Obesity and Cancer

Are You Overeating

If you are overeating you may be setting yourself up to a vicious cycle that will promote obesity. The results of a new study suggests one way this cycle works is that when the gut senses too many calories, it shuts off a hormone that tells the brain that we are full.

Researchers at Thomas Jefferson University in Philadelphia, Pennsylvania published their findings in the journal Nutrition & Diabetes that they came to this conclusion after observing mice on high-calorie diets.

Using non-obese mice in a previous research on colon cancer, the team had come across a hormone called uroguanylin that is produced in the small intestine and travels to the brain where it signals fullness.

Senior author and professor Scott A. Waldman, chair of pharmacology and experimental therapeutics, building on earlier work along with colleagues, decided to explore how uroguanylin might be involved in promoting obesity.

Mice were put on high-calorie, obesity-inducing diets for 14 weeks, and then monitored what happened to uroguanylin in their guts and brains. They then found that the small intestines of the overfed mice stopped producing uroguanylin and it didn’t matter if the mice were lean and overfed or obese and overfed. The uroguanylin production stopped in both groups of animals when they got too many calories.

When overfed mice were put on a low-calorie diet, their small intestines began producing the hormone once again. These effects are the opposite of what we know about other obesity-related hormones such as insulin and leptin. As weight increases, production of these hormones goes up but it’s not the obese state that’s causing the problem but rather the calories.

The team then examined the cells in the small intestine responsible for uroguanylin production, thinking it might have something to do with the endoplasmic reticulum (ER), which is a cell compartment that acts like a mini factory for proteins and hormones. The ER can stop working if it gets stressed. The mice were then given tunicamycin, a chemical that causes ER stress, by the researchers where they found the animals stopped producing uroguanylin.

It was also found that giving overfed and obese mice a chemical known to relieve ER stress caused their gut to resume production of the hormone.

It is suggested by the researchers that along with other approaches, hormone replacement of uroguanylin may become an important component of therapy to reverse obesity. A lot more research will need to be done. There are many steps to becoming obese that are not easily reversed and studies need to find out whether the uroguanylin pathway is important early or late in the process and how big an influence it has compared with other pathways.

In view of these findings, let’s all just put up those extra foods and snacks and eat a little less to help our “fullness signal” work for us!

Dr Fredda Branyon

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