Manipulating Molecules in Heart Protects Mice On High-Fat Diets from Obesity, Affects Metabolism

UT Southwestern Medical Center researchers have demonstrated for the first time that the heart can regulate energy balance throughout the body, a finding that may point to more effective treatments for obesity, diabetes, and heart disease. Obesity, cardiovascular disease, and diabetes affect tens of millions of people in the U.S., according to the Centers for Disease Control and Prevention. Using mice fed a high-fat diet, researchers found that manipulating a heart-specific genetic pathway prevents obesity and protects against harmful blood-sugar changes associated with type 2 diabetes...more

Fat gene may predict protection against diabetes, study suggests

While obesity is a huge risk factor for type 2 diabetes, many people with 50 or 60 extra pounds to lose never develop the condition, and a new study from Beth Israel Deaconess Medical Center provides a possible explanation. It may have something to do with how much they express a particular gene in their fat cells; the gene makes cells more sensitive to the hormone insulin which transports glucose into cells. Normally, type 2 diabetes occurs when cells become resistant to insulin, causing blood sugar levels to rise to dangerously high levels. In the study published Sunday in the journal Nature, the researchers manipulated the “glucose transporter” gene in obese mice to allow more sugar into fat cells and found that the mice didn’t develop diabetes. On the flip side, normal weight mice who lacked the glucose transporter gene had soaring blood sugar levels. “We all have this gene but how much it’s turned on and expressed in our fat cells seems to be predictive of how metabolically healthy we are,” explained study co-author Dr. Barbara Kahn, an endocrinologist at Beth Israel Deaconess Medical Center. Those with high levels of expression get more protection from diabetes, while those with low levels have less protection...

New lab mice cut search for genetic links to disease by more than a decade

With a 95 percent genomic similarity to humans, mice have long been used to learn about the genetic causes of human disease. Once researchers can shine a light on the genetic factors that cause disease in mice, they can start to develop prevention and treatment options to protect the human population. But this process, called genetic mapping, is a long and difficult road, made more challenging by the 5% difference between the humans and lab mice. Now Prof. Fuad Iraqi of Tel Aviv University's Sackler Faculty of Medicine is closing the gap with an international project called Collaborative Cross. The project is developing lab mice with increased genetic diversity, making them more advantageous for genetic research related to human health. The new population will offer 1,000 genetic strains within a fixed genotype — the composite of the entire genetic makeup of an organism. This is a marked improvement on the previously existing 450 genetic strains of lab mice with varying genotypes, making Prof. Iraqi's new strain ideal for genetic mapping. And with these mice, researchers will be able to identify a gene associated with a particular disease within two to three years instead of the 10 to 15 years it takes now, says Prof. Iraqi...

Biologist claims certain chemicals increase chance of obesity

Obesity is at epidemic proportions in this country. But what if some people are overweight, not only because of the brownies they eat, but because of the plastic containers they store them in? The conventional theory goes that people become obese because they take in more calories than they burn off. But molecular biologist Bruce Blumberg says it’s more complicated than that. "If it were a simple problem, a matter of balancing our caloric checkbook, no one would be fat," says Blumberg. "We are not a country full of lazy people who just eat everything in sight." In his lab at UC Irvine, some of his mice are obese. Blumberg made them that way, but not by overfeeding them. "My mice become fatter on a normal diet," Blumberg explains. "That’s only because they were exposed to this chemical in the womb." The chemical he’s talking about is called Tributyltin. It’s used to preserve wood and is found in some vinyl products. There are more than a dozen kinds of drugs and chemicals that make lab animals — or people — fat. Blumberg calls them obesogens...

Fat mice provide genetic clues to obesity puzzle

A new study published in Nature Medicine provides clues as to how a gene mutation may lead to obesity. Mutations in the brain-derived neurotrophic factor gene (BDNF) have previously been shown to cause obesity in mice and have been identified in severely obese children. Genome-wide association studies have also confirmed BDNF as a susceptibility gene for common obesity in humans. The study investigated the mechanism by which BDNF mutations lead to obesity. Obesity is caused by an excess of energy, which can result from high energy intake, low energy expenditure, or both. Obesity was caused solely by overeating in mice with BDNF mutations, which consumed up to 80% more food than those without the mutation (‘wild type’ mice). When the mice with the mutation were restricted to the amount of food that that the wild type mice chose to eat, they did not become obese...

