The Hormones of Hunger

January 29, 2013 in Categories: by

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I want to delve into the effects of diet and lifestyle on hunger and satiety signals in a series of upcoming posts.  I am mostly interested in the hormone dysregulation that occurs during metabolic syndrome, but also in how to optimize diet, exercise, sleep and stress management to achieve an ideal weight.

The feeling of hunger is regulated by a complex system of hormones that interact with neurotransmitters and neurotransmitter receptors within the hypothalamus region of the brain.  These hormones essentially activate or deactivate specific neurons in the hypothalamus that control hunger.  These neurons have receptors to Neuropeptide Y (NPY), the essential neurotransmitter in regulating hunger.  The hormones can increase or decrease hunger either through binding the receptors for NPY or increasing or decreasing NPY itself.  Essentially a hormone will increase hunger if its expression activates these NPY neurons whereas you will feel satiated if a hormone’s expression deactivates the NPY neurons.  The interplay between these hormones and your brain is complex and only partially understood.  However, what scientists do know about these hormones can help inform our decisions and compulsions regarding diet and other lifestyle factors. 

New hormones continue to be discovered and their roles in regulating appetite, satiety, metabolism and digestion continue to be studied.  As the full list of hunger hormones grows, understanding the complex interplay between these hormones, the types of food you eat, and the amount of muscle and fat on your body quickly becomes overwhelming.  I have tried to summarize the key players (at least as scientists currently understand them):

Hormones that tell your body you’re satiated:

Cholecystokinin (CCK) is secreted by the cells that line the duodenum (the first segment of the small intestine) when they detect the presence of fat.  This causes the release of digestive enzymes from the pancreas and bile from the gallbladder.  Increased levels of CCK signals to the stomach to slow down the speed of digestion so the small intestine can effectively digest the fats.  CKK is also a neuropeptide similar to NPY and has a direct action on neurons in the brain to signal satiety.  This is the most immediate hunger suppressing signal and is the reason why eating fat with your meals is so important.

Oxyntomodulin is released in response to protein and carbohydrates in the stomach and signals a change in energy status to the brain.  Oxyntomodulin enhances digestion by delaying gastric emptying and decreasing gastric acid secretion.

Peptide YY (PYY) is released by cells that line the jejunum, ileum (the next two segments of the small intestine) and colon in response to feeding and is especially sensitive to protein.  PYY signals to the gallbladder and pancreas to stop producing digestive enzymes.  PYY is important in increasing the efficiency of digestion and nutrient absorption after meal by slowing down gastric emptying, slowing down the speed of digestion, and increasing water and electrolyte absorption in the colon.  PYY interacts directly with NPY receptors in the hypothalamus in an inhibitory fashion, thereby turning off hunger signals.

Glucagon-Like Peptide-1 (GLP-1) is secreted in the ileum in response to carbohydrate, protein and fat.  It rapidly enters the circulation and is one of the fastest and shortest-lived satiety signals.  It inhibits acid secretion and gastric emptying in the stomach.  GLP-1 also increases insulin secretion and decreases glucagon secretion.  GLP-1 decreases hunger signals by reducing the amount of NPY.

Leptin plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism.  Leptin is released both by adipocytes (fat cells) and by the cells that line the stomach, so it signals both that the body is fed and that there is sufficient energy storage.  This appetite inhibition is long-term, in contrast to the rapid inhibition of eating by CCK and the slower suppression of hunger between meals mediated by PYY.  Leptin both rapidly inhibits NPY production and deactivates NPY neurons in the brain to signal that the body has had enough to eat, producing a feeling of satiety. It is one of the most important adipose derived hormones (read more in this post).

Adiponectin is secreted from adipose tissue into the bloodstream where it signals decreased gluconeogenesis (when the body converts fats and proteins into  glucose for energy), increased glucose uptake, lipid catabolism (breaking down of fats), triglyceride clearance (storage of fats), increased insulin sensitivity, and control of energy metabolism.  Adiponectin acts directly on NPY neurons similarly to leptin but with additive effects.

Hormones that tell your body you’re hungry:

Ghrelin is considered the main hunger hormone.  It is secreted by the cells that line the stomach when the stomach is empty and also by the pancreas when it detects low blood sugar.  Also, the liver secretes ghrelin when its glycogen storage runs low (and glucagon is high).  When ghrelin is released into the circulation, it directly activates NPY neurons to stimulate appetite.  Increased levels of ghrelin are directly associated with the sensation of hunger. It is considered the counterpart of the hormone leptin.  Importantly, ghrelin is a potent stimulator of growth hormone (GH) secretion and regulates nutrient storage, thereby linking nutrient partitioning with growth and repair processes. Ghrelin activates several anti-inflammatory pathways in the body and promotes cell regeneration thereby promoting healing, especially within the gastrointestinal tract. Ghrelin regulates glucose homeostasis through a direct action on the pancreatic islet cells (the cells that secrete insulin).  It is also important for memory function and gastrointestinal motility.

Cortisol is well-known as a stress hormone, but it has key roles in regulating metabolism and hunger.  Cortisol levels determine whether the body uses glycogen stores or triglyceride stores for energy (stored carbohydrate or stored fat).  Cortisol can also stimulate gluconeogenesis, the process of converting amino acids (proteins) and lipids (fats) into glucose in the liver.  It is believed that cortisol directly influences food consumption by acting on NPY neurons in the brain as well as affecting the levels of NPY and leptin.  Cortisol seems to have a particular effect on the desire to eat foods high in fat and sugar.  This is why stress management (which really means controlling any factor that might mess with your natural cortisol levels) is so important.

Glucagon is a hormone secreted by the pancreas when it detects low blood glucose levels (typically between meals, but this can also happen as part of that “sugar crash” after eating something very high carbohydrate).  Glucagon signals the liver to convert stored glycogen into glucose, which is released into the bloodstream, a process known as glycogenolysis.  When glycogen stores are low, high glucagon levels drive gluconeogenesis, the process of creating glucose from amino acids and fatty acids.  Increased glucagon amplifies the hunger sensation.

Insulin is secreted by the pancreas in reaction to high blood glucose levels (for more on insulin, see this post).  Insulin causes cells in the liver, muscle, and fat tissue to take up glucose (and fatty acids in the case of adipocytes) from the blood, storing it as glycogen.  While insulin is released as a result of eating carbohydrates, it paradoxically increases hunger as opposed to decreasing it.  This is caused by direct action on the NPY neurons and is the reason why eating a carbohydrate-rich meal is not as satiating as eating a meal that includes fats and proteins.  It also explains how quickly we feel hungry again after a high-sugar snack.

These hormones have important roles both in regulating aspects of digestion and signaling to the brain whether or not you need to eat.  Many of these hormones are also critical in regulating your blood sugar both after a meal and between meals (fed and fasted states).  Some of these hormones also affect other systems in the body, for example, interacting with the immune system and controlling inflammation.  Understanding how your diet and lifestyle affect these hormones will help you make choices that regulate these hormones properly, allowing yourself to listen to your hunger cues and trust that your body knows what it’s doing.  And regulating hunger hormones is a key part of healing and being healthy.

hunger hormones

Comments

Thank you for this post. I have Hashimoto’ s disease and I think I’ m used to being hungry most of the time because my blood sugar level must be imbalanced. I’m eating paleo since last summer and doing the AIP since last week, but hunger is still there (less that before, of course). Any advice for this? Best, Ana

I really think it’s important to eat fat, protein and some carbs (but not crazy on the carbs) at every meal. I’m going to be writing about the relationship between meal frequency and inflammation in the book (and probably a shorter version for a post), but the cliff notes are that it’s much better for resolving inflammation to eat three big meals a day, spaced 4-6 hours apart, rather than snack throughout the day. But, you don’t have to transition to that immediately. The trick is to get used to eating big enough meals that you can make it without snacking and at first that may seem like you are about to explode after a meal and that still isn’t enough. Your body gets used to it though. Work on eating a little more every time you have a meal and then try and get as long as you can before you need to eat again (feeling hungry is actually good for you, so it’s okay to feel hungry for a little while before you give in). Eating enough fat and protein will help with the blood sugar regulation.

I’m confused by the suggestion of spacing meals 4-6 hours apart. I have Hashimotos and this is contrary to recommendations of Dr. K and others knowledgeable in thyroid disease. I have experienced firsthand the inflammation and autoimmune attacks associated with larger, more infrequent meals. While eating Paleo AIP, I get weak and shaky if I don’t eat a snack 2-3 hours after a meal. I’m really curious to read your next post. You do have me wondering if I’m pre-diabetic or there’s something else going on with me causing these issues if I can’t get 4 hours between meals. Thanks for the great post :)

There’s a balance between optimizing hunger hormones and optimizing cortisol expression. The change from eating more frequently to eating less frequently should be done very very gradually to avoid cortisol spikes (why you often hear to eat more frequently with any illness that affects metabolism or something like adrenal fatigue).

I have Hashimotos, and used to have unstable blood sugar. The prime reason is eating carbohydrates by themselves. The very best blood sugar and hunger control comes from eating a moderate portion of protein, some root vegetable starch, some non starch veg and a little added fat together at a meal. I have about a palm of protein, like meat, 1/2 – 1 fist of starch depending on how much exercise I’ve done and 2 teaspoons or so of good fat like olive oil on my salad. Added to that – a big handful of green or coloured veg. This type of meal will keep me going at least 4 hours, often 6. I only need and get hungry for 3 meals a day. My weight is stable as is my blood sugar.

This article talks about how the memory of our last meal affects how hungry we are later. People who thought they ate a larger meal were less hungry than those who actually did eat a larger meal. A good case for more mindful eating to reduce hunger. Not that I don’t think the physical aspects (i.e. a balanced meal with fat) are not also important. I know from experience that a high carb meal will make me hungry faster and more intensely than a high fat meal but interesting nonetheless. http://www.scientificamerican.com/article.cfm?id=eat-less-by-altering-your-food-memories

As always, thanks for dropping the science. I learn so much here.

Hey Sarah, thanks so much for this great post! I’m curious if you could write a bit more about these hormones in relation to type 1 diabetes. (I too have hashimoto’s.)
I’m trying to get my A1C down from 7 but even with strict autoimmune paleo (for the last few months, started January with the 21-DSD) I’m still having a hard time keeping my blood sugars ‘even’.
I love these posts and I can’t wait for your book to come out!

Great post! I’ve been looking forward to these. Have you read Robb Wolf’s posts lately about the studies of carb partitioning…basically saving your carbs for dinner helped make people more leptin sensitive? I so look forward to learning more from you. Thanks!

Very interesting post Sarah! I have a very hard time with eating big meals. I get full pretty quickly,but then I’m hungry again soon. I tend to be more of a grazer then a big meal type. I don’t always have time for just sitting down for breakfast and lunch. So even with A.I.P & sugar detox I still nosh… could that be part of my problem with my inflammation still ? Because I must say I really am strict with what I eat, just not how often.I like d of eat little bits all throughout my day. I can also see how the brain contributes to the hunger process. I experience it myself. If I’m busy I tend to eat less then when I’m busy.
I learn just so much from you always. Thanks. Can’t wait for your book !!!!

I have been reading many of the articles that you have on this site and first, I really want to thank you for all the information you have here. I have been diagnosed with fibromyalgia, osteoarthritis (spine and shoulder), and iritis (so, I definitely have some inflammation issues). I also have chronic digestion issues (since childhood), that were significantly improved by a gluten-free diet. They never completely cleared, and now have been getting worse, so I’ve made the decision to start the AIP (I’m struggling with a few things, but I’ve decided to start… now just to figure out how!) Reading this article, I’m wondering how long it might take before my hormones stop being confused. I am literally never hungry right now, so listening to my hunger signals isn’t an option. Is there anything else I should consider (in addition to the AIP) to help out the healing process?

Yes, I would definitely look into taking some digestive support supplements. Digestive enzymes would be a great start. I would talk to a doctor about betaine HCl (stomach acid supplement, contraindicated for those with ulcers, blood clotting disorders or taking NSAIDs). And if you feel like digesting fat in an issue or have ever been diagnosed with gallbladder issues, you might also consider ox bile supplements.

The gallbladder isn’t considered an endocrine organ, but having it removed definitely affects digestion, which I guess could potentially change some of the more delayed hormones, although I haven’t seen any studies evaluating that. I hope you are taking ox bile supplements?

Thank you for this article! I am relatively new to understanding the consequences of my diet and have for about a year been eating paleo and trying to regulate joint inflammation and sugar reactivity. One ailment that I haven’t found an explanation for is ‘pounding in the ears’ or a type of throbbing. This generally occurs later at night when I would be craving sugars but there isn’t a direct correlation to how any carbs or sugars I’ve had. What causes it? Thank you in advance!

It’s not something I super familiar with and my understanding is that it’s due to increased blood flow (not necessarily high blood pressure although it could be, and stress can be a big cause too). Does it also happen when or after you work out? I’m wondering if it’s a stress response?

No! Working out helps actually. It began when we adopted Paleo and I think when my body was having a sugar craving. Its always worse with any increase of sugar in my diet and comes usually at night but sometimes I wake up with it. I posted here because of the conversation you began about the complexity of hormones and their interaction thinking it may be a known reaction. MY blood pressure has always been healthy but my liver suffered with pregnancies and I seem to feel stress more in my body. Thank you for your response!

Hi Sarah, as always, thank you so much for your excellent articles! I seem to have the opposite problem… I’m rarely hungry. Before on SAD I was NEVER hungry. I would have cravings and I would eat because it was “time”, but it had been years since I’d had a hungry feeling. Just by cutting out processed foods and poor fats, I started to get hungry. Now that I’ve been Paleo for 3+ years and AIP for over 2, I’m back to rarely being hungry. Some mornings I wake hungry, but not all. If I eat a smaller breakfast, then I’ll get hungry mid-morning. But I’m rarely hungry for dinner. Any thoughts? Thanks so much!! Keep up the great work.

Lack of appetite is common, especially in thyroid patients (hi MomLady!). It becomes even more important to choose very nutrient-dense foods like offal and seafood over less nutrient-dense foods when you are not eating as much, and adding healthy fats like coconut oil to meals can help sneak in extra calories if you are losing too much weight. Hopefully, increasing the nutrient-density of your meals and eating regularly (even if its only a small amount) will help your body sort out its appetite. – Christina, Sarah’s assistant

Hey Christina!! I’ve been tolerating AIP “treats” and I think I’ve gone too far with them. Need to get back to the basics again. Thanks for the reminder! :)

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