ANAT 322 Lecture Notes - Lecture 10: Neurosurgery, White Blood Cell, Chemotherapy
7 Jun 2018
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ANAT 322 Winter 2016
Lectures
Lecture 10:
→ Hypothalamic Control of Food Intake
3. Obesity has doubled since 1980 and in 2014 there is about 2 billion people overweight in the world.
4. Obesity is defined as a state of body energy stores (body fat) that exceeds physiological needs. It is
characterized by body mass index (BMI).
5. We can see that over the past 30 years, starting from 1985, obesity population has increased among
US adults. This is also typical for any other developed countries and in Canada.
6. Obesity is co-linked with many chronic diseases and it is the number one predictor of type II diabetes.
It is accompanied by cardiovascular diseases, sleep-breathing abnormalities, gastrointestinal problems
and even cancer.
7. All living organisms obey first law of thermodynamics which means that energy intake should equal
energy expenditure. When energy intake is larger then we expect then body weight will go up. To
control this, one should diet or exercise but still obesity rates are increasing which has stimulated
research to try to find anti-obesity drugs.
8. List of FDA approved medication and these are six medications which are prescribed to obese
patients. The annual sales of all these medications, they make less than 500 million dollars so if we
compare it with the 190 billion per year that people spend in obesity treatments this is a small number
whih akes it lear that these are ot popular. People do’t trust them because all of the anti-obesity
drugs have undesired side effects such as diarrhea, depression, among others.
From an evolutionary point of view, eating behaviors were advantageous for survival so eating
overdrive was normal for bouts of time so the animal could store energy. To develop a drug against
obesity or drugs that reduce appetite is hard because we have to fight millions of year of evolution.
Many researchers say that it will be very hard to find anti-obesity drugs that will target only appetite
ad wo’t affet other physiologial systes.
9. High obesity rates are explained by obesogenic environments which is because food is too accessible,
it is cheap, high in calories and tastes good.
Portion sizes have also increased and what was called king-sized i the 95s is ow kid’s size.
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ANAT 322 Winter 2016
Lectures
When you compared soda with juices as they did in the website for Coca-Cola, it could be misleading
but they do not take into account things like palatability because soda is more palatable than juice in
that juice contains pulp (fiber) or it is more acidic which makes us not want to drink it in really high
quantities. Palatability plays an important role in the development of obesity.
10. The main controlling signal of appetite is in the brain which integrates many signals from the
periphery as well as different parts of the brain. There are two complementary systems that control
appetite and body weight which are the homeostatic system and the hedonic system.
Homeostatic system increases our motivation to eat when energy stores are going down.
Hedonic system is involved in motivation to eat not because of depleting energy stores but because
of pleasure. This system is activated when there is a palatable food around and we eat it because of
pleasure sensation. The main factor responsible for the development of obesity is this system because it
feels good not because we are hungry.
Homeostatic system is controlled by the hypothalamus and the brain stem whereas the hedonic
system is controlled by the ventral tegmental area (VTA).
11. Coronal section of the mouse brain used in obesity research where the hypothalamus is located at
the bottom of the brain. The hypothalamus consists of multiple nuclei such as the arcuate nucleus which
is the most studied (at the bottom), ventromedial and dorsomedial nucleus.
12. First experiments showing that the hypothalamus is involved in energy homeostasis started when
people did lesioning experiments in rodents. They lesioned different areas of the brain by electrical or
chemical lesions with electrodes and they found out that when they lesion the PVN, VMN or DMN, mice
were getting obese. When they lesioned other parts such as the LHA, mice are getting lean. When they
lesioned other parts of the brain there was not so much going on with weight.
13. There were two mice models that developed through spontaneous mutations, so they were not
genetically modified at the beginning, which were the ob/ob mouse and the db/db mouse. These mice
can reach triple size body weight and all they do is eat. If you put them in the cage, they eat until they
cannot move anymore so when they cannot reach the food anymore, they start to lose body weight
until they can move again and keep eating.
In 17th century, Dr. Douglas Coleman did an interesting experiment called parabiosis experiments
which is a surgical union of two individuals so that they share a common blood circulation. He used
these mice in his experiments and he did several pairs of all of them such as wild-type with ob/ob, wild-
type with db/db and ob/ob with db/db.
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ANAT 322 Winter 2016
Lectures
14. Normal mice with ob/ob mice supressed the weight gain of ob/ob mice as they move together all
the time because they moved less and became lean.
Normal mice with db/db mice had no effect on the obese mouse which has a different mutation from
the ob/ob and the normal mouse loses weight and dies of apparent starvation.
Db/db mouse and ob/ob mouse were together and they are both obese with similar weights. Nothing
happened to the db/db mouse whereas the ob/ob mouse reduced food intake and died from starvation.
From these three experiments, he first concluded that there is something in the blood so that when
you put two mice together, one mouse that has this circulating factor shares it with the other mouse. He
concluded that the ob/ob mouse is missing this circulating factor or hormone and the wild-type has this
factor so when you put it together, the ob/ob mice is getting the factor that normalizes the body weight.
His second conclusion was that if you remove a ligand for a receptor, the receptor is upregulated to
overcome the defect in signaling. Therefore, the db/db mouse is missing the receptor which is why there
is a lot of ligand in the mouse and when it is put with the wild-type mouse, the excessive quantity of the
ligand is blocking appetite of the wild-type mouse. The same thing happens when he puts the db/db and
the ob/ob mouse together so that the ligand in db/db mouse blocks appetite of ob/ob mouse who
eventually dies from starvation. So the defects in ob/ob and db/db mice may be in signal and the
receptor for that signal, respectively.
15. About 20 years later these results were confirmed in that the ob/ob mice is deficient in the hormone
named leptin (1994) in which they sequenced the gene for leptin and they saw that the mice had a
deficient gene.
Two years later, there was another paper that showed that the db/db mouse was deficient in the
leptin gene.
17. Ob/ob mouse is missing leptin because the gene is deficient so when they treat the mice with it by
single injection, these will normalize the body weight.
In parabiosis experiment, what happened with the ob/ob + wild-type mice, the leptin being produced
by the wild-type mouse was going to the obese mouse and compensating for the leptin deficiency.
18. Similar situations happen in humans in people with a leptin deficiency and they need daily leptin
injections.
They discovered that the majority of obese patients are insensitive to leptin but have increased leptin
levels in circulation which is called leptin resistant. Leptin levels are going up and at some point the
receptors do not respond so the leptin is not able to reduce appetite and this is still not understood.
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Document Summary
It is characterized by body mass index (bmi): we can see that over the past 30 years, starting from 1985, obesity population has increased among. This is also typical for any other developed countries and in canada: obesity is co-linked with many chronic diseases and it is the number one predictor of type ii diabetes. It is accompanied by cardiovascular diseases, sleep-breathing abnormalities, gastrointestinal problems and even cancer: all living organisms obey first law of thermodynamics which means that energy intake should equal energy expenditure. When energy intake is larger then we expect then body weight will go up. People do(cid:374)"t trust them because all of the anti-obesity drugs have undesired side effects such as diarrhea, depression, among others. From an evolutionary point of view, eating behaviors were advantageous for survival so eating overdrive was normal for bouts of time so the animal could store energy.
