Quitting Smoking Without Gaining Weight

Quitting Smoking Without Gaining Weight

  3:41:00 PM    Science Lover

---

Smokers tend to die young, but they tend to die thinner than non-smokers. A team of scientists led by Yale School of Medicine has discovered exactly how nicotine suppresses appetite -- findings that suggest that it might be possible to develop a drug that would help smokers, and non-smokers, stay thin.

Scientists have discovered exactly how nicotine suppresses appetite -- findings that suggest that it might be possible to develop a drug that would help smokers, and non-smokers, stay thin.

Nicotine activates a small set of neurons in a section of the hypothalamus that signals the body has had enough to eat, the researchers report in the June 10 issue of the journal Science. Nicotine accomplishes this trick by activating a different set of receptors on the surface of neurons than those that trigger a craving for tobacco.

"Unfortunately, smoking does keep weight off," said Marina Picciotto, the Charles B.G. Murphy Professor of Psychiatry, professor of neurobiology and pharmacology and senior author of the paper. "Many people say they won't quit smoking because they'll gain weight. Ultimately, we would like to help people maintain their body weight when they kick the habit and perhaps help non-smokers who are struggling with obesity."

Picciotto is an expert on the function of nicotine receptors located on the surface of neurons. Nicotinic acetylcholine receptors have many functions, and in the brain are the primary targets of nicotine. Yann Mineur, an associate research scientist in her lab, was investigating a potential drug for depression that acts upon these receptors when he noticed that mice given the drug ate less than those not on the medication. With the help of researchers at Carleton University in Ottawa and the University of Hawaii, they decided to investigate why.

In a variety of experiments, the researchers found that the experimental drug activated a specific type of nicotine receptor, which in turn activated the subset of neurons in the hypothalamus, called pro-opiomelanocortin or POMC cells. The team also found that when subjected to nicotine, mice lacking the POMC pathway did not lose weight, unlike mice with the pathway intact. Intriguingly, they also showed that these receptors were of a different type than those known to trigger tobacco craving in smokers.

"This suggests it is possible to get the effect of appetite suppression without also triggering the brain's reward centers," Picciotto said. Baylor College of Medicine contributed to the study. Other Yale authors are Yan Rao, Ralph J. DiLeone, Sabrina Diano, Tamas L. Horvath and Xiao-Bing Gao.

The study was funded by the National Institutes of Health.

Read More

Gene Therapy Reverses Type 1 Diabetes in Mice

Gene Therapy Reverses Type 1 Diabetes in Mice

  9:35:00 PM    Science Lover

---

Researchers have developed an experimental cure for Type 1 diabetes, a disease that affects about one in every 400 to 600 children and adolescents.

In a new study using gene therapy in mice, researchers 
say they have developed an experimental cure for 
Type 1 diabetes. (Credit: iStockphoto)

Results of the research in a mouse model of Type 1 diabetes are being presented at The Endocrine Society's 92nd Annual Meeting in San Diego.

Using gene therapy, the team from Baylor College of Medicine in Houston tried to counter the two defects that cause Type 1 diabetes: autoimmune attack and destruction of the insulin-producing beta cells. They used nonobese diabetic mice, which spontaneously develop diabetes due to autoimmunity, just as humans do with Type 1 diabetes.

"A single treatment cured about 50 percent of the diabetic mice, restoring their blood sugar to normal so that they no longer need insulin injections," said study co-author Lawrence Chan, MD, DSc, chief of Baylor's diabetes, endocrinology and metabolism division.

Type 1 diabetes occurs when the body's immune system attacks and destroys the beta cells in the pancreas, the insulin "factory" of the body. The resulting near-complete deficiency of insulin -- the hormone that controls blood sugar -- leads to a buildup of high blood sugar and thus diabetes.

In past studies of their original gene therapy, Chan's group was able to stimulate new formation of beta cells in the liver and restore insulin production and normal blood sugar levels in more than 100 mice with chemically induced diabetes. However, in nonobese diabetic mice the treatment failed to reverse Type 1 diabetes because the mouse's immune system killed the newly formed beta cells, he said.

In this research, which was funded by the National Institute of Diabetes, Kidney and Digestive Diseases, Chan said they "added to the original gene therapy approach a protective gene that shields the newly formed beta cells from autoimmune attack." The added gene was for interleukin-10, an important regulator of the immune system. Past studies showed that interleukin-10 can prevent diabetes development in mice but cannot reverse the disease once it has developed because of the lack of beta cells.

However, when the researchers combined the gene therapy with interleukin-10 into a single intravenous injection, the treatment showed a complete reversal of diabetes in half of the mice during more than 20 months' follow-up. Although the therapy did not reverse autoimmunity throughout the body, it protected the new beta cells from the local destructive effect of autoimmunity, Chan explained.

"We developed a protective 'moat' around the new beta cells," he said. "We are now developing other strategies to try to fortify the newly formed beta cells and give them better weapons in addition to the moat, in order to increase the treatment's cure rate."

Why the gene therapy did not work in all the mice is unclear. However, Chan said the treated mice that did not have improvements in their blood sugar did gain weight and lived a little longer than untreated mice.

Read More