The dietetic internship program that I am completing is combined with a Masters in Human Nutrition and Food. Therefore, in addition to rotating with various dietitians, I am taking graduate courses as well. Last year was all courses, and I had one more course to take this year: a seminar course.
Essentially, that means that a group of graduate students and professors in a department meet once or twice a week and each student will choose a specific topic within a broader topic. The broad topic for this semester was “Physiologic Regulation of Food Intake”, i.e. the various hormones and peripheral metabolic systems within the body that affect appetite, digestive systems, etc.
As I started to look for a topic, I came across a molecule discovered in 2006 that was named “Nesfatin-1”. The name itself, and the fact that it was so recently discovered intrigued me.
Using library databases, I compiled a sizable stack of journal articles on this one little satiety molecule.
I read them. And re-read them. And found a few more articles. And tossed a handful. Trying to wrap my mind around the hypothesized way that Nesfatin-1 sends signals within the hypothalamus- a key feeding regulator in the brain.
I’m pretty sure I spent upwards of 80 hours studying charts and graphs and immunostaining pictures and critically examining the work of researchers.
Sticky notes were all over my wall.
And the desktop of my computer was covered with screen shots of various charts and graphs. They covered up the face of my sweet newborn niece which is currently set as my wallpaper.
“Nesfatin” is a name coined by the Japanese researchers who first discovered the satiation properties of this Nucleobindin2-encoded satiety and fat–influencing protein (1). It is a 396 amino acid molecule attached to a 24 amino acid signal peptide that is located in several areas within the brain and has also been identified in other areas of the body.
In my presentation, I focused mostly on research looking at the effects in the paraventricular nucleus of the hypothalamus and the nucleus tractus solitarius of the brain stem. As with any molecule in the body, it is highly complex and difficult to identify a clear mechanism of action.
This is the proposed mechanism that I presented:
As a note, “anorexia” in this case simply means a reduced appetite, not the clinically diagnosed eating disorder “anorexia nervosa”.
As a result of my research, I propose that in the future, nesfatin-1 could potentially be a biomarker for monitoring/diagnoses of diseases, as well as used therapeutically in metabolic diseases. However, a lot more research must be done before anything like this could be used.
Future research could focus on characterizing nesfatin-1 levels across various populations and identify the local of expression in both the brain and periphery of the body.
Conclusions of my study include that Nesfatin-1 appears to be a potent regulator of food intake in rodents (1,2), that it appears to work via a leptin independent mechanism, implying potential application in leptin resistance (1,2).
1. Oh-I S, Shimizu H, Satoh, T, et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature. 2006;443:709-712.
2. Maejima Y, Sedbazar U, Suyama S, et al. Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway. Cell Metabolism. 2009;10(5):355.