Obesity Prevention May Be Possible By Controlling Area Of Brain That Produces Sugar and Starch Cravings.

Brain Craving For Glucose Detected

There may be a way to control the area of the brain responsible for craving sugars and carbohydrates.

Inside your brain there’s a special area that drives our cravings for sweet and starchy foods, and researchers have just found the mechanism behind the wheel. The reason we reach for the comforting mashed potatoes and after-dinner cookies could all change if the mechanism could be controlled. Researchers from the Imperial College London studied how glucose, which is found in added sugars but is also the building block of starches, affects the brain. Their published study appears in the Journal of Clinical Investigation.

“Our brains rely heavily on glucose for energy,” the study’s lead author Dr. James Gardiner, from the Department of Medicine, said in a press release. “It’s clearly a very important nutrient, but in our evolutionary past it would have been hard to come by. So we have a deep-rooted preference for glucose-rich foods and seek them out.”

Researchers tracked glucokinase in rats because it’s responsible for detecting glucose in the liver and pancreas. It’s an enzyme also present in the hypothalamus, which is where the brain regulates food intake and sleep. After the rats went 24 hours without eating, glucokinase increased sharply in the hypothalamus. When they were fed normal food and food high in glucose, researchers increased the amount of glucokinase in their hypothalamus, and the rats ate more glucose than normal food. When glucokinase was decreased in their system, they consumed less glucose food.

“This is the first time anyone has discovered a system in the brain that responds to a specific nutrient, rather than energy intake in general,” Gardiner said. “It suggests that when you’re thinking about diet, you have to think about different nutrients, not just count calories.”

By figuring out how to control the newly discovered mechanism involved in glucose cravings, Gardiner suggests humans could then reduce cravings with assistance from a drug. If the mechanism is the key to controlling cravings, Gardiner believes it could potentially prevent obesity, but they need to study how it functions in humans, and then adjust amounts for each person first.

“People are likely to have different levels of this enzyme, so different things will work for different people,” Gardiner said. “For some people, eating more starchy foods at the start of a meal might be a way to feel full more quickly by targeting this system, meaning they eat less overall.”

Source: Gardiner J, Hussain S, Richardson E , Ma Y, Holton C, and Backer ID, et al. Glucokinase activity in the arcuate nucleus regulates glucose intake Journal of Clinical Investigation. 2014.

Don’t want to put on weight as you get older? Try sweet chili peppers and cold spells.

Don’t want to put on weight as you get older? Try sweet chili peppers and cold spells .

Scientists say exposure to moderately cold temperatures and a chemical found in chilies have been shown to boost levels of ‘brown fats’ linked to staving off weight gain.

Scientists have discovered that prolonged exposure to cold temperatures and eating chili peppers can help to prevent people putting on weight as they get older.

In a ground-breaking study from Japan, it has been shown that both cold and a chemical found in the peppers have similar effects in building up levels of BAT (brown adipose tissue), which helps regulate the way the body expends energy.

BAT is a kind of tissue that exists in all babies, found around the neck and chest, but which gradually breaks down as adults get older. This rate varies between people, and previous studies have proven there is a link between BAT levels dropping off and age-related weight-gain setting in.

This is the first time anyone has been able to prove BAT levels can be made to recover once lost. Scientists exposed test subjects to moderately low temperatures, around 17°C, for two hours every day over six weeks.

When compared to a control group that went about their lives as normal, those subjected to cold showed increased levels of BAT – and also lost around 5 per cent of their body fat.

While this might seem a fairly obvious outcome as the test subjects’ bodies work harder to keep warm, what was really surprising was the similar effect on BAT of consuming “capsinoids”, found predominantly in sweet chili peppers.

Capsinoids have been shown to activate temperature sensors in the gut – similar to the way hot-tasting chilies impact sensors in the mouth.

Those studied who ate large quantities of peppers were also seen to experience increases in BAT tissue – though they didn’t, yet, lose body fat. Researchers speculated that a longer study would likely show genuine weight loss to go with the recovery of BAT.

Lead researcher and report author Takeshi Yoneshiro, from the Hokkaido University Graduate School of Medicine in Japan, said: “Our results showed that human BAT could be recruited even in individuals who had lost BAT, thereby contributing to body fat reduction. This is the first report of successful recruitment of BAT leading to reduced body fat in humans.”

He added that capsinoids appear to induce so-called “brown fat” in the same way as cold by “capturing” the same cellular system that the body’s nervous system uses to increase heat production.

Source: Journal of Clinical Investigation.

Vaccine stirs immune activity against advanced, hard-to-treat leukemia.

Novel treatment boosted selective immune attack on leukemia cells in post-transplant patients

Patients with advanced chronic lymphocytic leukemia (CLL) often receive donor transplants that effectively “reboot” their own immune defenses, which then attack and potentially cure the hard-to-treat disease. However, there is a high rate of relapse in these patients, and the transplanted immune cells may also harm normal tissues, causing graft-versus-host disease (GVHD).