Study has shown to reverse obesity, body fat and improve insulin sensitivity in mice

Scientists used the ACE inhibitor captopril (CAP)—commonly used for the treatment of hypertension and cardiac conditions—and found that it can reduce the body weight of mice maintained on a high-fat diet. Initially, mice were put on a high fat diet for 12 weeks to produce mice with diet-induced obesity. During the subsequent 12 weeks treatment period, the mice were allowed access to the high-fat diet and either water containing CAP or plain tap water (the control). "From the first week of treatment, food intake and body weight decreased in the mice treated with CAP compared with the control mice. "Both peripheral insulin sensitivity and hepatic insulin sensitivity were improved in CAP treated mice compared with the control, which means there was an improvement in the handling of blood sugar," says Dr. Shirmila Premaratna, lead researcher from the La Trobe’s Faculty of Science, Technology and Engineering...

Skinny genes – how GM food may help you stave off obesity

Fond of a full English breakfast? Perhaps you should have a glass of blood orange juice on the side – it might help to reduce the harm from all the fat you are ingesting, and make you less likely to become obese.

But as blood oranges are among the least favoured fruits for consumers, scientists in the UK are hoping to find ways to genetically modify standard oranges to incorporate the beneficial effects of their less popular cousins.

The project is one of several aimed at improving health through the genetic modification of plants – a process that scientists say could be a low-cost answer to harmful nutritional deficiencies.

Another project involves incorporating algae genes into oilseed rape, in order to produce nutritionally vital fish oils without having to kill fish; and grains modified to take up more zinc from the environment, to alleviate the zinc deficiency that blights millions.

The scientists involved believe that the public will be more accepting of GM plants that plug common nutritional gaps, than those crops that benefit big companies. "This isn't about increasing the profits from multinationals – there are big gains to be had," said Prof Dale Sanders, director of the John Innes Centre, an independent centre for plant science and microbiology research.

Although only a handful of GM experiments are licensed in the UK at present, some lab research continues, although scientists are concerned that the science is moving elsewhere. Cathie Martin, also of the John Innes Centre, who is leading the research on blood oranges, said: "There are enormous problems in creating something that can be grown in Europe, and big problems in public funding, because of the regulation."

Unpublished research has suggested that compounds found within blood oranges could help to cut obesity by reducing the accumulation of fats, and so avoid some of the harm from fatty foods. In one human study, people fed a full English breakfast along with the juice of three blood oranges experienced less accumulation of fat, possibly because of substances known as anthocyanins, found in abundance in blood oranges.

The results should be taken with caution – they are unpublished and have not yet been peer-reviewed. Studies on mice have shown a similar effect, preventing obesity in mice fed a high-fat diet, compared to mice given ordinary orange juice, or water, but the human effects are still uncertain...

'Gluttony gene' stops mice feeling full

A mutation in a gene linked to obesity causes mice to eat up to 80 percent more than normal, a study suggests.

After eating, hormones send signals to the brain to let it know it's full. However, scientists found that in mice with a faulty version of the BDNF gene, these messages were 'blocked'.

'If there is a problem with the BDNF gene, neurons can't talk to each other, and the leptin and insulin [hormone] signals are ineffective, and appetite is not modified', said researcher Professor Baoji Xu from the Georgetown Medical Centre in the USA.

When the team monitored the eating habits of mice with and without the mutation, they found males were twice as heavy as their normal counterparts, and females were 2.7 times heavier. This was to do with them over-eating, rather than a reduction in their activity levels...

New neurons, a recipe for obesity?

An elusive metabolic 'switch' that significantly decreases weight-gain and increases energy consumption in mice, even when fed a high-fat diet, has been uncovered.

If a similar mechanism is found in humans, these findings, published in Nature Neuroscience today, may present a new target for potential treatments aimed at combating diet-induced weight gain and obesity.

