Nesfatin-1: obesity, diabetes fighter?
In North America, metabolic diseases such as diabetes and obesity are becoming epidemic among people as well as their pets.
As many as 50 per cent of cats and dogs in domestic households are overweight or obese and science still doesn’t fully understand why some individuals are more prone to metabolic disease than others.
Dr. Suraj Unniappan, an associate professor in the Western College of Veterinary Medicine’s (WCVM) Department of Veterinary Biomedical Sciences, is helping to shed some light on the subject. The researcher is now focusing to better understand the function of a relatively less studied novel protein, nesfatin-1, that was discovered in Japan in 2006.
Nesfatin-1 supresses appetite to make people and animals feel full after a meal. It also stimulates insulin release so that glucose moves from the blood into the cells, thus helping to maintain energy balance. When nesfatin-1 was administered to rats, they not only ate less but used more fat as an energy source and became more active.
Nesfatin-1 is produced throughout the body but has been found to be abundant in the hypothalamus (a region of the brain that regulates feeding and body weight) as well as the fundic region of the stomach and the insulin-producing pancreatic islet beta cells. It’s also found circulating in the blood.
So far, researchers have mainly studied nesfatin-1 in humans, rodents and fish. These studies have shown it’s an important molecule that’s naturally occurring and multi-functional in these species. But other than a couple of recent studies involving pigs and dogs, nesfatin-1 in domestic animals still remains poorly understood.
For my summer research project, I attempted to gain a comprehensive understanding of nesfatin-1 in domestic animals by investigating its expression in the stomach, pancreas and blood of animals including cats, dogs, pigs, horses, cows, sheep, bison, chickens and rainbow trout. The tissue samples were provided by a large number of researchers at the WCVM and the University of Saskatchewan.
Proteins are often studied by using antibodies that are tagged in some way so you can visualize them. For this study, I looked at nesfatin-1 in tissue samples by incubating it with a fluorescently-labelled antibody so it could be viewed under a fluorescence microscope. I also used antibodies to detect it circulating in the blood, but this test uses a colour change reaction to visualize the results.
Using scientific databases, I also collected the sequences for nesfatin-1 from over 100 species of animals and compared them using computer software programs. As it turns out, nesfatin-1 is highly conserved among species. In other words, the sequences are nearly identical in vertebrates and highly similar in some invertebrates. This evolutionarily conserved structure of the protein suggests similar functions for the nesfatin-1 across species.
We expected to find the nesfatin-1 protein in all of our species of interest, especially since it is so highly conserved. What we actually found was that it appeared in the blood of all of our study’s target species as well as in their stomach and pancreas.
There was one exception: we didn’t find nesfatin-1 in the pancreatic islets of cats as we had expected. This is an interesting finding — especially since cats are more prone to metabolic disease. More work needs to be done to understand why they are different than other species.
My research findings are important as it is the first set of information on nesfatin-1 in a large number of domestic animals and provides direction for future studies.
Scientists including Unniappan are exploring the anti-obesity and anti-diabetic potential of nesfatin-1. Since it’s a natural protein that the body makes itself, it would have fewer side effects than compounds that are not. But much more work needs to be done to understand how nesfatin-1 produces its effect in the body and what other functions — some potentially adverse — it may have.
Research in Unniappan’s lab is funded by grants from the Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council (NSERC) of Canada, Canada Foundation for Innovation (CFI) and the Saskatchewan Health Research Foundation (SHRF). My research was funded by the U of S and the WCVM.
Katie Morton of Quesnel, B.C., is a second-year veterinary student who participated in the WCVM’s Undergraduate Summer Research and Leadership program in 2013.