Obesity in mice can be ameliorated by transplantation of hypothalamic neurons

The db/db mouse is widely employed as model of morbid obesity and its main feature is that it lacks of the receptor of a hormone called leptin. This hormone plays a major role in the hypothalamus, were things like sleep, thirst, body temperature, and hunger are regulated.

In a recent study published in Science, Czupryn et al., showed that increasing leptin-receptor containing neurons in the hypothalamus could work to help db/db mice to reduce weight. They took newborn db/db mice and controls, and gave them an implant of neurons containing the leptin receptor. After the mice grew up, the authors found that the neurons were able to express the leptin receptor in the hypothalamus. The result was a lower body weight in mice treated with the leptin expressing neurons compared to non-treated db/db mice, but not as low as control mice.

Still, though it’s not the whole answer, it’s an interesting start to understanding not only the role of the hypothalamus in obesity and type 2 diabetes, but also how we might be able to change receptors in the brain to restore leptin sensitivity, and decrease sever obesity and the type 2 diabetes that often goes with it.

Source: Scientific American and
Czupryn, A., Zhou, Y., Chen, X., McNay, D., Anderson, M., Flier, J., & Macklis, J. (2011). Transplanted Hypothalamic Neurons Restore Leptin Signaling and Ameliorate Obesity in db/db Mice Science, 334 (6059), 1133-1137

New drug to prevent pregnant obese women to give birth to obese babies

A UK trial will soon be under way whereby a commonly used diabetes pill will be administered to obese pregnant women in an attempt to prevent overweight mothers from delivering obese babies.

Obese women who become pregnant are generally at risk of complications such as pre-eclampsia (potentially fatal), fetal death, possible birth defects and a greater number of caesarean deliveries. Children born to obese mothers are twice as likely to be obese and to develop type 2 diabetes later in life. Obesity during pregnancy is also associated with greater use of health care services and a longer hospital stay.

Given the disturbing trend of increasing obesity among women in many developed countries, the answer is, apparently, to counter this by medicating babies while still in the womb. The trial will involve 100 obese but non-diabetic volunteers at hospitals in Liverpool and Coventry, England and Edinburgh, Scotland. Half will take the drug Metformin after the first trimester of their pregnancies and the other half will take a placebo.

Many weight loss groups and others feel that this news is most disturbing and gives the message that there is a solution to conditions such as obesity, which involve simply taking a pill as a "cure". The emphasis, they feel, should be on encouraging mothers-to-be to lose excess weight before even considering bringing a child into the world.

Studies have consistently shown that lifestyle modification that includes a healthy diet, regular exercise and weight management can prevent the many and various conditions associated with obesity, such as diabetes, gestational diabetes mellitus, and so on.

The ethics of medicating babies while in the womb, or the possible long-term effects of administering drugs of this nature, are also reasons for concern.

Source: http://www.telegraph.co.uk/health/h...

Is there a link between air pollution and obesity?

Medical research has long supported the fact that exposure to ultrafine particulate matter increases the risk of various respiratory, cardiovascular, and pulmonary illnesses. Incidences of asthma, heart attacks, and chronic bronchitis are all higher in areas where the concentration of ultrafine particulate matter is higher. The correlation between particulate matter and these health issues is particularly pronounced in children, as well as low-income communities, which are often located closer to the sources of particulate matter (highways, factories, power plants) than their higher income neighbors.

Over the past decade, new studies have emerged that link air pollution to two of this country’s most pressing (and expensive) health epidemics: obesity and type II diabetes. Both are not only on the rise in terms of diagnoses, but also in terms of the costs associated with treatment. Even after controlling for factors such as genetics, income levels, weight, diet and exercise, Harvard researchers found a “consistent and significant” relationship between Type II diabetes prevalence and exposure to ultrafine particulate matter in a recent study published in Diabetes Care.

Results of an animal study published by Ohio State University researcher Qinghua Sun in late 2010 revealed that early exposure to ultrafine particulates led to the accumulation of abdominal fat and insulin resistance in mice even if they ate a normal diet. Exposure levels for animals in the study were similar to those found in U.S. cities.  The study compared mice fed a high-fat diet with those fed a normal, healthy diet, and exposed some members of both groups daily to ultrafine particulate matter, controlling for all other factors. In the end, all of the mice exposed to air pollution, including those fed a normal diet, had increased abdominal and subcutaneous (under the skin) fat.

These findings suggest that fine particulate pollution exposure alone, in the presence of a normal diet, may lead to an increase in fat cell size and number, and also have a proinflammatory effect.

