‘Imaginary meal’ in a pill could be new dieting aid

Some obese individuals struggle to lose weight by following a healthy diet and regular exercise alone, which is why many turn to diet pills for a helping hand. In a new study, researchers from the Salk Institute for Biological Studies in La Jolla, CA, detail the creation of a novel diet pill that tricks the body into losing weight, potentially making it more effective than existing diet pills and likely to cause fewer side effects. Ronald Evans, director of the Gene Expression Laboratory at Salk, says the new diet pill – called fexaramine – acts like an “imaginary meal.” “It sends out the same signals that normally happen when you eat a lot of food, so the body starts clearing out space toweightloss-pic-vitatious store it. But there are no calories and no change in appetite,” he explains. When tested in obese mice, fexaramine was found to trigger fat loss, prevent weight gain, control blood sugar and reduce cholesterol and inflammation.

Evans and colleagues recently published their findings in the journal Nature Medicine. Fexaramine targets the body’s farensoid X receptor (FXR) – a protein that is involved in food digestion, fat and sugar storage and the release of bile acids from the liver. The researchers explain that when we start eating a meal, FXR is activated in preparation for food intake. Past studies from Evans and team have indicated that as well as triggering the release of bile acids to aid digestion, FXR alters blood sugar levels and switches on a fat-burning process. Some existing diet pills activate an array of pathways controlled by FXR – including the intestines, liver, kidneys and adrenal glands. Fexaramine, however, only activates the FXR pathway linked to the intestines. When taken orally, the diet pill is only absorbed in the gut and does not enter the bloodstream, meaning it is unlikely to cause the side effects typically associated with existing diet pills – such as high blood pressure, dizziness, insomnia and even heart disease. What is more, the fact that fexaramine only acts in the intestines means it is a more effective weight loss aid, according to the researchers, as the drug is not transported throughout the entire body.

Body’s response to a meal is like a relay race; we’ve learned how to trigger the first runner’ To test the effectiveness of fexaramine, Evans and colleagues gave obese mice a daily dose of the drug for 5 weeks and compared the outcomes with mice that remained untreated. The mice given fexaramine stopped gaining weight and saw a reduction in body fat, blood sugar and cholesterol. What is more, the body temperature of the treated mice increased, indicating a heightened metabolism, and some of the rodent’s white fat deposits were converted into healthier, energy-burning fats. The team says they also saw a change in the assortment of bacteria in the gut, but they note that they are unclear on what this indicates at present. Evans says fexaramine is more effective than diet pills that trigger numerous FXR pathways because it activates the mechanisms by which the body naturally responds to a meal. He explains: “When you eat, you have to quickly activate a series of responses all throughout the body. And the reality is that the very first responder for all this is the intestine. The body’s response to a meal is like a relay race, and if you tell all the runners to go at the same time, you’ll never pass the baton.

We’ve learned how to trigger the first runner so that the rest of the events happen in a natural order.”   Obesity is a major problem in the US, affecting more than a third of adults. Evans and colleagues believe fexaramine is a promising candidate to reduce obesity and the risk of its related diseases – such as type 2 diabetes – in humans. They hope the drug would be used alongside diet and lifestyle changes under the guidance of health care professionals. The team is now in the process of setting up clinical trials to assess the effectiveness of fexaramine in humans.

Metabolic syndrome linked to increased risk of endometrial cancer

Older women with metabolic syndrome may be at increased risk of endometrial cancer, regardless of whether they are overweight or obese. This is according to a new study published in the journal Cancer Epidemiology, Biomarkers & Prevention.

Metabolic syndrome is when an individual has a cluster of factors associated with increased risk of cardiovascular problems and other health conditions. These factors include abdominal obesity, high blood pressure, high cholesterol and abnormal fasting glucose. Around 34% of adults in the US have metabolic syndrome, meaning they are at increased risk of cardiovascular disease, stroke, diabetes and other metabolic-related diseases, compared with the general population. Obesity is considered a major risk factor for endometrialcancer – a form of cancer then begins in the inner lining of the uterus, called the endometrium. In the US, endometrial cancer is the most common cancer of the female reproductive organs; around 1 in 37 women will be diagnosed with the disease in their lifetime.

Past research has indicated that metabolic syndrome may also increase the risk of endometrial cancer. But according to the investigators of this latest study – including Britton Trabert, PhD, of the Division of Cancer Epidemiology and Genetics at the National Institutes of Health – it was unclear as to whether this association was down to obesity or other factors of metabolic syndrome. Metabolic syndrome increased endometrial cancer risk by 17-21%, independent of obesityWith a view to finding out, Trabert and colleagues used the SEER-Medicare Linked Database to gather information of 16,323 women aged 65 and over who had been diagnosed with endometrial cancer between 1993 and 2007, alongside 100,751 women who were free of the disease.

A diagnosis of metabolic syndrome among the women was given using criteria set by either the US National Cholesterol Education Program Adult Treatment Panel III (ATP III) or the International Diabetes Foundation. The results of the analysis revealed that women who had been diagnosed with metabolic syndrome using the ATP III criteria were 39% more likely to be diagnosed with endometrial cancer, while women diagnosed with metabolic syndrome using the International Diabetes Foundation were 109% more likely to be diagnosed with the cancer.

After accounting for overweight or obesity among the women, the researchers found that those diagnosed with metabolic syndrome under ATP III criteria were still 21% more likely to be diagnosed with endometrial cancer, while an International Diabetes Foundation diagnosis of metabolic syndrome put the women at 17% higher risk of the cancer.

In addition, the researchers identified four factors involved in metabolic syndrome – excessive weight, high blood pressure, high triglycerides and impaired fasting glucose – that raised the risk of endometrial cancer individually.

“We found that a diagnosis of metabolic syndrome was associated with higher risk of endometrial cancer, and that metabolic syndrome appeared to increase risk regardless of whether the woman was considered obese.

Although our study was not designed to evaluate the potential impact of preventing metabolic syndrome on endometrial cancer incidence, weight loss and exercise are the most effective steps a woman can take to prevent developing metabolic syndrome.”

Commenting on the team’s findings, Trabert says: