Slimming pill that ‘tells’ your brain you are full

The weight-loss drug contains leptin, a hormone the body naturally uses to signal that it is full.

Developing the pill will be a ‘great contribution to public health’ in the fight to tackle obesity, say researchers.
The finding is based on research on mammals, whose bodies use leptin as an appetite regulator, they added.

‘Mice deprived of leptin will not stop eating. They become so big they have trouble moving around,’ said study author Prof Moose Bendayan of Montreal University.

It has been proven to be an appetite suppressant when injected but the latest development would see it taken orally.

Obesity ups cancer risk

Obesity increases risk of developing cancer. And now, a mice study has confirmed that obesity does indeed act as a "bona fide tumour promoter."

Published in the January 22nd issue of the journal Cell , a Cell Press publication , scientists also have good evidence to explain how that happens.

"Doctors always worry about our weight, but the focus is often on cardiovascular disease and type 2 diabetes, both of which can be managed pretty well with existing drugs," said Michael Karin of the University of California, San Diego. "However, we should also worry about elevated cancer risk. If we can reduce cancer deaths by as many as 90,000 per year, that’s a lot of people – a lot of lives."

In the study, Karin’s team showed that liver cancer is fostered by the chronic inflammatory state that goes with obesity and two well known inflammatory factors in particular.

To reach the conclusion, Karin’s team investigated mice prone to develop hepatocellular carcinoma (HCC).

The mice are typically given HCC either by exposure to a chemical carcinogen, known as DEN, when they are two weeks old, or by exposure to that same carcinogen at three months of age followed by the tumor-promoting chemical phenobarbitol.

In the new study, the researchers gave two-week-old mice DEN and then divided them into two groups – one fed a normal, relatively low-fat food and the other fed on high-fat chow.

"It was clear that the mice on the high fat diet developed more liver cancer," Karin said...

The Fatter You Are – The More the Risk of Cancer

Obesity is usually believed by the doctors to be leading to the cardiovascular problems, commonly known as the problems relating to the heart, and secondly towards the problem of diabetes, popularly known as the sugar problem. But so far nobody had thought that the obesity or the fatness of the body could lead you to the problem of your getting cancer.

More the fat you add to your body, the more prone you become to the fatal disease of cancer, says a study conducted under the supervision of distinguished Professor Michael Karin, PhD, Department of Pharmacology, University of California, San Diego (UCSD). The study was conducted on the mice and Prof. Karin deserves the thanks from the core of our hearts for forewarning the people suffering from obesity. The results of the study have been published in the “Cell” journal in its issue of Friday, 22nd January, 2010.

The study reveals that with the excess fat in the body, your body becomes prone to the creation and growth of cancer cells so much so that those who are having excess fat in the liver are 4.5 times more prone to the liver cancer and those who are otherwise having obesity, they are prone to other types of cancer by 1.5 fold. The study further adds that about 90,000 lives could be saved per year, if the obesity is brought under control...

ROTEIN MAY BE NEW TARGET FOR OBESITY, DIABETES THERAPIES

A little bit of stress might be just what the doctor ordered to combat obesity and diabetes.

A new study in mice finds that a protein that plays a role in responding to certain kinds of stress may help regulate a metabolic pathway important for controlling blood sugar, burning fat and even making tumors grow. The study shows that the protein, known to play a role in aging (SN: 1/31/09, p. 13), is part of a protein family that has its finger on the pulse of both major pathways cells use to make energy, says Leonard Guarente, a molecular biologist at MIT who was not involved in the research.

The study indicates that the protein, known as sirtuin 6, or SIRT6, is what’s known as a master regulator, in this case helping cells switch between oxidative metabolism, the major form of energy production in cells; and anaerobic glycolysis, a less efficient way of making energy and can be tapped when oxygen or nutrients are in short supply. The anaerobic form of glycolysis needs more glucose to generate the same amount of energy as oxidative processes. The study, which appears in the Jan. 22 Cell, could lead the way to new therapies for diabetes and obesity...

Mice that lack SIRT6 seem normal at birth but die a few weeks later of hypoglycemia, or low blood sugar. No one knew how absence of the sirtuin protein could affect blood sugar levels so dramatically, says Raul Mostoslavsky, a molecular biologist at Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. In the new study, Mostoslavsky and his colleagues show that SIRT6 works with a stress-response protein known as Hif1alpha to control when and whether cells switch to anaerobic glycolysis...

When SIRT6 is missing or not working correctly, Hif1alpha inappropriately turns on anaerobic glycolysis and, the researchers found, turns off mitochondria, the cellular power plants where oxidative metabolism takes place.

That explains why mice missing SIRT6 become hypoglycemic, Mostoslavsky says. The animals burn all of their glucose trying to make enough energy to stay alive. For the first 10 to 12 days of life, these mice manage, but eventually the animals burn through all of their reserves, including fat stores, and die.

