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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News Network
June 20,2020

Washington, Jun 20: Pregnant and postpartum women are usually at a high risk of depression and anxiety - one in seven women struggle with symptoms in the perinatal period and the coronavirus pandemic is exacerbating those struggles according to a recent study.

The study was published in Frontiers in Global Women's Health, which found that the likelihood of maternal depression and anxiety has substantially increased during the health crisis.

"The social and physical isolation measures that are critically needed to reduce the spread of the virus are taking a toll on the physical and mental health of many of us," said Dr. Margie Davenport of the University of Alberta, Canada, who co-authored the study.

For new moms, those stresses come with side effects.

"We know that experiencing depression and anxiety during pregnancy and the postpartum period can have detrimental effects on the mental and physical health of both mother and baby that can persist for years," said Davenport.

Such effects can include premature delivery, reduced mother-infant bonding, and developmental delays in infants.

The study surveyed 900 women - 520 of whom were pregnant and 380 of whom had given birth in the past year - and asked about their depression and anxiety symptoms before and during the pandemic.

Before the pandemic began, 29 percent of those women experienced moderate to high anxiety symptoms, and 15 percent experienced depressive symptoms. During the pandemic, those numbers increased - 72 percent experienced anxiety and 41percent experienced depression.

Because lockdown measures have affected daily routines and access to gyms, researchers also asked women whether their exercise habits had changed. Of the women surveyed, 64 percent reduced their physical activity since the pandemic began, while 15 percent increased and 21 percent experienced no change.

Exercise is a known way to ease depression symptoms, so limited physical activity may result in an uptick in depressive symptoms. Indeed, the study found that women who engaged in at least 150 minutes of moderate physical activity a week had significantly lower symptoms of depression and anxiety.

The findings are somewhat limited given the fact that researchers could not survey women before the pandemic began (since they could not know a pandemic would occur). The women surveyed could only offer their pre-pandemic symptoms in hindsight.

Also, while the researchers asked women about their symptoms using validated measures, only mental health care professionals can validly diagnose an individual with depression or anxiety.

The study was specifically interested in the impact of COVID-19 on new moms, but Davenport says maternal mental health is a critical issue no matter the time.

"Even when we are not in a global pandemic, many pregnant and postpartum women frequently feel isolated whether due to being hospitalized, not having family or friends around or other reasons," she said.

"It is critical to increase awareness of the impact of social (and physical) isolation on the mental health of pregnant and postpartum women," Davenport added.

Increased awareness makes diagnosis and treatment - the ultimate goal - more likely.

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News Network
May 13,2020

California, May 13: A fasting-mimicking diet could be more effective at treating some types of cancer when combined with vitamin C, suggests a new study conducted by the scientists from USC and the IFOM Cancer Institute in Milan.

In studies on mice, researchers found that the combination delayed tumour progression in multiple mouse models of colorectal cancer; in some mice, it caused disease regression. The results were published in the journal Nature Communications.

"For the first time, we have demonstrated how a completely non-toxic intervention can effectively treat an aggressive cancer," said Valter Longo, the study senior author and the director of the USC Longevity Institute at the USC Leonard Davis School of Gerontology and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences.

"We have taken two treatments that are studied extensively as interventions to delay ageing-- a fasting-mimicking diet and vitamin C -- and combined them as a powerful treatment for cancer," added Longo.

The researchers said that while fasting remains a challenging option for cancer patients, a safer, more feasible option is a low-calorie, plant-based diet that causes cells to respond as if the body were fasting.

Their findings suggest that a low-toxicity treatment of fasting-mimicking diet plus vitamin C has the potential to replace more toxic treatments.

Results of prior research on the cancer-fighting potential of vitamin C have been mixed. Recent studies, though, are beginning to show some efficacy, especially in combination with chemotherapy.

In this new study, the research team wanted to find out whether a fasting-mimicking diet could enhance the high-dose vitamin C tumour-fighting action by creating an environment that would be unsustainable for cancer cells but still safe for normal cells.

"Our first in vitro experiment showed remarkable effects. When used alone, fasting-mimicking diet or vitamin C alone reduced cancer cell growth and caused a minor increase in cancer cell death. But when used together, they had a dramatic effect, killing almost all cancerous cells," said Longo.

