Biological Bases For Obesity & Thinness

ramonmercado

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There May Be A Biological Basis In The Brain For Being Obese And A Couch Potato

Main Category: Obesity / Weight Loss / Fitness News
Article Date: 17 Aug 2006 - 19:00pm (PDT)

Some brains may be wired to encourage fidgeting and other restless behaviors that consume calories and help control weight, according to new research published by The American Physiological Society.

The study found that the brains of rats bred to be lean are more sensitive to a chemical produced in the brain, orexin A, which stimulates appetite and spontaneous physical activity such as fidgeting and other unconscious movements. Compared to rats bred to be obese, the lean rats had a far greater expression of orexin receptors in the hypothalamus.

"The greater expression of orexin receptors suggests the lean rats' brains were more sensitive to the orexin the brain produces," said Catherine M. Kotz, the study's senior researcher. "The results point to a biological basis for being a couch potato."

This line of research suggests that frequent minor unconscious movements such as fidgeting and other behaviors associated with restlessness burn calories and help control weight, Kotz said. Further, it suggests a strategy to reduce weight gain and could lead to the development of a drug to stimulate minor activity.

The study "Elevated hypothalamic orexin signaling, sensitivity to orexin A and spontaneous physical activity in obesity resistant rats," appears in the online edition of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology published by The American Physiological Society. The study was done by Jennifer A. Teske and Allen S. Levine of the University of Minnesota and the Minnesota Obesity Center, St. Paul; Michael Kuskowski, VA Medical Center, Minneapolis; James A. Levine, Mayo Clinic, Rochester, Minnesota; and Catherine M. Kotz, the VA Medical Center, University of Minnesota, and the Minnesota Obesity Center.

Study looks at obese versus lean rats

"Many people focus on diet, but it may be more feasible for some people to stand or move more throughout the day" as a way to control their weight, Kotz said. Contrary to common belief, metabolism rates don't vary greatly from person to person and weight gain usually results from eating too much, burning too few calories, or both, she said.

The researchers drew their conclusions after performing a series of experiments with obesity-prone and obesity-resistant rats. The obesity-prone strain was developed for obesity research by breeding obese rats with other obese rats. The obesity-resistant rats were developed by breeding lean rats with lean rats, Kotz noted. The study also employed a control group of normal laboratory rats.

Each rat consumed the same number of calories each day. The researchers took baseline measurements of each rat's activity using sensors to measure even minor movements, such as grooming and standing.

They found that the lean group moved significantly more during this baseline period than the obese group, Kotz said. This was true even though the rats were young and both groups weighed the same -- eliminating the obesity itself as the cause of the decreased movement. After the baseline data gathering, the researchers moved to the experimental part of the study.

Lean rats have elevated expression of orexin receptors

"We knew from previous studies that orexin stimulated physical activity, and so we wanted to find out whether it enhances activity more in lean rats than in obese rats, Kotz explained. The researchers injected orexin into the lateral hypothalamus area of the brains of both groups and found that the lean rats became even more active, while the obese rats didn't respond much at all. "Not only do the lean rats have a higher base activity rate but they respond more to orexin," she said.

Orexin must bind to receptors in the brain to produce increased activity, so the researchers reasoned that the lean rats must have more orexin receptors. When they did a blind analysis of the brains of obese and lean rats of various ages, they found that the lean rats had double the gene expression level of orexin receptors compared to the obese rats, Kotz explained.

The greater gene expression of orexin receptors does not conclusively prove that there are more orexin receptors, but it is highly suggestive of that finding. Kotz and her fellow researchers are now looking to see if the lean rats have a greater number of orexin receptors in their brains.

Activity level important to weight control

Because the rats in this study ate the same amount of food, the researchers concluded that the weight gain of the obese rats comes more from expending too few calories than from consuming too many. Other studies have shown that disabling the orexin system of lean rats causes them to eat less and move less, which leads them to become obese, Kotz said. When the orexin system is working optimally, the increase in eating which orexin causes is believed to be offset by increased physical activity, she said.

It would be impossible to do a similar study of the brain in humans. But one of the researchers, James Levine, found in a previous study with humans that lean individuals move about two hours per day more than obese individuals. What does this mean for those who are overweight?

"If we can get obese individuals to a slightly higher level of activity, that would be very beneficial," Kotz concluded.

###

Future studies will focus on:

* Counting the number of orexin receptors in the brains of lean versus obese rats

* Enhancing orexin in obese rats to see if they moderate their weight gain

Funding

Funding was provided by the Minnesota Department of Employment and Economic Development (Minnesota Partnership for Biotechnology and Medical Genomics), the U.S. Department of Veterans Affairs and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has 10,500 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.