Now, scientists at Dana-Farber Cancer Institute report in the
 Journal of Clinical Investigation that they observed a strong and selective immune response in some patients who received, shortly after the transplant, several doses of a “personalized” tumor vaccine composed of their own inactivated leukemia cells combined with an immune stimulant, GM-CSF. Thus the vaccine boosted the power of the transplanted immune system’s ability to attack the cancer – known as the graft-versus-leukemia (GvL) effect.

“Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control” following transplants from donors, saidCatherine Wu, MD, senior author. “Although this was a phase 1 study and not powered to look at questions of clinical efficacy, we did see promising clinical activity.”

There are few treatment options for advanced CLL. Standard transplants, which involve powerful doses of pre-transplant chemotherapy to wipe out as much of the leukemia as possible, have proven too toxic for older patients and those with co-existing diseases. Over the past decade, researchers have developed reduced-intensity conditioning (RIC) regimens, using lower chemotherapy doses that are more tolerable but which rely entirely on the activity of the transplanted immune cells to battle the leukemia. Usually this is insufficient to keep the cancer at bay long-term and the disease progresses.

Furthermore, research has shown that the identifying antigens on the surface of CLL cells in individual patients may differ – that is, they have “personal tumor antigens,” the scientists said. “Based on these principles, vaccination with autologous [the patient’s own stored leukemia cells] irradiated leukemia cells is an attractive approach to expand leukemia-reactive T cells, since this vaccine formulation reliably includes personal tumor antigens.”

To make the vaccine, the researchers mixed the patients’ irradiated leukemia cells with cells that produce GM-CSF (granulocyte-macrophage colony-stimulating factor) and then injected them back into the patient. The combination stirs up a strong response by immune T cells, and the distinctive antigens on the injected leukemia cells direct the T cells to attack similar leukemia cells wherever they are present in the body.

In the phase 1 trial, the vaccine was administered between 30 and 100 days after the transplant, with some patients receiving as many as six vaccine doses. The study enrolled 22 patients with advanced, aggressive CLL. Thirteen of the patients had evidence of the leukemia in their bone marrow at the time of transplant.

Four patients did not receive the vaccine because they developed GVHD following the transplant. The remaining 18 received at least one vaccine dose; seven patients stopped receiving the vaccine after they developed GVHD.

When examined six months post-transplant, the majority of patients showed evidence of clinical response: 10 had complete remissions and six had partial remissions. After a median follow-up of 2.9 years, 13 patients (72 percent) had remained in continuous complete remission; one patient had stable disease, three patients developed progressive disease and two of those patients died.

The results support the safety and biological activity of whole tumor-cell vaccination in hematological malignancies, said the authors, and that giving the vaccine shortly after transplant may have been critical in its effectiveness. In addition, they said a key to the vaccine’s potency was the development by Dana-Farber scientists of GM-CSF-secreting “bystander” cells that can be used against lymphoid malignancies – which was not possible previously.

However, the authors noted that further randomized studies in larger patient groups will be necessary to determine if this strategy “will translate into a true clinical benefit for patients with advanced CLL.”


GM rice delivers antibodies against deadly rotavirus.

A strain of rice genetically engineered to protect against diarrhoeal disease could offer a cost-effective way to protect children in developing countries, according a study published in the Journal of Clinical Investigation today (8 August).

Researchers engineered the rice, called MucoRice-ARP1, by adding an antibody to fight rotavirus originally found in llamas in the rice genome.

Rotavirus is the leading cause of severe diarrhea in young children and infants, killing more than 520,000 people each year, according to the WHO. More than 85 per cent of those deaths occur in impoverished countries in Africa and Asia.

The team fed MucoRice-ARP1 to mice they subsequently infected with rotavirus, and found these mice had significantly less virus than mice fed normal rice.

The rice could be used to complement vaccinations to protect childrenwhen they are at their most vulnerable to rotavirus, say the researchers.

But it had not yet been tested on humans, and could take a decade before a final product is ready for distribution, says one of the study’s authors Yoshikazu Yuki, of the University of Tokyo in Japan.

The WHO has recommended since 2009 that rotavirus vaccines be included in national immunisation programmes.

But studies have since shown that these vaccines are less effective in developing countries than in industrialised countries, protecting only 50–60 per cent of people immunised in developing countries, compared with 85–98 per cent in industrialised countries.

The reasons for the drop in effectiveness are not yet established, but weakened immune systems are a likely factor says Miren Iturriza-Gomara, a virologist at the UK-based University of Liverpool and one of the study’s authors.

MucoRice-ARP1 could complement existing vaccine schedules. It would not be a substitute for a vaccine, she says, “but it’s something that in certain situations could be very helpful”.

For example, the rice could be given to children under two years old when rotavirus infection is most likely to prove fatal.

