Transcript How Pituitary Hormones Affect Weight and Sleep

Theodore C. Friedman, M.D., Ph.D.
(the Wiz)
Professor of Medicine-UCLA
Chairman, Department of Internal Medicine
Charles R. Drew University
Dr. Friedman’s Endocrinology Clinic
How Pituitary Hormones Affect Weight and Sleep
MAGIC Adult Convention
Chicago, IL
July 22, 2016
What causes weight gain?
• More calories intake than calories
expended.
• Duh Dr. Friedman, that’s not why I
came to Chicago.
What causes weight gain?
• The 3 Ss
– Sleep Deprivation
– Stress
– Social Jet Lag
• Lack of food-time restriction
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
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.
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.
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.
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
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”
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.
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.
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
How does insulin lead to weight gain?
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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
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
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.
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.
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.
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.
Growth hormone
• In patients that are growth hormone deficient
(confirmed by a growth hormone stimulation test),
growth hormone treatment leads to:
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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 hormonedeficient may benefit from serovital.
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
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 perimenopausal and menopausal women.
Poor Sleep
• Low estrogen leading to poor sleep may
lead to diabetes and obesity.
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.
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.
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.
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.
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.
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 hypothalamicpituitary-adrenal axis.
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.
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.
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.
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.
Food Time Restriction
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!
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.
Why is it so hard to lose weight
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Abundance of high caloric, unhealthy foods
Healthy foods are more expensive
Less time to exercise
Sedentary lifestyles
Sleep deprivation
Stress
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
What can I do to lose weight
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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
Visit goodhormonehealth.com
• For more information or to schedule an
appointment.
• Talk will posted in a few days
• [email protected]
Thanks
• Magic Foundation for inviting me
and doing great work!
• Great job Dianne