"We've identified a region within the mouse hypothalamus in which new neurons are generated in both the postnatal and adult period. Neurogenesis in this area is stimulated by a high-fat diet, and blocking neurogenesis in this region attenuated weight gain on high fat diet," said lead author Seth Blackshaw from the Solomon H. Snyder Department of Neuroscience at Johns Hopkins University in the U.S...

Fat gene linked to diabetes battle

A fat gene has been identified that appears to protect against diabetes.

The discovery suggests that, contrary to popular belief, fatty adipose tissue can benefit the body's metabolism.

Research shows how the gene, ChREBP, resists diabetes by converting glucose sugar into fatty acids. It also boosts sensitivity to insulin, the vital hormone that regulates blood sugar.

However, in most obese people, sugar is blocked from entering fat cells and blood sugar levels rise.

Eventually, this leads to insulin resistance and type-2 diabetes.

Scientists believe the findings could lead to new treatments for diabetes and other metabolic diseases.

They add to previous research based on 123 fat samples from non-diabetic people which showed the gene was more active in those whose bodies had a better sugar balance.

The fat gene's activity also correlated with insulin sensitivity in obese, non-diabetic people.

'The general concept of fat as all bad is not true,' said lead investigator Dr Mark Herman from Harvard Medical School in the US.

'Obesity is commonly associated with metabolic dysfunction that puts people at higher risk for diabetes, stroke and heart disease but there is a large percentage of obese people who are metabolically healthy.

'We started with a mouse model that disassociates obesity from its adverse effects.'...

Beer may improve health of obese people?

Hops compounds improve health of obese diabetic mice
A class of compounds found in hops, the crop generally known for its role in beer production, reduces weight gain in obese and diabetic mice, according to a study published Mar. 28 in the open access journal PLoS ONE. Eight weeks of treatment with the compounds, called tetrahydro iso-alpha acids, also reduced gut permeability and normalized insulin sensitivity markers in the mice, among other beneficial metabolic effects.

Hops have been known to contain anti-inflammatory compounds with potential medicinal uses for metabolic disorders, like insulin resistance and type 2 diabetes, which are associated with low-grade inflammation. These new results suggest a novel mechanism contributing to the positive effects of the investigated treatment, the authors write. The work was led by Patrice Cani of the Université catholique de Louvain in Brussels, Belgium.

Are antibiotics making you fat?

Listen to any TV commercial for a new drug and you'll hear a litany of bizarre side effects — amnesia, hallucinations, nightmares, blue urine and a furry-feeling tongue, just to name a few. But few of these lists include obesity, and overdosing on antibiotics, according to an article published in the magazine New Scientist, could be a major trigger for obesity.

People who overuse antibiotics have lower levels of good bacteria in their guts, and those good bacteria have been found to help prevent everything from cancer to obesity. A number of studies on mice have found that mice fed antibiotics at levels comparable to those given to farm animals are much heavier than mice fed no antibiotics at all — which isn't surprising, considering that antibiotics are often used to speed growth and fatten up animals for slaughter.

But what is concerning are the studies of antibiotics fed to mice at levels similar to what children receive when they get infections. In one study, microbiologist Martin Blaser, of New York University, fed mice short courses of antibiotics similar to those that children receive. Compared to the non-drugged mice, the antibiotic-fed mice had lower levels of T-cells, which regulate the body's immune response. Obesity has been associated with low levels of these T-cells...

Compounds Created That Dramatically Alter Biological Clock And Lead To Weight Loss, Metabolic Changes

Scientists from the Florida campus of The Scripps Research Institute have synthesized a pair of small molecules that dramatically alter the core biological clock in animal models, highlighting the compounds' potential effectiveness in treating a remarkable range of disorders-including obesity, diabetes, high cholesterol, and serious sleep disorders.

The study was published on March 29, 2012, in an advance, online edition of the journal Nature.

The study showed that when administered in animal models the synthetic small molecules altered circadian rhythm and the pattern of core clock gene expression in the brain's hypothalamus, the site of the master cellular clock that synchronizes daily rhythms in mammals; circadian rhythms are the physiological processes that respond to a 24-hour cycle of light and dark and are present in most living things.

When given to diet-induced obese mice, these same small molecules decreased obesity by reducing fat mass and markedly improving cholesterol levels and hyperglycemia - chronically high blood sugar levels that frequently lead to diabetes...