“Since the mice are using glucose for glycolysis, they are burning fat like crazy,” Mostoslavsky says.

Mostoslavsky suggests that drugs could be designed to turn down SIRT6 activity slightly. Targeting the protein might help diabetics lower blood sugar by burning that extra sugar for energy. And obese people might be able to lose weight by turning excess fat into energy the way SIRT6 mutant mice do...

FATTY DIET MAKES CANCER AGGRESSIVE

Obesity, or a diet high in fats, can kick-start a benign tumor into life-threatening cancer, according to new research published in the journal Cell.

In the study, scientists from Scripps Research Institute found a new enzyme, known as MAGL, that human cancer cells use to turn fat into a signaling molecule, essentially talking itself into growing larger and more dangerous.

The research means that patients recently diagnosed with cancer could be prescribed a diet low in fat to slow the growth of the cancer, also helps explain the link between cancer and obesity.

"The implication of this study are that a person with an aggressive cancer, if they are eating a diet high in fat or are obese, could exacerbate the cancer's growth," said Daniel Nomura, a co-author of the study.

Scientists have known that obesity is linked with higher rates of pancreatic, breast, kidney, esophageal, and other cancers cancers for years. Why obesity and cancer are linked is still largely a mystery, however. Various factors, such as increased acid reflux to insulin levels, explain some of the data for specific cancers, but no general, all-encompassing model linking the two has been found.

The new study doesn't completely explain the link between cancer and obesity, says Nomura, but it gives yet another explanation for the link.

The body uses fat to store excess energy that it cannot use right away. When a person works out, the body taps into those stores of fat to provide energy for, say, running legs or weight-lifting arms.

Physical exercise helps brains grow, mouse study

Fresh research may help explain why regular exercise can improve brain power, say Cambridge scientists.

The report, which was published in the Proceedings of the National Academy of Sciences, found mice which exercised performed better on memory tests.

These mice also grew more new cells in a part of the brain linked to memory than those which did not exercise.
The authors believe the new brain cells were behind the improvement in cognitive performance.

Link Between Leptin And Blood Sugar Could Pave Way For A Potential Cure For Diabetes

The relationship between obesity and diabetes has intrigued scientists for ages. While research corroborated a definitive link between obesity and diabetes, the exact reason between obesity and diabetes is still being understood. A study conducted by researchers at the University of Michigan and Harvard University report new evidence in mice that may help explain that link — and may help them understand why some obese people never develop diabetes while many others do...

Extensive proteomic screening identifies the obesity-related NYGGF4 protein as a novel LRP-interactor, showing reduced expression in early Alzheimer's

The low-density lipoprotein receptor related protein 1 (LRP1) has been implicated in Alzheimer's disease (AD) but its signalling has not been fully evaluated. There is good evidence that the cytoplasmic domain of LRP1 is involved in protein-protein interactions, important in the cell biology of LRP1.

Results: We carried out three yeast two-hybrid screens to identify proteins that interact with the cytoplasmic domain of LRP1.

The screens included both conventional screens as well as a novel, split-ubiquitin-based screen in which an LRP1 construct was expressed and screened as a transmembrane protein. The split-ubiquitin screen was validated in a screen using full-length amyloid protein precursor (APP), which successfully identified FE65 and FE65L2, as well as novel interactors (Rab3a, Napg, and ubiquitin b).

Using both a conventional screen as well as the split-ubiquitin screen, we identified NYGGF4 as a novel LRP1 interactor. The interaction between LRP1 and NYGGF4 was validated using two-hybrid assays, coprecipitation and colocalization in mammalian cells.

Mutation analysis demonstrated a specific interaction of NYGGF4 with an NPXY motif that required an intact tyrosine residue. Interestingly, while we confirmed that other LRP1 interactors we identified, including JIP1B and EB-1, were also able to bind to APP, NYGGF4 was unique in that it showed specific binding with LRP1.

Expression of NYGGF4 decreased significantly in patients with AD as compared to age-matched controls, and showed decreasing expression with AD disease progression. Examination of Nyggf4 expression in mice with different alleles of the human APOE4 gene showed significant differences in Nyggf4 expression.

Conclusions: These results implicate NYGGF4 as a novel and specific interactor of LRP1.

Decreased expression of LRP1 and NYGGF4 over disease, evident with the presence of even moderate numbers of neuritic plaques, suggests that LRP1-NYGGF4 is a system altered early in disease. Genetic and functional studies have implicated both LRP1 and NYGGF4 in obesity and cardiovascular disease and the physical association of these proteins may reflect a common mechanism...

The path to fat yields endurance

U.S. researchers say staying lean on a high-fat diet is possible, but at the cost of reduced endurance.

