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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May 14,2020

COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections, say scientists who have decoded the mechanisms, symptoms, and diagnosis of the disease caused by the SARS-Cov-2 coronavirus.

In a study published in the journal Frontiers in Public Health, the researchers explained step-by-step how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defences to overshoot with a "cytokine storm".

This storm is an over-activation of white blood cells, which release too-great amounts of cytokines -- inflammation-stimulating molecules --into the blood, they said.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome," said study author Daishun Liu, Professor at Zunyi Medical University in China.

"The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," Liu said.

The researchers explained that the cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, and blood clotting inside the body.

It also causes extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs, they said.

The researchers noted that white blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals.

This multiple organ dysfunction syndrome (MODS) may worsen and shutdown the lungs, a condition called acute respiratory distress syndrome, (ARDS), they said.

This, the researchers explained, happens due to the formation of a so-called hyaline membrane -- composed of debris of proteins and dead cells -- lining the lungs, which makes absorption of oxygen difficult.

Most deaths due to COVID-19 are therefore due to respiratory failure, they said.

The researchers explained that in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, and lowering the mortality rate through intensive maintenance of organ function.

For example, an artificial liver blood purification system or renal replacement therapy can be used to filter the blood through mechanical means, they said.

The team noted that especially important are methods to supplement or replace lung function, for example with non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe, the administration of heated and humidified oxygen via a tube in the nose, or a heart-lung bypass.

The researchers stressed the importance of preventing secondary infections.

They noted that SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.

The researchers advocate that this should be prevented with nutritional support, for example with probiotics -- beneficial bacteria that protect against the establishment of harmful ones -- and nutrients and amino acids to improve the immune defences and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," Liu added.

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June 10,2020

Early treatment with the antiviral drug remdesivir has been found to reduce viral load and prevent lung disease in macaques infected with SARS-CoV-2 that causes COVID-19, according to a study.

The findings, published in the journal Nature on Tuesday, support the early use of remdesivir treatment in patients with COVID-19 to prevent progression to pneumonia.

Researchers from the National Institutes of Health in the US noted that remdesivir has broad antiviral activity and has been shown to be effective against infections with SARS-CoV and MERS-CoV in animal models.

The drug is being tested in human clinical trials for the treatment of COVID-19, they said.

Researcher Emmie de Wit and colleagues investigated the effects of remdesivir treatment in rhesus macaques, a recently established model of SARS-CoV-2 infection.

Two sets of six macaques were inoculated with SARS-CoV-2.

One group was treated with remdesivir 12 hours later -- close to the peak of virus reproduction in the lungs -- and these macaques received treatment every 24 hours until six days after inoculation.

In contrast to the control group, the researchers found that macaques that received remdesivir did not show signs of respiratory disease, and had reduced damage to the lungs.

Viral loads in the lower respiratory tract were also reduced in the treated animals; viral levels were around 100 times lower in the lower-respiratory tract of remdesivir-treated macaques 12 hours after the first dose, they said.

The researchers said that infectious virus could no longer be detected in the treatment group three days after initial infection, but was still detectable in four out of six control animals.

Despite this virus reduction in the lower respiratory tract, no reduction in virus shedding was observed, which indicates that clinical improvement may not equate to a lack of infectiousness, they said.

Dosing of remdesivir in the rhesus macaques is equivalent to that used in humans, the researchers noted.

They cautioned that it is difficult to directly translate the timing of treatment used in corresponding disease stages in humans, because rhesus macaques normally develop only mild disease.

However, researchers said the results indicate that remdesivir treatment of COVID-19 should be initiated as early as possible to achieve the maximum treatment effect.

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May 6,2020

Washington D.C., May 5: Working from home has become the new normal ever since the outbreak of coronavirus and in today's time the work duties can be easily dealt with by means of mobile devices at home.

However, this easy use of technology, mobile devices for that matter, has the potential to blur the fine line between work and the other daily life routines.

But, contrary to the belief, a study at the University of Jyvaskyla reveals that the mixing of work and other daily life routines may have more benefits than previously assumed, and points to the importance of boundary-spanning communication.

A smartphone enables phone calls, email, and file transfers from the comfort of home. The study shows that there may be more effective ways to maximise the benefits of smartphone use, without diminishing employees' flexibility and the use of these technologies.

"People often forget to talk about positive effects, such as autonomy and freedom the employees gain when they have the flexibility to schedule their work," said Postdoctoral Researcher Ward van Zoonen from JYU, who with his colleagues examined the use of smartphones for work matters outside working hours.

The study paid special attention to the benefits of talking about domestic matters with the immediate supervisor outside the working hours given to an employee.

"This reduces the conflict between work and other life," van Zoonen said.

"If people in an organisation strive for more dialogue between employees' different life domains, it is possible to create a functional environment where people can talk about different matters."

The research findings show that when employees communicate across boundaries and talk at work about their life in other respects, they can receive new kinds of support and understanding from their immediate supervisor.

"This kind of communication creates a low threshold for contacting one's supervisor, which helps employees build a balance between the different domains of their lives and strengthens their organisational identification," said Professor Anu Sivunen describing the findings.

This means that tight working time restrictions to protect employees might not be beneficial after all, if they hinder reaching the positive results indicated in this research.

For the study, a survey was taken of 367 employees who were asked questions such as -- how much they talk about their work with their family, and how much they talk about their family with their immediate supervisor.

"Both supervisors and their employees answered the surveys, and the study actually focused on their mutual communication," Sivunen said.

"Usually people at workplaces are interested in how communication within the work community is succeeding. It is often forgotten how an immediate supervisor can take an employer's other life into account and thereby help the employee gain work-related benefits."

"Communication with one's immediate supervisor during flexible working hours, also on matters other than work, could ease the daily lives of many employees if they could share the possible challenges of their family life or free time with their supervisor in these settings," Sivunen added.

According to the study, such a practice could make the supervisor aware of the employee's situation as he/she works from home and the related impacts on their work performances.

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