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Old 03-11-13, 06:56 AM
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Arrow Lack of Leptin and Dopamine causing weight gain/obesity

I just watched a special on TV about the newest study findings about obesity and why some of us tend to overeat on a regular basis.


Scientists recently have found the ‘gluttony gene’ which fails to tell your brain when you are full.

It was said that obese people are lacking a hormone called Leptin or they lack the receptor to the hormone Leptin.
High levels of Leptin activate nerve cells in the brain and create a feeling of fullness, while low levels signal hunger. Studies also showed that humans who lack/ have low levels of Leptin eat large amounts of food because they do not experience that feeling of fullness and end up extremely obese.

According to recent study findings, obese people also tend to have fewer receptors for the neurotransmitter Dopamine than people without weight problems, implying that obese people/overeaters may eat more to try to stimulate Dopamine pleasure circuits in their brains, just as drug addicts do by taking drugs.

The lack or low production of Leptin also causes an overproduction of Cortisol.
Cortisol is a hormone that is released within the body that works to break down body tissues. In times of stress, you will find cortisol levels very high since the body is getting ready for the fight or flight response mechanism.
Prolonged high Cortisol is the cause of Cushing's Syndrome.* The main symptoms of this disease is obesity, high blood pressure, high blood sugar, depression, anxiety among others.

*Cushing's Syndrome:
http://www.medicinenet.com/cushings_...me/article.htm


There are a bunch of published data in medical journals on these studies online, but I found the info in this link easier to read and understand.

http://www.dana.org/news/publication....aspx?id=14420

I've put together some useful excepts for a quicker read:

Research on appetite control in the 1970s and 1980s focused on two neurotransmitters, norepinephrine and serotonin. Both are messenger chemicals that travel across the synaptic gap between neurons. Doctors prescribed amphetamines to enhance the release of norepinephrine and thereby control appetite, and targeted serotonin for its role at the hypothalamic control centers for appetite. However, the discovery of two important hormones in the 1990s led to a finer understanding of how appetite is controlled and how, when something goes awry, obesity can occur.
In 1994 Rockefeller University researcher Jeffrey Friedman and his colleagues published a landmark paper in Nature that identified a hormone called leptin (Greek for “thin”) produced by the obese (ob) gene. Leptin is made by the body’s fat cells, which help to regulate food intake and energy expenditure (the amount of calories we burn). Friedman showed that mice lacking the ob gene do not produce leptin and become extremely obese. After both normal and ob-deficient mice were injected with synthetic leptin, they became more active and lost weight.
High levels of leptin activate nerve cells in the brain and create a feeling of fullness, while low levels signal hunger. Friedman also showed that humans who lack the ob gene and eat large amounts do not experience that feeling of fullness and end up extremely obese.



Five years after Friedman’s discovery, Japanese researchers identified another hormone, ghrelin, which they called the “hunger hormone.” Ghrelin is made in the stomach and tells our brain when it’s time to eat. Ghrelin levels rise just before mealtime and fall after we eat.



Research studies are currently under way to examine the underlying psychology and biology behind this hypothesis. Some of these studies have focused on the neurotransmitter dopamine, which plays a role in the brain’s reward circuit. In 2001, researchers at Brookhaven National Laboratory reported that obese people have fewer receptors for dopamine than people without weight problems, implying that obese people may eat more to try to stimulate dopamine pleasure circuits in their brains, just as drug addicts do by taking drugs.



In 2008, scientists at Eli Lilly and the University of Texas Southwestern Medical Center independently discovered an enzyme that is responsible for putting a fatty acid on ghrelin, the so-called hunger hormone. Without this fatty acid, ghrelin might not have the same effect on appetite. The identification of this enzyme, called GOAT, or ghrelin O-acyl transferase, is the first step toward developing medications to treat obesity.
Ever since ghrelin was discovered, scientists have sought ways to manipulate the hormone to help tame hunger. With the discovery of GOAT, researchers are now testing compounds that block the enzyme from attaching to ghrelin. One promising approach uses antibodies to sop up the enzyme and block ghrelin signals to the brain.



The anti-obesity drugs include rimonabant, marketed by Sanofi-Aventis under the trade name Acomplia, which has been approved for weight loss in Europe and awaits approval by the Food and Drug Administration (FDA) for use in the United States.
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Last edited by starry; 03-11-13 at 07:08 AM..
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Old 03-11-13, 07:19 AM
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Re: Lack of Leptin and Dopamine causing weight gain/obesity

What is Leptin?

Leptin (Greek λεπτός (leptos) meaning thin) is a 16-kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite/hunger and metabolism.