APS provides a wide range of research, educational and career support and programming to further the contributions of physiology to understanding the mechanisms of diseased and healthy states. In 2004, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring.

Contact: Christine Guilfoy
American Physiological Society
http://www.the-aps.org/
http://www.medicalnewstoday.com/medical ... wsid=49685
 
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rynner2

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Clear obesity gene link 'found'

Scientists say they have identified the clearest genetic link to obesity yet.
They found people with two copies of a "fat" version of a gene had a 70% higher risk of obesity than those with none, and weighed 3kg (6.5lb) more.

The work in Science by the Peninsula Medical School and Oxford University studied data from about 40,000 people.

The findings suggest that although improving lifestyle is key to reducing obesity, some people may find it harder to lose weight because of their genes.

The authors say their work, funded by the Wellcome Trust, could improve understanding of obesity and eventually help prevent it, as well as an illness it is linked to.

Genome differences

Obesity is associated with an increased risk of type two diabetes, and the investigators first identified the FTO gene when looking for differences between the genomes of people with type two diabetes and people without diabetes.

People with type two diabetes were more likely to have a particular variant of the FTO gene, which was also shown to be linked to increased body weight.

The variant making people fatter differed from the other version of the FTO gene by a single mutation in the DNA sequence.

The team then looked at other studies involving 40,000 people searching for this FTO mutation, and confirmed that it was associated with body weight.

People carrying one copy of the "fat" FTO variant had a 30% increased risk of being obese compared to a person with no copies of that version.

Those carrying two copies of the variant had a 70% increased risk of being obese, and were on average 3kg (6.6lb) heavier than a similar person with no copies.

Professor Andrew Hattersley of the Peninsula Medical School said this could explain why two people can seem to eat the same things and do the same amount of exercise yet one may struggle to lose weight more than the other.

He said: "The typical message has been that if you are overweight it is due to sloth and gluttony and it is your fault.

"This work is suggesting that there is also a genetic component."

And he said although a 3kg difference in weight sounds relatively small, it is enough to make a big change in the risks of obesity.

Improving treatment

Dr Sadaf Farooqi of the Department of Clinical Biochemistry at the University of Cambridge said: "This study is important because it has yielded evidence for the first obesity susceptibility gene.

"Understanding the genetic susceptibility to weight gain will make an important contribution to the prevention and treatment of obesity."

The team does not yet know exactly what the FTO gene does or how the different variants work to influence body weight.

But they hope further research to understand the gene may lead to the unravelling of the basic biology of obesity.

Dr Mark Walport, director of the Wellcome Trust, said this could have very helpful consequences for public health as about one in six white Europeans carried two copies of the variant.

Obesity is one of the most challenging problems for public health in the UK," he said.

"The discovery of a gene that influences the development of obesity in the general population provides a new tool for understanding how some people appear to gain weight more easily than others."

http://news.bbc.co.uk/1/hi/health/6547891.stm
See! I told you it was my genes! :D
 

witchflame

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They'll be the genes and viruses that cause said persons to move their arm, open there gaping maw and fill it full of frigging crap 24/7 then. I've met plenty of 'em and they just cannot see that their constant shovelling is whats causing their condition not their 'genes', 'viruses' or (and this is my personal favourite) 'glands!'. PIES PIES PIES!!! ;) :lol: :twisted:
 

rynner2

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It confirms my prejudices about certain types of people to see that they can ignore scientific evidence against their prejudices about certain types of people... 8)
 

Rrose_Selavy

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Genetic disposition rarely means fatalistic inevitability - in other words. just because some people might have a natural tendency to be obese -or doesn't mean they have to be., though it may make it relatively more difficult than others to keep to healthy weight.

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crunchy5

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It's reckoned by someone speaking on rad 5 that 16% of the UK pop have the gene in question, but iirc 70% of the UK pop are over weight, hmm.
 

witchflame

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rynner said:
It confirms my prejudices about certain types of people to see that they can ignore scientific evidence against their prejudices about certain types of people... 8)
well rynner, now I'm confused :lol:
It was meant to be tongue in cheek. But I'm sure you have come across the aformentioned 'type' in your lifetime also. :mrgreen:
 

elvissa

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In some ways, the news seems fairly obvious, because a tendency to gain weight can be seen to run (or slouch) in families. So it must be genetic.

The other thing I feel I have to say though is that when people say "obese", do they mean according to the BMI scale? Which is actually quite cobblers-esque? Because apparently a footballer like Sol Campbell could be considered "obese" on the BMI scale, as it doesn't take into account that weight might be caused by muscle, instead of fat.

