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Musing about various life issues, I am often surprised at how little in my regular day I recognize concepts that are fairly obvious – things that I just haven’t taken the time to consider. One topic that falls into this category is that food is a ridiculously large part of our culture. Holidays revolve around meals, people bond when eating together, and people eat for fun and comfort, not just for sustenance. Food has become a pastime and entertainment, and it often signifies the importance of an occasion and sets a mood – it can be viewed as an art. In fact, I can’t really think of anything that’s as routinely and prominently celebrated as food, especially in American society. It may be due to this that we as a society have so many health problems relating to eating and nutrition; obesity and diabetes are two major issues that have been increasing in prevalence over the years and have gained attention as the foremost health problems in the US, as well as possible contributors to other diseases and disorders. Clearly, these are issues that need to be dealt with, but the question is, how?

I mean, if I need to send my grandma after you every time you go for a second dessert, I will.

Likely the most effective targets for treatment of obesity, especially, are the insulin and leptin signaling pathways, leading to a decrease in food intake to aid in losing weight. Insulin and leptin are hormones that play influential roles in energy intake and homeostasis; leptin in particular acts in the brain to signal the feeling of being full. The general pathway of insulin and leptin signaling in a well-functioning system starts with the digestion of food inducing the secretion of insulin from the pancreas and release of leptin from fat tissue. These hormones then travel through the bloodstream and activate receptors in a part of the brain that controls energy homeostasis via signaling related to food intake and metabolism. Neurons expressing the polypeptide proopiomelanocortin (POMC), when activated, will secrete the neuropeptide α-MSH which works to signal for decreased food intake and increased energy expenditure. Conversely, neurons expressing neuropeptide Y (NPY) and agouti related protein (AgRP) are activated by a decrease in insulin and leptin, resulting in signaling for increased food intake and decreased energy spending. Although similar in resulting cellular responses, NPY and AgRP work in different ways; NPY directly activates pathways which lead to increased food intake, whereas AgRP blocks the α-MSH receptor, inhibiting the pathway leading to decreased food intake.

The insulin and leptin signaling pathways themselves are also quite similar in cellular response, as they share a common downstream effector molecule – although the two receptors may have different primary effectors that begin two signaling cascades, these cascades converge on a single molecule and therefore share the ends of their pathways. The receptors’ primary effectors may have multiple signaling routes which do not converge with that of the other’s, but it has been shown that there exists at least one molecule on which signaling pathways from these two receptors converge. This indicates that there is a high level of cross-talk between the pathways of insulin and leptin, so a change in one highly affects the other.

I really hope the pictoral representations of these are accurate — it’s like our neurons are tiny bowls of Lucky Charms.

Here’s the issue with the idea of manipulating the insulin and leptin systems to treat obesity and other diseases relating to overnutrition: long term treatment will only end in patients being dependent on it to maintain their weight, since a treatment directly affecting energy homeostasis will swing the energy balance the opposite way if discontinued. Diet pills notoriously give great results for weight loss in the short term, but after patients have stopped taking them, the weight comes right back and then some. I don’t believe that any outside treatment acting on the body for weight loss would be truly effective without lifestyle change – that is the necessary and lasting component to fitness and physical health. I support these pharmaceutical treatments for those who need help to achieve an initial weight loss in order to make exercise more feasible, but anything less than a necessity like that would only make things harder in the long term. Sometimes, if not often, the simple answer is the best answer – maybe appropriate nutrition and exercise are the cure-all for the health problems in today’s society.

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