I have missed you! I have missed the constant stream of awesome science! I have missed SFN and its craziness! A lot of missing is happening folks. Now that we are back, we are trying to digest the insurmountable amount of information that was dumped on us and trying to integrate some awesome ideas into our research. As I mentioned in our Daily Diaries’ that we attended quite a number of lectures, and from these lectures we have been oh so inspired! So for a couple of upcoming posts we will be using these lectures as a foundation of the blog posts.
Leptin. The hormone that was thought to be the answer to obesity when it was discovered via ob/ob mice in 1994 by Jeffrey Friedman’s lab. Characterized by studying a mouse model that had a recessive genetic obesity, called the ob/ob mice which were sterile mice which over 50% body fat (Google Image ob/ob mice, you know how we feel about being trouble for using someone else’s picture)Leptin has put researchers, clinicians and pharmaceutical companies through the ringer since its discovery. Initially touted as being the be all end all of controlling obesity, due to it decreasing body weight & increasing energy expenditure, it was soon realized that it was not as simple as that (more on leptin and obesity in another post).
Leptin, predominately synthesized by your adipose tissue (fat cells), is central to the regulation of energy intake, energy utilization, & metabolism (pretty much everything relates to it). When humans are in a neutral energy balance (basically that the number of calories consumed are just enough to satisfy their metabolic needs) the levels of leptin expression and secretion is representative the amount of body fat mass. Leptin levels are elevated in humans days after over eating, and are decreased in hours after fasting is initiated.
It’s important to note that leptin receptors are widely expressed not only in the periphery of the body but also the brain, making it difficult to study specific regions.
Dr. Martin Myers, from the University of Michigan, talk largely covered a paper, which he and his group have recently published in Cell Metabolism. I am gonna give you lovelies, a brief (very brief) snippet of the paper. Through a series of elegant experiments they haves specifically looked at leptin receptors expressed in the lateral hypothalamus which contain neurotensin (LepRbNts), a neuropeptide that interacts with the dopaminergic system. These neurons are activated by leptin and are part of network that is connected to a population of orexin (also known as hypocretin, are implicated in wakefulness, food intake and energy expenditure) neurons and the ventral tegmental area (VTA, we will look into the wonderful world of the VTA in another post). The researchers found that these neurons are regulating orexin expression and the activity of these neurons. This suggests that LepRbNts neurons may be involved in the physiologic leptin action of the orexin neurons.
They generated a strain of mice that were without leptin receptors on the neurons that expressed neurotensin (Nts-LepRbKO) this resulted in the mice exhibiting early-onset obese phenotype, increased feeding and decreased locomotor activity. This strain revealed to have altered regulation of the orexin neurons and the mesolimbic dopamine system. Their overall take home message, is that there are important roles in which leptin action ‘s on LepRbNts neurons in relation to controlling energy balance and neurophysiology.
If you even have a remote interest in leptin, energy metabolism, interesting methods, or just really really pretty pictures, I highly recommend checking the paper out. It is published in Cell Metabolism, which may make it difficult to get, however hustle your librarians, supervisors, fellow bloggers, nerdy friends and if all else fails, shoot as an email and we will hook you up;)
coughsuperstarcough → Dr.Myers portfolio
Leinninger GM, Opland DM, Jo YH, Faouzi M, Christensen L, Cappellucci LA, Rhodes CJ, Gnegy ME, Becker JB, Pothos EN, Seasholtz AF, Thompson RC, & Myers MG Jr (2011). Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell metabolism, 14 (3), 313-23 PMID: 21907138