I however do not have that excuse. A sedentary job and a fondness for chocolate doesn't equal a size zero.
 

ramonmercado

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Next Generation: Fat-Targeted Gene Knockdown
A small peptide helps a silencing construct home in on the adipocytes of obese mice.

The technique: A specific short peptide aimed at fat cells can deliver a DNA sequence that knocks down expression of a key fatty acid binding protein. Mice on a high-fat diet treated with this molecular complex showed reduced body weight and improved metabolic profiles. The method, reported today (October 5) in Nature Materials, provides a new way to study the functions of adipocytes—a notoriously intractable cell type—and suggests an avenue for gene therapy to combat obesity in humans.

“It’s always welcome when there is a new technology to deliver specific targeting molecules, whether they’re RNAi or small molecules, to restricted parts of the body,” said Gökhan Hotamisligil, a professor at the Harvard School of Public Health who was not involved in the study. Hotamisligil, who investigates the regulation of glucose and lipid metabolism, added that drug molecules or other broad strategies used to modulate lipid metabolism frequently have off-target effects on the liver or central nervous system. ...

http://www.the-scientist.com/?articles. ... Knockdown/
 

ramonmercado

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A whole new meaning for fathead...

From middle-age, the brains of obese individuals display differences in white matter similar to those in lean individuals ten years their senior, according to new research led by the University of Cambridge. White matter is the tissue that connects areas of the brain and allows for information to be communicated between regions.

Our brains naturally shrink with age, but scientists are increasingly recognising that obesity - already linked to conditions such as diabetes, cancer and heart disease - may also affect the onset and progression of brain ageing; however, direct studies to support this link are lacking.

In a cross-sectional study - in other words, a study that looks at data from individuals at one point in time - researchers looked at the impact of obesity on brain structure across the adult lifespan to investigate whether obesity was associated with brain changes characteristic of ageing. The team studied data from 473 individuals between the ages of 20 and 87, recruited by the Cambridge Centre for Aging and Neuroscience. The results are published in the journal Neurobiology of Aging.

The researchers divided the data into two categories based on weight: lean and overweight. They found striking differences in the volume of white matter in the brains of overweight individuals compared with those of their leaner counterparts. Overweight individuals had a widespread reduction in white matter compared to lean people.

The team then calculated how white matter volume related to age across the two groups. They discovered that an overweight person at, say, 50 years old had a comparable white matter volume to a lean person aged 60 years, implying a difference in brain age of 10 years. ...

http://medicalxpress.com/news/2016-08-brains-overweight-people-ten-years.html
 

EnolaGaia

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Researchers have identified a gene that seems to be the key factor in allowing some folks to eat whatever they want without ever gaining any weight.
Scientists Identify Gene Linked to Thinness – Unique to People That Can Eat Anything and Not Gain Weight

While others may be dieting and hitting the gym hard to stay in shape, some people stay slim effortlessly no matter what they eat. In a study publishing today (May 21, 2020) in the journal Cell, researchers use a genetic database of more than 47,000 people in Estonia to identify a gene linked to thinness that may play a role in resisting weight gain in these metabolically healthy thin people. They show that deleting this gene results in thinner flies and mice and find that expression of it in the brain may be involved in regulating energy expenditure.

“We all know these people: it’s around one percent of the population,” says senior author Josef Penninger, the director of the Life Sciences Institute and professor of the department of medical genetics at the University of British Columbia. “They can eat whatever they want and be metabolically healthy. They eat a lot, they don’t do squats all the time, but they just don’t gain weight.

“Everybody studies obesity and the genetics of obesity,” he says. “We thought, ‘Let’s just turn it around and start a new research field.’ Let’s study thinness.”

Penninger’s team looked at data from the Estonian Biobank, which includes 47,102 people aged 20 to 44 years old. The team compared the DNA samples and clinical data of healthy thin individuals with normal-weight individuals and discovered genetic variants unique to thin individuals in the ALK gene. ...

The researchers say that therapeutics targeting the gene might help scientists fight obesity in the future. “If you think about it, it’s realistic that we could shut down ALK and reduce ALK function to see if we did stay skinny,” says Penninger. “ALK inhibitors are used in cancer treatments already. It’s targetable. We could possibly inhibit ALK, and we actually will try to do this in the future.” Further research will be required to see if these inhibitors are effective for this purpose. The team also plans to further study how neurons that express ALK regulate the brain at a molecular level to balance metabolism and promote thinness. ...
FULL STORY: https://scitechdaily.com/scientists...le-that-can-eat-anything-and-not-gain-weight/
 
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