Appetite Regulation and the Brain

Before we get back to sleeping, there's a bit of brain signaling that it is important to get a handle on.  Most of this information is derived from rodent studies, but I have no reason to believe their brain signaling about appetite and whatnot would be much different from our own.  I want to go over this bit about satiety and hunger pathways in the brain because they overlap with the sleep pathways that we will cover next. 

The center of appetite is in the hypothalamus of the brain.  The most important part of the hypothalamus with respect to appetite is the arcuate nucleus.  (When we talk about neurons, a nucleus is generally a collection of neuron cell bodies with long branches called axons that spread out to different brain regions, spreading signals along the way).

Now it is time to introduce some players.  Bear with me, as there are a few too many.  Within the arcuate nucleus,  one set of neurons makes CART and POMC.  POMC is cut up into a neurotransmitter called alpha melanocyte-stimulating hormone.  This critter acts on various areas of the hypothalamus to reduce appetite.  Another set of neurons in the arcuate nucleus makes appetite-increasing neurotransmitters and sends axons to the same areas of the brain as the POMC (appetite reducing) neurons.  The appetite increasing chemicals are AgRP and neuropeptide Y.

Quick recap - arcuate nucleus of the hypothalamus is the nerve center for appetite regulation.  It is responsible for sending out appetite reducing neurotransmitters (alpha melanocyte-stimulating hormone) and appetite increasing neurotransmitters (AgRP and neuropeptide Y).

Now, these things are always beautifully regulated via negative feedback loops.  The POMC neurons and the AgRP and neuropeptide Y neurons project signal to an area of the brain called the paraventricular nucleus.  (Don't let all the long names blow your mind.  They are just names.  Maybe we should rename them Robb Wolf, Mark Sisson, Melissa McEwen, or Richard Nikoley to make them more friendly.)


The paraventricular nucleus synthesizes and secretes two appetite-reducing neuropeptides (corticotropin-releasing hormone - yes, that corticotropin releasing hormone - and oxytocin) in response to the stimulus by the appetite increasing neurotransmitters.  The arcuate nucleus also sends projections to the lateral hypothalamus to stimulate the appetite increasing hormones melanin-concentrating hormone (MCH) and the orexins.  It is these last two appetite-increasing hormones that have a lot of overlap with sleep regulation, and even mood.  I'll get to them in a few days.

Phew.  Now let's get a bit more big picture.  The arcuate nucleus is the epicenter of appetite control and receives a lot of signals from outside players.  The presence of glucose, and also long chain fatty acids such as oleic acid (the primary component of olive oil, but also a major component of most animal fats) in the arcuate nucleus will inhibit feeding behavior and peripheral glucose production.

And remember those CART/POMC (appetite reducing) and AgRP/neuropeptide Y (appetite increasing) cell bodies in the arcuate nucleus?  Turns out they are the major site of action in the hypothalamus of the hormones leptin and insulin.  Both those hormones will tend to reduce appetite by suppressing the AgRP/neuropeptide Y neurons. 

Have I lost everyone yet?  There is a slew of wondrous basic science research into appetite regulation in the hypothalamus.  One of the cooler things to do is to infect the hypothalamus with various genetically modified adenoviruses* (I know, it does sound like the first act of a zombie movie).  If the adenovirus carries a gene that activates the signal of "low energy availability" (for biochem geeks, this is AMP kinase), the mice increase food intake and gain weight (maybe they will be hungry for BRAINS).  If the virus signal suppresses the low energy signal, the mice will stop eating and get a bit too slender.  Our "food is aplenty" hormones insulin and leptin will decrease the "low energy available - so EAT" signal, whereas known bingey hormones cannabis and ghrelin will increase the appetite signal and lead you to eat. 

So for many, many years, researchers have known that glucose and insulin seem to decrease appetite.  (BUT BUT BUT what about diabetes and gaining weight and too much insulin and glucose!!!!  Yes, in that case the negative feedback is broken, likely through inflammation and damage in the hypothalamus - so you need more and more glucose and more and more insulin to give the signal to cut off the appetite, and protuberant bellies and sales of "Sweatin' to the Oldies" increase accordingly).  I think this basic science, in combination with a false sense of security about high carb diets causing increased insulin sensitivity in the periphery (as opposed to low carb diets, which will physiologically increase insulin resistance in the skeletal muscle), is what led to the misguided advice for diabetics to consume carbohydrate-rich diets all these years.  It was only recently (well, 2002) that oleic acid, for example, was found to significantly reduce appetite also.  (And that basic science finding pretty much coincides with the massive enthusiasm for olive oil and the Mediterranean Diet).

Um, I hope I still have a few readers by the end of this post!  Go out there and eat healthy and get some sleep.  Your hypothalamus will thank you, as will your less protuberant belly.

As always, a big thanks to Jamie Scott, who has sent me the major reference article for today's post.

*there was a recent study showing that kids who had previous infection with adenovirus-36 were much more likely to obese than kids with no previous infection.  No, I doubt it is the mutant strain that escaped the lab.  Antibodies to adenovirus-36 are also found in 30% of obese adults.**

**get some sunshine to boost your vitamin D to ramp up antiviral immunity.