Source: http://www.forbes.com/sites/amywestervelt/2011/10/10/two-new-reasons-to-worry-about-air-pollution-obesity-and-diabetes/

A Pablo Picasso painting donated to an Australian university was sold in June for £13.5 million at auction. The proceeds will benefit obesity, diabetes and cardiovascular research at the University of Sydney.

The work depicts his lover Marie-Thérèse Walter, whom he met in 1927 when she was 17 and he 45. The painting was snatched up by art collector Walter P. Chrysler Jr., son of the automobile tycoon, before being sold to the anonymous donor. Christie's puts its value at £9 million to £12 million (US$14 million to $18 million).

It is not clear why the donor picked the University of Sydney as the beneficiary for the Picasso, or why diabetes, obesity and heart research was chosen to benefit. In a statement, the university’s vice chancellor Michael Spence said the proceeds “will create multiple endowed chairs across several disciplines within a new multidisciplinary University centre dedicated to research into obesity, diabetes and cardiovascular disease”.

Source: http://blogs.nature.com/news/2011/06/a_picasso_fetches_135_million.html

Naringenin, a compound from grapefruit, helping to reduce insulin resistance

A complex of naringenin and cyclodextrin may help to substantially reduce the absorption of fat and sugar in the body, according to study published in PLoS One.

The research team, from Harvard and the Hebrew University of Jerusalem, found their complex increases the absorption of naringenin by 11 times. They reported that a single dose given to rats before a meal reduced the generation of very low density lipoprotein (VLDL) by 42 per cent, whilst insulin sensitivity was boosted by 64 per cent. The authors claim that their research is the first demonstration that a dietary supplement can change the way our body can react beneficially to a meal.

In recent years, polyphenols, and flavonoids in particular, have emerged as a class of natural products shown to have anti-oxidant, anti-atherogenic, and normolipidemic effects. One of the most abundant flavonoids is the citrus flavonoid-glycoside naringin, which is broken down into naringenin.

Previous research has previously shown that naringenin, responsible for the bitter taste in grapefruits, could potentially be used in the treatment of diabetes, arteriosclerosis and hyper-metabolism. However,  the absorption of naringenin in its natural form is usually very low, reducing its bioavailability. The solubility and transport through the intestinal epithelium of naringenin can be enhanced by forming a complex with a chyclodextrin.

When the complex was administered to rats just prior to a meal it caused a decrease in VLDL levels by 42% and increased the rate of glucose clearance by 64% compared to naringenin alone.

Source: PLoS ONE
Published online ahead of print, doi:10.1371/journal.pone.0018033
“Enhancement of Naringenin Bioavailability by Complexation with Hydroxypropoyl-β-Cyclodextrin”
Authors: M. Shulman, M. Cohen, A. Soto-Gutierrez, H. Yagi, H. Wang, et al

BMI may not be the right tool to measure health risks

The BMI is easy to measure, cheap to compile and track, and simple to convey to patients, but it was never meant to be a predictor of an individual's health risks. It was intended as a useful metric to track changes in the health and nutrition of large populations. For patients who are very muscular, and for African Americans, BMI is often a poor gauge of body composition. For Asians and people who are sedentary but slim, a reliance on BMI can lead a physician to overlook signs of elevated disease risk. A child's BMI, which is calculated differently than that of an adult, is also an imperfect predictor of illness or early death.

The BMI continues to dominate research on obesity and guide physicians' advice to patients. But some researchers have launched a rear-guard effort to knock the measure from its place atop the public-health pedestal. To replace — or at least supplement — the BMI, they are searching for measures that might offer individual patients a better gauge of their health risks, as well as a wider range of options to better their odds of staying healthy.

They'll also need tools to do so that are as cheap and simple as the BMI. Most techniques that measure body composition, including the Bod-Pod, the dual-energy X-ray absorption test (DEXA), and hydrostatic underwater weigh-in, are costly and time-consuming. Bioelectrical Impedance Analysis, an inexpensive and reliable gauge of body composition increasingly used in weight-management programs, may be practical in some general medical practices. But researchers are increasingly looking for ways to capture such information with tools as simple and inexpensive as tape measures.

One of the easiest alternatives to the BMI is waist measurement. With growing evidence that fat girdling the waist and visceral organs disturbs metabolism, the circumference of a patient's midsection has been shown to be a better predictor of Type 2 diabetes risk than the BMI.

Finally, an increasing number of researchers cite a major gap in the BMI: its inability to reflect the health effects of an individual's exercise habits. At least seven high-profile studies in the last decade have established that even for people with high BMIs, cardiovascular risk and the likelihood of early death are driven down significantly by maintaining a high level of fitness or at least regular physical activity. The risk of Type 2 diabetes also falls, although in that case, studies suggest that whittling waist circumference is a better strategy still.

