercise • High cortisol leads to fatigue by unknown mechanisms. • High cortisol leads to poor sleep, which leads to weight gain, probably by changing food preference to comfort foods, high fat and sugary foods. • Poor sleep leads to high cortisol • Stressed is desserts spelled backwards • Hard to avoid stress, better to deal with it better

13. How does insulin lead to weight gain? • Cortisol increases insulin • Insulin facilitates the conversion of energy into fat • Insulin stores fat for a “rainy day”-weight gain • When insulin levels drop, body starts to burn fat and weight loss occurs • Normally leptin tells your body to make less insulin, so you don’t store fat. In obesity and Cushing’s syndrome, leptin doesn’t turn off insulin, so you keep on converting energy to fat

14. How does insulin lead to weight gain? • High insulin blocks leptin so you feel hungry, even when full • In insulin resistance, which occurs in obesity, your insulin doesn’t bind to the receptor properly and you fail to sense that you are full. • You get more dopamine released when you eat, so you get more reward after eating comfort foods. • You become addicted to food. • High glycemic foods lead to a release in insulin • Eating high fiber foods prevents the release of insulin • Metformin can reduce insulin levels

15. How does leptin lead to weight gain? • Leptin is made in your fat cells. • The more fat cells, the higher your leptin • High leptin tells you not to eat any more, low leptin tells you to eat more • Most obese people are leptin resistant, so you still eat even if full • If leptin resistant, both starvation and reward signals occur, making it especially hard to lose weight.

16. So what do you do if you have high cortisol and are insulin and leptin resistant • Exercise-although it raises cortisol acutely, it lowers cortisol levels later in the day. • Exercise prevents insulin resistance and improves clearance of fat from the liver • Deal with or reduce stress • Carbs stimulate insulin release, so your better off on a low carb, low glycemic diet.

17. Thyroid hormone • Thyroid hormone please a crucial role in metabolism • Hypothyroid patients have slower metabolism. • They are also more tired, have fluid retention and have a harder time to exercise. • Their liver doesn’t work as well to metabolize glucose • Hypothyroid can lead to weight gain, but its usually modest. • Hashimoto’s hypothyroidism (autoimmune disease) with positive Tpo antibodies or patients who had a thyroidectomy usually have more weight gain • Patients with hyperthyroidism have increased appetite, so I do not recommend using thyroid hormone for weight loss in someone with normal thyroid tests.

18. Growth hormone • GH is made in the pituitary and goes to the liver to release IGF1. • GH itself can lead to diabetes and insulin resistance • But IGF-1 is the active hormone and increases metabolism • IGF-1 decreases fat stores and leads to increase muscle mass • In patients with normal IGF-1 levels who are not growth hormone deficient, GH has minimal effects on weight and increases the risk of cancer.

19. Growth hormone • In patients that are growth hormone deficient (confirmed by a growth hormone stimulation test), growth hormone treatment leads to: • Increased energy • Increased muscle mass • Better sleep • Decreased abdominal fat • Weight loss • Serovital (serovital.com) is a supplement of amino acids that stimulated GH. • Patients with low IGF-1 who are not growth hormone-deficient may benefit from serovital.

20. Testosterone • In both men and women with low testosterone, testosterone replacement increases muscle mass and decreases abdominal fat • Blocks some of the detrimental effects of cortisol on fat. • Not recommended in men and women with nromal testosterone

21. Estrogen • Weight gain is common in peri-menopausal and menopausal women. • Maybe related to worsening mood and poor sleep. • Low estrogen may lead to fat storage. • Estrogen replacement is often beneficial in peri-menopausal and menopausal women.

22. Poor Sleep • Low estrogen leading to poor sleep may lead to diabetes and obesity.

23. Oxytocin • Oxytocin is made by the posterior pituitary like AVP. • Only prominent pituitary hormone not tested or replaced • May have a role in bonding, intimacy, orgasm, GI issues, trust, generosity, pain and energy • 2015 Endocrine Society abstract showed oxytocin gave weight loss in men • Need to be studied more, but I am measuring it in a 24 hr urine assay and treated those with hypopituitarism and low urine oxytocin levels with some weight loss reported.

24. Poor sleep • Over the past 50 years, we went from sleeping about 8-1/2 hours a night to 7 hours or less. • This happened about the same time as the obesity epidemic has blossomed and now more people are staying up later using their electronics. • Studies have shown that people who sleep less than 7 hours a night have higher levels of cortisol and are more likely to be overweight and get diabetes than those who sleep at least 8 hours.

25. Poor sleep • In addition to sleep quantity, sleep quality is also important. • Therefore, a good night's sleep is essential for proper cortisol levels and to prevent weight gain. • There are apps that can track how many hours a night you sleep and how many times you wake up. • These apps can be quite helpful in determining your quality of sleep.

26. Social jet lag • Social jet lag is a term meaning that your circadian rhythm (body’s own clock) is different from what the real world expects from you (society’s social clock). • Some people are nighttime persons and some people are morning persons. • If a nighttime person had his choice, he might go to bed at 6 in the morning and sleep until 3 in the afternoon. • However, society forces him to go to bed around 10 or 11 at night and wake up around 6 in the morning to get to work at 8 in the morning.

27. Social jet lag • This is called social jet lag when there is a disconnect between the body's own circadian rhythm and what society imposes on the person. • Social jet lag seems also to raise cortisol levels and leads to obesity.

28. Social jet lag • When the person who is a night owl but goes to bed at a regular time during the week followed by the weekend, when he resumes his normal circadian rhythm and can go to bed much later, his body shifts to a different circadian rhythm on the weekend. • Then on Monday, when he has to return back to work, he has mini jet lag and is suffering from social jet lag. • These patients have activation of the hypothalamic-pituitary-adrenal axis.

29. How to Defeat the 3 Ss • You may think that there is not that much to do to overcome these physiological effects leading to weight gain--stress, sleep and social jet lag. • However, although nobody has a stress-free life, the trick is not to let stress effect you. • Be one of those people that have the stress just bounce off you. • Also, avoid stressful situations.

30. How to Defeat the 3 Ss • In terms of sleep, try to get both a good quality and a good quantity of sleep. • Try to avoid alcohol and caffeine at night as well. • Avoid electronics at night.

31. How to Defeat the 3 Ss • Finally, for the social jet lag, you may need to get a job that can accommodate your circadian rhythm. • You can try to adjust your circadian rhythm in that if you are a night owl you can try to be exposed to sunlight in the morning and avoid sunlight in the evening. • Trying to tackle the three Ss and controlling your cortisol level is the key to good hormone health.

32. Food Time Restriction A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans that Can Be Modulated for Health Benefits Cell. Metabolism, 22, 789–798, November 3, 2015.

33. Food Time Restriction

34. Food Time Restriction • The daily eating pattern in healthy adults is highly variable from day to day • More than half of the adults eat for 15 hr or longer every day • Sleep duration parallels the fasting duration • Reducing the daily eating duration can contribute to weight loss • Don’t eat at night!

35. Why is it so hard to lose weight • I hate to say this, but most people gain weight as they age. • Thrifty gene hypothesis: Humans lived for millions of years in times of scarcity. • Hormones-leptin, insulin, cortisol, have evolved to prevent starvation. • Thyroid, reproductive and GH axis are shut down in times of starvation. • Now food is abundant, but we still have our hormones designed to prevent starvation.

36. Why is it so hard to lose weight • Abundance of high caloric, unhealthy foods • Healthy foods are more expensive • Less time to exercise • Sedentary lifestyles • Sleep deprivation • Stress

37. What can I do to lose weight • Low/no carb, lean protein, mostly vegetable diet (Paleo diet) • Avoid processed foods and simple carbs • Get an app and track your food intake • 1200-1400 cals for women, 1400-1600 cals in men • Avoid eating at night • Avoid stress eating

38. What can I do to lose weight • Exercise 30-60 min a day-longer if you can • Eat high a fiber, low glycemic diet • Get at least 7-8 hours of sleep at night • Avoid and learn to deal with stress

39. Visit goodhormonehealth.com • For more information or to schedule an appointment. • Talk will posted in a few days • mail@goodhormonehealth.com

40. Thanks • Magic Foundation for inviting me and doing great work! • Great job Dianne