Study senior author Dr. Leonid Zingman of the University of Iowa in Iowa City says mouse studies show the molecular pathway leading to fat deposition -- the ATP-sensitive potassium channel -- is also key to survival and stress adaptation.

Zingman and colleagues found mice genetically altered to bypass this pathway did in fact, develop obesity resistance.

"Indeed, disrupting the channel made the mice burn more calories even while at rest and also made them less fuel efficient when exercising, and therefore less capable of maintaining physical performance," Zingman says in a statement...

Potassium Channels in Muscles May Offer Obesity Target

Targeting a mechanism involved in energy expenditure in muscles may help treat obesity, according to research published in the Jan. 6 issue of Cell Metabolism.

Alexey E. Alekseev, Ph.D., of the Mayo Clinic in Rochester, Minn., and colleagues analyzed data from KATP channel-deficient mice. These ATP-sensitive potassium channels play a role in regulating cardiac and skeletal muscle action potentials.

The researchers found that mature knockout mice lacking the KATP channels demonstrated lower body weight and fat storage than wild-type mice, but grew to a similar length. Evidence suggested that knockout mice had greater energy expenditure and a higher rate of carbohydrate consumption. These mice also were resistant to becoming obese while on a high-fat diet, compared to wild-type mice, which did become obese. However, the knockout mice also had decreased workload endurance...

Blueberry Drink Protects Mice from Diabetes, Obesity

A special blueberry drink fortified by processing it with bacteria that naturally occur on the fruit's skin proved effective at preventing the development of obesity and diabetes in mice predisposed to the conditions, in a study conducted by researchers from the University of Montreal, the Institut Armand-Frappier and the Université de Moncton, and published in the International Journal of Obesity.

Researchers "biotransformed" juice from the North American lowbush blueberry by fermenting it with Serratia vaccinii, a bacteria naturally found on the berry's skin. They then fed mice either the biotransformed juice or unmodified blueberry juice for three days. All the mice had been bred for resistance to the hormone leptin, thus predisposing them to obesity, insulin resistance, diabetes and high blood pressure

"Consumption of fermented blueberry juice gradually and significantly reduced high blood glucose levels in diabetic mice," lead author Tri Vuong said. "After three days, our mice subjects reduced their glycemia levels by 35 percent."...

Scientists look to control obesity by burning more calories

"New research by scientists from the Mayo Clinic and the University of Iowa suggests that obesity may be kept under check by increasing the number of calories burnt by muscles.

Researchers experimented on mice to explore the 'fuel gauge' in muscles and found new evidence that treatments done to disrupt the sarcolemmal ATP-sensitive K+ (KATP) channels in muscles may help to limit obesity."

Austrian scientists curb obesity in mice by modifying ‘hedgehog’ gene

"Scientists from Austrian Academy of Sciences, Institute for Molecular Biotechnology (IMBA) and Institute of Molecular Pathology at Austria's University of Salzburg have discovered that gene therapy can play a notable role in slowing down the formation of unwanted fat in the body, by suppressing the growth of white fat cells.

Noting that the intervention effect of gene on fat formation was too substantial to be overlooked, the molecular biologists said in the new study, published in the US scientific journal Cell, that experiments with mice have revealed that the modification of a certain gene - 'Hedgehog' - helped raise very lean, but otherwise healthy, animals that developed almost no white fat cells.

Since the white fat cells serve chiefly in storage of body fat, the Austrian scientists, together with the scientists from University of Toronto, Canada, were able to curb the growth of white fat by purposefully stimulating the 'hedgehog' gene in the mice experiments.

With the therapy having successfully cut down obesity in mice, by unlocking the genetic mechanism, the researchers are of the opinion that their research will have 'a very impressive prospect for medical applications.'"

Cellular Tweak Helps Mice Burn More Fat

"A molecular mechanism that controls energy expenditure in muscles and helps determine body weight has been identified by U.S. researchers, who said their finding could lead to a new way to treat obesity.

In experiments with mice, the scientists found that energy expenditure is controlled by the ATP-sensitive potassium (KATP) channel. ATP (adenosine triphosphate) is the "energy currency" used by cells. The KATP channel can sense ATP pools and make appropriate adjustments to heart and skeletal performance, the researchers noted.

Mice that lack the KATP channel burn more stored energy through the dissipation of heat at normal activity levels or when resting, according to the report in the Jan. 6 edition of the journal Cell Metabolism."

Setting the Record Straight on Weight Loss

"It's time to set the record straight. The only reliable way to lose weight is to eat less or exercise more. Preferably both

So why bother to state the obvious? Because a body of scientific literature has arisen over recent years, suggesting that fat oxidation -- burning the fats we eat as opposed to the carbohydrates -- is enough to promote fat loss. It isn't.