Function:
Leptin acts on receptors in the hypothalamus of the brain, where it inhibits appetite
1. counteracting the effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut and in the hypothalamus)
2. counteracting the effects of anandamide (another potent feeding stimulant that binds to the same receptors as THC)
3. promoting the synthesis of α-MSH, an appetite suppressant.
This appetite inhibition is long-term, in contrast to the rapid inhibition of eating by cholecystokinin (CCK) and the slower suppression of hunger between meals mediated by PYY3-36. The absence of leptin (or its receptor) leads to uncontrolled food intake and resulting obesity. Several studies have shown fasting or following a very-low-calorie diet (VLCD) lowers leptin levels.
In the short-term, leptin might be an indicator of energy balance. This system is more sensitive to starvation than to overfeeding; leptin levels change more when food intake decreases than when it increases.
The dynamics of leptin due to an acute change in energy balance may be related to appetite and eventually to food intake. Although this is a new hypothesis, some data already support it.
Controversy is ongoing regarding the regulation of leptin by melatonin during the night. One research group suggested increased levels of melatonin caused a downregulation of leptin. However, in 2004, Brazilian researchers found melatonin to increase leptin levels in the presence of insulin, therefore causing a decrease in appetite during sleeping.
Mice with type 1 diabetes treated with leptin alone or in conjunction with insulin did better (blood sugar did not fluctuate as much; cholesterol levels decreased; less body fat formed) than those treated with insulin alone, raising the prospect of a new treatment for diabetes.

Interaction with amylin
Coadministration of two neurohormones known to have a role in body weight control, amylin (produced by beta cells in the pancreas) and leptin (produced by fat cells), results in sustained, fat-specific weight loss in a leptin-resistant animal model of obesity.

Leptin signals the brain that the body has had enough to eat, producing a feeling of satiety. Moreover, this fullness hormone may make it easier for people to resist the temptation of foods high in calories.

http://en.wikipedia.org/wiki/Leptin
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Old 03-12-13, 12:01 PM
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Re: Lack of Leptin and Dopamine causing weight gain/obesity

Yeah it was found that mice that are breed with the knock out gene for leptin was much more obese. They also seem to be more lethargic but that could be just related to being obese than just the leptin affecting the brain. But in a UK study where they injected people with leptin, only a few benefited from the increased leptin. So this suggest that is possible that lack leptin alone does not cause obesity. So your information on the other neurochemicals is very interesting. It could also mean that there are people who also have an defective leptin receptor gene.

There was also a study where there could also be a virus that causes fat cells to over produce which in turn causes obesity. It was found in some chickens and in theory, humans could get the same virus. Flu was orginally an avian virus so it may be possible that this "fat virus" could have cross the inter-species barrier. Obesity studies are amazing. So many crazy variables.
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Old 03-12-13, 12:20 PM
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Re: Lack of Leptin and Dopamine causing weight gain/obesity

This was quite the informative read. It seems possible that obese people could get leptin injections to help fight off their obesity. Im glad you posted this, thanks for the info
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Old 03-12-13, 07:39 PM
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Re: Lack of Leptin and Dopamine causing weight gain/obesity

Quote:
Originally Posted by deadmau5 View Post
This was quite the informative read. It seems possible that obese people could get leptin injections to help fight off their obesity. Im glad you posted this, thanks for the info
My pleasure

Actually there's been a study recently on human subjects, injecting them with Leptin, but due to skin problems and tissue damage on the injection sites (like skin irritations as well as cell death) most subjects have dropped out of the study, so it couldn't be completed.

I hope they can figure out a way to inject it, that won't cause tissue damage and/or skin irritations...

Or maybe take it orally instead inside sealed off enteric coated capsules (to avoid getting dissolved by the stomach acids) instead of injections??
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Old 03-12-13, 07:54 PM
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Re: Lack of Leptin and Dopamine causing weight gain/obesity

Quote:
Originally Posted by mrsleepy View Post
Yeah it was found that mice that are breed with the knock out gene for leptin was much more obese. They also seem to be more lethargic but that could be just related to being obese than just the leptin affecting the brain. But in a UK study where they injected people with leptin, only a few benefited from the increased leptin. So this suggest that is possible that lack leptin alone does not cause obesity. So your information on the other neurochemicals is very interesting. It could also mean that there are people who also have an defective leptin receptor gene.

There was also a study where there could also be a virus that causes fat cells to over produce which in turn causes obesity. It was found in some chickens and in theory, humans could get the same virus. Flu was orginally an avian virus so it may be possible that this "fat virus" could have cross the inter-species barrier. Obesity studies are amazing. So many crazy variables.

Yes, I've read about the "obesity" virus. It's terrifying to know such a virus exists.

Also another factor could be due to a tumor in the brain, that is blocking the Leptin receptor.
This was actually a case with one of the patients, on the TV special I watched.
She was totally thin, with no eating disorders until her 30's.
She mysteriously developed severe "obesity" out of the blue and gained enormous amounts of weight, since she could no longer get that signal from her brain telling her to stop eating because she's had eaten enough, so she kept eating and eating. No family history in obesity, or other eating disorders.
Tests showed she had a tumor in her brain, right where the Leptin receptors were.
She had it the tumor removed via surgery and soon after the overeating became less.
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