Longo and his colleagues detected this strong effect only in cancer cells that had a mutation that is regarded as one of the most challenging targets in cancer research.

These mutations in the KRAS gene signal the body is resisting most cancer-fighting treatments, and they reduce a patient's survival rate. KRAS mutations occur in approximately a quarter of all human cancers and are estimated to occur in up to half of all colorectal cancers.

The study also provided clues about why previous studies of vitamin C as a potential anticancer therapy showed limited efficacy. By itself, a vitamin C treatment appears to trigger the KRAS-mutated cells to protect cancer cells by increasing levels of ferritin, a protein that binds iron.

But by reducing levels of ferritin, the scientists managed to increase vitamin C's toxicity for the cancer cells. Amid this finding, the scientists also discovered that colorectal cancer patients with high levels of the iron-binding protein have a lower chance of survival.

"In this study, we observed how fasting-mimicking diet cycles are able to increase the effect of pharmacological doses of vitamin C against KRAS-mutated cancers," said Maira Di Tano, a study co-author at the IFOM, FIRC Institute of Molecular Oncology in Milan, Italy.

"This occurs through the regulation of the levels of iron and of the molecular mechanisms involved in oxidative stress. The results particularly pointed to a gene that regulates iron levels: heme-oxygenase-1," added Tano.

The research team's prior studies showed that fasting and a fasting-mimicking diet slow cancer's progression and make chemotherapy more effective in tumour cells while protecting normal cells from chemotherapy-associated side effects. The combination enhances the immune system's anti-tumour response in breast cancer and melanoma mouse models.

The scientists believe cancer will eventually be treated with low-toxicity drugs in a manner similar to how antibiotics are used to treat infections that kill particular bacteria, but which can be substituted by other drugs if the first is not effective.

To move toward that goal, they say they needed to first test two hypotheses: that their non-toxic combination interventions would work in mice, and that it would look promising for human clinical trials.

In this new study, they said that they've demonstrated both. At least five clinical trials, including one at USC on breast cancer and prostate cancer patients, are now investigating the effects of the fasting-mimicking diets in combination with different cancer-fighting drugs.

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Agencies
February 4,2020

Despite tremendous advances in treatment of congenital heart disease (CHD), a new global study shows that the chances for a child to survive a CHD diagnosis is significantly less in low-income countries.

The research revealed that nearly 12 million people are currently living with CHD globally, 18.7 per cent more than in 1990.

The findings, published in The Lancet, is drawn from the first comprehensive study of congenital heart disease across 195 countries, prepared using data from the Global Burden of Diseases, Injuries and Risk Factors Study 2017 (GBD).

"Previous congenital heart estimates came from few data sources, were geographically narrow and did not evaluate CHD throughout the life course," said the study authors from Children's National Hospital in the US.

This is the first time the GBD study data was used along with all available data sources and previous publications - making it the most comprehensive study on the congenital heart disease burden to date.

The study found a 34.5 per cent decline in deaths from congenital disease between 1990 to 2017. Nearly 70 per cent of deaths caused by CHD in 2017 (180,624) were in infants less than one year old.

Most CHD deaths occurred in countries within the low and low-middle socio-demographic index (SDI) quintiles.

Mortality rates get lower as a country's Socio-demographic Index (SDI) rises, the study said.

According to the researchers, birth prevalence of CHD was not related to a country's socio-demographic status, but overall prevalence was much lower in the poorest countries of the world.

This is because children in these countries do not have access to life saving surgical services, they added.

"In high income countries like the United States, we diagnose some heart conditions prenatally during the 20-week ultrasound," said Gerard Martin from Children's National Hospital who contributed to the study.

"For children born in middle- and low-income countries, these data draw stark attention to what we as cardiologists already knew from our own work in these countries -- the lack of diagnostic and treatment tools leads to lower survival rates for children born with CHD," said researcher Craig Sable.

"The UN has prioritised reduction of premature deaths from heart disease, but to meet the target of 'ending preventable deaths of newborns and children under 5 years of age,' health policy makers will need to develop specific accountability measures that address barriers and improve access to care and treatment," the authors wrote.

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