Sydney scientists have demonstrated that mice genetically altered to burn fats in preference to carbohydrates, will convert the unburned carbohydrates into stored fat anyway, and their ultimate weight and body composition will be the same as normal mice."

New Epigenetic Study Shows A Link Between Maternal Diet And Brain Development In Gestating Mice

"If you're pregnant and looking for an excuse to eat bacon and eggs, now you've got one: a new research study published in the January 2010 print issue of the FASEB Journal by a team of University of North Carolina researchers shows that choline plays a critical role in helping fetal brains develop regions associated with memory. Choline is found in meats, including pork, as well as chicken eggs."

Is there an obesity virus?

"If New Year dawned to the vision of a continuing obesity epidemic in your bathroom mirror, you will no doubt have already resolved - once again – to regain svelteness by the well known "calories in, calories out" equation – eat less, move more. Regular exercise and a balanced diet are, of course, the cornerstones of achieving a healthy weight. Yet some obesity specialists are now convinced that the cause of the Western world's expanding waistlines is rather more complex – and that there are additional factors to blame for unwanted weight gain. Here are some of them...

Room temperature

Scientists have shown that mice living in cosily warm cages are fatter than those lodging in more extreme temperatures – hot or cold. And the same may go for humans. A recent study by the American National Center for Healthy Housing found that the rise in obesity in the USA correlates with the increase in central heating and air conditioning in homes and offices. It seems unlikely that this research will result in widespread abandonment of either of these moderating influences. But it does underline useful weight loss strategies, says Carole Caplin. 'When you're hot and sweating, you're eliminating fluid retention – as well as stored toxins - rather than burning calories,' she says. 'That's why a steam or sauna is both healthy and promotes weight loss. When you're uncomfortably cold, on the other hand, your body works harder, burning fat to get warm. Cycling, brisk walks or playing any sport in cold weather is a way to feel good and burn calories.'"

Lose Sleep, Gain Weight: Another Piece of the Obesity Puzzle

"It’s 11 P.M., and you sit in front of a glowing computer screen, writing e-mails and eating a sandwich. You’ll work until after midnight, when you’ll fall asleep in front of the light and blare of a TV before rising again at 6 A.M. What’s wrong with this picture? Because of modern conveniences and pressures, many of us keep our bodies exposed to light, food, and activity at times when our organs and cells expect dark, quiet, and sleep.

In epidemiologic studies, shorter sleep has been correlated with incidence of obesity, hypertension, and other metabolic disorders. Experimental sleep studies find a similar connection. Increasingly, studies of the possible mechanisms behind these associations suggest that lack of sleep is part of a bigger problem with the 24/7 lifestyle many people today lead. Increasingly, scientists are finding that many physiologic activities

related to metabolism don’t happen continuously but oscillate on a regular schedule. Studies in mice as well as humans suggest that when our internal clock is disrupted, it may throw off many bodily functions, especially metabolism."

US team may have found key to fight obesity: study

"Shutting down an energy-controlling mechanism in mice left them leaner than normal mice and could be a new way to fight obesity in humans, US researchers said.

And the finding is big news in the United States, where around a third of the adult population is considered obese, meaning they have a body mass index (BMI) greater than 30, according to the American Obesity Association.
BMI is calculated by dividing a person's body weight in kilograms by their height in meters squared.

The researchers found that by switching off potassium channels which are sensitive to adenosine triphosphate (ATP) -- a molecule in cells that stores the energy we need to do just about everything -- made mice burn more energy and left them leaner than normal mice.

The effect was evident even when the mice were fed high-fat 'Western' diets and was long-lasting, too, with the mice remaining slim throughout their lives, scientists from the Mayo Clinic, University of Iowa, University of Connecticut and New York University reported in the journal Cell Metabolism...

One finding was that mice in whom the KATP channel had been switched off burned more glycogen -- the form in which carbohydrates are stored in the body and the primary source of energy for endurance athletes -- and stored body fat than ordinary mice.

That means that achieving greater leanness by deactivating KATP channels comes at the cost of reduced endurance."

High Fat Diet Increases Inflammation in the Mouse Colon

"Colorectal cancer, the third most common type of cancer worldwide, has been linked to an increased prevalence of the Western diet: one high in fat and low in fiber, vitamin D and calcium. Now, a team of scientists led by researchers at Rockefeller University have shown what happens to colon tissue when mice are fed such a diet: an inflammatory response that could be the trigger for carcinogenic processes. Their results are published in the November 2009 issue of The Journal of Nutrition...

The researchers fed experimental mice either a standard diet containing five percent fat and ample amounts of calcium and vitamin D or a Western diet containing 20 percent fat and adequate but marginal levels of calcium and vitamin D for three or six months.

As expected, animals consuming the Western diet were heavier and had more fat tissue than those on the control diet."