The research team found that MucoRice-ARP1 is most effective when consumed as a powder diluted with water, although the antibodies could also be ingested either in cooked rice or by drinking the water in which MucoRice-ARP1 is boiled.

Iturriza-Gomara says the rice could also prove useful during rotavirus outbreaks by lowering transmission rates.

“We must ensure that all the currently available tools are made available to every child in the world.”

Mathuram Santosham

Previous clinical trials in Bangladesh have already established that the antibody arp1 can protect against rotavirus.

Originally found in llamas, arp1 is ideal for oral immunotherapy as it is not readily digested by the acids in the human stomach, according to Iturriza-Gomara.

“Llamas produce single-chain antibodies which have two important properties: one, they are very small and can reach areas of the pathogen which otherwise might not be reached by other antibodies and also because they are single-chain they are very resistant,” Iturriza-Gomara says. “Normal human antibodies are dual-chained. If you eat it and it goes through the stomach, the acid will break it and therefore it won’t be active in the intestine which is where you want it.”

MucoRice-ARP1 would have to be eaten regularly to ensure protection.

“Once you have engineered the rice, then it’s just a matter of growing it,” says Iturriza-Gomara. She says the ease of growing rice, and the fact that it is widely produced as a staple food make it a good vehicle for delivering the antibody. “It can also be stored for years without changes in its edibility,” she says.

While the initial results are promising, says Mathuram Santosham, a leading rotavirus researcher at Johns Hopkins University, United States, “substantially more research is needed to understand the potential impact of this intervention in humans”.

“In the meantime, it is important to remember that we have highly effective tools, which are available now, including rotavirus vaccines, oral rehydration solution and zinc supplementation,” Santosham says. “We must ensure that all the currently available tools are made available to every child in the world.”

Source: Scivx

Obesity Gene Linked to Hunger Hormone.

Researchers think they’ve hit on why a common obesity gene causes weight gain: Those who carry a version of it don’t feel full after eating and take in extra calories. That’s because the variant of the FTO gene in question, which one in six individuals carry, leads to higher levels of ghrelin, a hormone involved in mediating appetite and the body’s response to food, researchers have discovered. While most studies on FTO have relied on mice, the new work analyzed blood samples and brain scans from humans.

“This is a very exciting piece of research,” says geneticist Andrew Hattersley of the Peninsula Medical School in Exeter, U.K., who was not involved in the new study. “There is a lot of work that’s been done on the mechanism of FTO in animals, but you have to be careful about applying those lessons to people. So it’s nice to finally see work done in humans.”

Hattersley was part of a team that in 2007 reported that people who had one version of the FTO gene, called AA, weighed an average of 3 kilograms more than those with the TT version of the gene. Since then, studies in mice have shown that in everyone, there are high levels of the FTO protein in brain areas that control energy balance. Researchers have also found that animals with the AA version tend to eat more and prefer high-fat food compared with those with the TT version. But why FTO had this effect wasn’t known.

Rachel Batterham, an endocrine and obesity researcher at University College London, thought that gut hormones that mediate the body’s response to eating could be the missing link between FTO and food intake. One such hormone is ghrelin, known to be produced by gut cells to stimulate hunger. So Batterham and her colleagues measured levels of ghrelin in the blood of nonobese men with the AA or TT versions of FTO. In those with the TT variant, ghrelin levels rose before a meal, when the person experienced hunger, and fell after eating, as expected. But in those with the obesity-associated AA version, ghrelin levels stayed relatively high even after eating. Moreover, the AA individuals reported a faster increase in hunger after a test meal. And MRI scans revealed that, when the test subjects were shown images of food before or after eating, brain activity in areas associated with motivation and rewards remained high before and after the meal in AA individuals. This suggests that the increased ghrelin levels were impacting the brain’s response to food—which “fits very well with what we already know the effects of ghrelin,” Batterham says.

But could higher ghrelin levels be unrelated to FTO? The researchers don’t think so, in part because they found that in isolated human cells, increased levels of FTO protein led to more ghrelin production. The reason this happens, the group showed, is because that the FTO protein actually alters the ghrelin gene, causing methyl chemical groups to be removed, a so-called epigenetic modification that impacts how much protein the ghrelin gene produces. The AA gene variant, the researchers report online today in The Journal of Clinical Investigation, removed more methyl groups from the gene, leading to increased levels of the hunger hormone.

Whether that proves true, the full story is FTO remains to be uncovered, Hattersley says. “What we don’t know is whether FTO is changing many things that alter appetite, of which ghrelin is just one,” he says. “I suspect human appetite and obesity is more complex than a single hormone.”

Neurobiologist Tamas Horvath of Yale University agrees. “This is a beautiful piece of work at face value,” he says. “But I think it’s reasonable to continue pursuing many other avenues to see what else might be going on here.”

Source: sciencemag.org



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