Source: L.A. Times

Obesity Problems Fuel Rapid Surge Of Type 2 Diabetes Among Children

Today, about 3,700 Americans under the age of 20 receive a diagnosis annually of what used to be called "adult-onset" diabetes, according to the Centers for Disease Control and Prevention. That relatively small number makes it a rare disease in children, but it represents a trend with larger ramifications.

"In a little more than 10 years, the numbers went from nothing to something," says Larry Deeb, a pediatric endocrinologist and past president of the medicine and science division of the American Diabetes Association. "And that's something to worry about."

Diabetes can cause a litany of medical woes, including heart disease, kidney failure, limb amputations and blindness. It costs the U.S. health-care system $174 billion a year, according to the National Institutes of Health.

Those statistics are grim enough when patients are in their 60s. When the diagnosis is made decades earlier, new fears are raised: Will these children suffer heart attacks in their 20s, need kidney dialysis in their 30s or go blind before they see their own children graduate from high school?

Because about 80 percent of Type 2 diabetes patients are overweight or obese, it's not surprising that patients such as Annie ask if they've done this to themselves. But there are other risk factors that no one can control: family history, ethnicity (blacks, Hispanics and American Indians have higher rates of diabetes), genetics or a mother who had diabetes during her pregnancy.

Instead of wallowing in regret, doctors suggest that young patients and their parents seize the opportunity for a crash course on how to improve their health.

"I used to wear a button that said 'Stamp Out Guilt,' " says Fran Cogen, director of the Child/Adolescent Diabetes Program at Children's National Medical Center in Washington, D.C. "I try to tell people that no one caused their diabetes. I emphasize that they can make changes now."

Alarm bells are going off among those who study diabetes in children because of what they know about the adult version of the illness. More than 25 million Americans have diabetes (more than 90 percent have Type 2), according to the National Institute of Diabetes and Digestive and Kidney Diseases -- but another 79 million have a condition called pre-diabetes, in which blood sugar levels are higher than normal but not as high as in diabetes.

Pre-diabetes isn't a disease requiring medical treatment -- it's a wake-up call. A large national study showed that adults with pre-diabetes who lost 7 percent of their body weight reduced their risk of diabetes by 58 percent.

Officials are concerned that the number of children already identified as having Type 2 diabetes is just the tip of the iceberg. In a national study of 2,000 eighth-grade students from communities at high risk for diabetes, more than half of the kids were overweight or obese. Only 1 percent had diabetes - but almost a third of them had pre-diabetes, according to Lori Laffel, chief of the Pediatric, Adolescent and Young Adult Section of the Joslin Diabetes Center in Boston and a principal investigator on the study.

It's crucial, she says, to find those children before their condition progresses to diabetes so that it can be reversed by lifestyle changes, without medication.

Making Progress

If there is any good news in childhood diabetes, it is that pediatricians are starting to look for it.

"It's in the news, and all over the medical literature," says Susan Conrad, a pediatric endocrinologist at Inova Fairfax Hospital. "Pediatricians are on top of it."


For example, sometimes children whose bodies are beginning to have problems regulating insulin develop a telltale dark, velvety rash around their necks. A decade ago, such a child might have been referred to a dermatologist.

In addition, CDC guidelines suggest that a child with a family history of diabetes, or one whose weight is above the 85th percentile for age and sex should be screened, with blood and urine tests, for diabetes.

Family experiences made John Perrone of Winchester, Va., aware of diabetes and its consequences. John's mother, who developed gestational diabetes during all three of her pregnancies, now has Type 2 diabetes. His mother's aunt had diabetes, and by the time she died in her 70s, she was on dialysis, in a wheelchair, legally blind and had suffered two strokes.

John got a diagnosis of Type 2 diabetes four years ago, and he has worked hard ever since to keep the disease under control. He says he's gone from an overweight 11-year-old to a husky but fit 15-year-old. He has progressed from needing insulin injections to keeping his glucose under control with oral medication, combined with healthful eating and a lot of exercise.

He has learned enough to want to teach other kids with the disease. As an Eagle Scout project, he has developed a PowerPoint presentation aimed at youngsters. He has translated medical terms, such as glucose and glucometer, into words they understand, such as sugar and meter. He has also wanted to simplify for kids the basics of weight loss, which is so crucial for diabetes control.

"It's all about in and out, what you eat, how much you exercise," he says. "Maybe if kids understand it better, they can do it."



Source: Kaiser Health News