High fat diet may cause changes in the brain: study

October 24, 2016

Washington, Oct 24: In a recent study, scientists have discovered a new mechanism that regulates obesity. The study shows that this new mechanism can potentially be targeted to treat obesity.

highfatSenior author of the study Makoto Fukuda said, "It's well known that the brain is involved in the development of obesity, but how a high-fat diet changes the brain so it triggers the accumulation of body fat is still unclear."

The team studied the mouse Rap1 gene, which is expressed in a variety of tissues, including the brain where it is involved in functions such as memory and learning. Little was known, however, of the role brain Rap1 plays in energy balance.

To explore the role Rap1 plays in a mouse model, the scientists selectively deleted the Rap1 gene in a group of neurons in the hypothalamus, a region of the brain that is involved in regulating whole-body metabolism.

The scientists had two groups of mice. In one group, the mice were genetically engineered to lack the Rap1 gene, while the control group had a functional Rap 1 gene. Then, the scientists fed the mice in both groups a high-fat diet in which 60 percent of the calories came from fat.

As expected, the control mice with a working Rap1 gene gained weight, but, in comparison, the mice that lacked Rap 1 had markedly reduced body weight and less body fat. Interestingly, when both groups of mice were fed a normal diet, both showed similar weights and body fat.

The scientists then looked closer at why the mice lacking the Rap1 gene had not gained weight despite eating a high-fat diet.

"We observed that the mice lacking Rap1 were not more physically active. However, they ate less and burned more body fat than mice with Rap1," said Fukuda.

Adding, "These observations were associated with the hypothalamus producing more of a hormone that reduces appetite, called POMC, and less of hormones that stimulate appetite, called NPY and AgRP." These mice also had lower levels of blood glucose and insulin than controls.

The scientists also were interested in studying whether leptin changed in mice lacking Rap1.

Leptin, the 'satiety hormone' produced by fatty tissue, helps regulate body weight by inhibiting appetite. Obese people, however, do not respond to leptin's signals of satiety, and the blood levels of leptin are higher than those in non-obese people. Leptin resistance is a hallmark of human obesity.

Mice that lacked Rap1 and ate a high-fat diet, on the other hand, did not develop leptin resistance; they were able to respond to leptin and this was reflected in the hormone's lower blood levels.

The team also tested the effect of inhibiting Rap1 with drugs instead of deleting the gene on mice on a high-fat diet. The scientists inhibited RAP1 action with inhibitor ESI-05.

"When we administered ESI-05 to obese mice, we restored their sensitivity to leptin to a level similar to that in mice eating a normal diet. The mice ate less and lost weight," he said.

The scientists have shown a new mechanism by which the brain can affect the development of obesity triggered by consuming a high-fat diet.

Consuming a high-fat diet results in changes in the brain that increase Rap1 activity, which in turn leads to a decreased sensitivity to leptin, and this sets the body on a path to obesity.

"This new mechanism involving Rap1 in the brain may represent a potential therapeutic target for treating human obesity in the future," said Fukuda.

The study appeared in Cell Reports today.

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Agencies
April 4,2020

Washington D.C., Apr 4: While consuming a high-diet salt can result in high blood pressure, a recent study has revealed a link between salt-rich diet and weaker immune system.

The study was conducted under the leadership of the University Hospital Bonn, and the results were published in the journal Science Translational Medicine.

The research was conducted on mice that were fed a high-salt diet. Later, they were found to suffer from much more severe bacterial infections.

Human volunteers who consumed an additional six grams of salt per day also showed pronounced immune deficiencies.

The World Health Organization (WHO) has recommended a maximum amount of five grams of salt a day.

It corresponds approximately to one level teaspoon. In reality, however, many Germans exceed this limit considerably. 

Figures from the Robert Koch Institute suggest that on average men consume ten, and women more than eight grams a day.

This means that we reach for the salt shaker much more than is good for us. After all, sodium chloride, which is its chemical name, raises blood pressure and thereby increases the risk of heart attack or stroke.

"We have now been able to prove for the first time that excessive salt intake also significantly weakens an important arm of the immune system," said Prof. Dr. Christian Kurts from the Institute of Experimental Immunology at the University of Bonn.

This finding is unexpected, as some studies point in the opposite direction. For example, infections with certain skin parasites in laboratory animals heal significantly faster if these consume a high-salt diet.

The study also sheds light on the fact that the skin serves as a salt reservoir.

"Our results show that this generalization is not accurate," emphasized Katarzyna Jobin, lead author of the study.

The body keeps the salt concentration in the blood and in the various organs largely constant. Otherwise important biological processes would be impaired. The only major exception is the skin which functions as a salt reservoir of the body. This is why the additional intake of sodium chloride works so well for some skin diseases.

However, other parts of the body are not exposed to the additional salt consumed with food. Instead, it is filtered out by the kidneys and excreted in the urine.

"We examined volunteers who consumed six grams of salt in addition to their daily intake," said Prof. Kurts. This is roughly the amount contained in two fast-food meals, i.e. two burgers and two portions of French fries.

After one week, from the results, it showed that the immune cells coped much worse with bacteria after the test subjects had started to eat a high-salt diet.

In human volunteers, excessive salt intake also resulted in increased glucocorticoid levels.

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Agencies
July 3,2020

Apart from the many benefits of doing exercise, new research has now found that exercise can slow down or prevent the development of macular degeneration and may benefit other common causes of vision loss, such as glaucoma and diabetic retinopathy.

The new study from the University of Virginia School of Medicine found that exercise reduced the harmful overgrowth of blood vessels in the eyes of lab mice by up to 45 per cent. This tangle of blood vessels is a key contributor to macular degeneration and several other eye diseases.

The study represents the first experimental evidence showing that exercise can reduce the severity of macular degeneration, a leading cause of vision loss, the scientists report. Ten million Americans are estimated to have the condition.

"There has long been a question about whether maintaining a healthy lifestyle can delay or prevent the development of macular degeneration. The way that question has historically been answered has been by taking surveys of people, asking them what they are eating and how much exercise they are performing," said researcher Bradley Gelfand, PhD, of UVA's Center for Advanced Vision Science.

"That is basically the most sophisticated study that has been done. The problem with that is that people are notoriously bad self-reporters ... and that can lead to conclusions that may or not be true. This [study] offers hard evidence from the lab for the very first time," Gelfand added.

Enticingly, the research found that the bar for receiving the benefits from exercise was relatively low - more exercise didn't mean more benefit.

"Mice are kind of like people in that they will do a spectrum of exercise. As long as they had a wheel and ran on it, there was a benefit. The benefit that they obtained is saturated at low levels of exercise," Gelfand said.

An initial test comparing mice that voluntarily exercised versus those that did not found that exercise reduced the blood vessel overgrowth by 45%. A second test, to confirm the findings, found a reduction of 32 per cent.

The scientists aren't certain exactly how exercise is preventing the blood vessel overgrowth. There could be a variety of factors at play, they say, including increased blood flow to the eyes.

Gelfand, of UVA's Department of Ophthalmology and Department of Biomedical Engineering, noted that the onset of vision loss is often associated with a decrease in exercise.

"It is fairly well known that as people's eyes and vision deteriorate, their tendency to engage in physical activity also goes down. It can be a challenging thing to study with older people. ... How much of that is one causing the other?" he said.
The researchers already have submitted grant proposals in hopes of obtaining funding to pursue their findings further.

"The next step is to look at how and why this happens, and to see if we can develop a pill or method that will give you the benefits of exercise without having to exercise," Gelfand said.

He explained, "We're talking about a fairly elderly population [of people with macular degeneration], many of whom may not be capable of conducting the type of exercise regimen that may be required to see some kind of benefit." (He urged people to consult their doctors before beginning any aggressive exercise program.)
Gelfand, a self-described couch potato, disclosed a secret motivation for the research: "One reason I wanted to do this study was sort of selfish. I was hoping to find some reason not to exercise," he joked. "It turned out exercise really is good for you."

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Agencies
April 14,2020

There is no evidence that the Bacille Calmette-Guerin (BCG) vaccine, which is primarily used against tuberculosis, protects people against infection with the novel coronavirus, the World Health Organization (WHO) said.

The WHO therefore didn't recommend BCG vaccination for the prevention of COVID-19 in the absence of evidence, according to its daily situation report on Monday, Xinhua news agency reported.

"There is experimental evidence from both animal and human studies that the BCG vaccine has non-specific effects on the immune system. These effects have not been well characterized and their clinical relevance remains unknown," WHO stated.

Two clinical trials addressing the question are underway, and WHO will evaluate the evidence when it is available, it noted.

BCG vaccination prevents severe forms of tuberculosis in children and diversion of local supplies may result in an increase of disease and deaths from the tuberculosis, it warned.

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