Hunger and Satiety Hormones

July 7, 2020

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ghrelin leptin hunger satiety hormones Today we’re taking a peek under the hood and looking at some of the hormones involved in hunger and satiety, a.k.a. appetite hormones.

You might think of hunger as a gnawing feeling in your stomach and satiety as that feeling of fullness when you’ve eaten enough… or maybe too much. That’s how we experience the feelings we call hunger and satiety, true; but I’m talking today about the physiological drives to eat or stop eating that is driven by hormones.

Eating behavior is coordinated mostly in the brain by the hypothalamus, which acts as the control center for appetite. Hunger and satiety hormones deliver information from the body about how much energy you are taking in and whether you need more. The overarching goal here is energy homeostasis—balancing the energy coming in (via food) with the energy needed for the everyday functions of being alive.

When you have sufficient energy, your body is free to invest in growth, repair, and reproduction. Taking in more energy than you need can lead to excess fat storage and issues like hyperinsulinemia, insulin resistance, and metabolic syndrome. Energy deficits result in adaptations designed to conserve energy. In the long run, energy deficits might increase longevity, but they can also seriously undermine health and, for example, impair fertility.

Today I’m going to cover some of the key hormones that are involved in this delicate dance. This is by no means a complete list. Let me know in the comments if you have a burning desire to learn more about one of the hormones not covered here.

Ghrelin: the Hunger Hormone

Ghrelin is usually called “the hunger hormone” because it directly stimulates your drive to eat. In fact, it is the only known peripheral (outside the central nervous system) hormone that has this effect. Other peripheral appetite hormones all act to suppress hunger and reduce food intake. I always use the mnemonic “ghrelin gets your stomach growlin’” to keep it straight. I’m sure the endocrinologists in the crowd are groaning at that one.

Ghrelin is released primarily by cells in the stomach. Levels rise before meals and correlate with subjective feelings of hunger.¹ It also activates reward centers in your brain so that food is more appealing, and your motivation to eat is stronger.²

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Should I Just Take a Ghrelin Blocker?

After it was discovered in 1999, ghrelin became a target for drug companies hoping to cash in by developing ghrelin inhibitors as a treatment for obesity. These efforts haven’t panned out for several reasons. First, ghrelin doesn’t stimulate overeating in normal physiological conditions. If you administer ghrelin to a human or lab rat, they will eat more, even to the point of becoming obese in the case of rodents. Normally, though, ghrelin levels don’t stay consistently high. They rise and fall to reflect energy balance. After you eat, ghrelin levels fall in proportion to the number of calories you ingest,³ and more strongly in response to eating carbs and protein, compared to fat.⁴

Ghrelin doesn’t stimulate eating just for the heck of it. Its main job seems to be preventing a negative energy balance. Obese individuals actually have chronically lower ghrelin than their lighter counterparts.⁵ On the flip side, individuals with anorexia or cachexia due to chronic illness, who are in a severe state of negative energy balance, have high circulating ghrelin levels.⁶

Drug trials have also been stymied because ghrelin has wide-reaching effects on other aspects of health besides eating behavior. Some of the known activities of ghrelin include:⁷ ⁸ ⁹

Stimulating growth hormone release, which among other things helps regulate blood glucose levels during prolonged fasting or starvation¹⁰
Increasing insulin sensitivity
Improving cardiovascular function
Promoting muscle growth and bone formation
Regulating stress and anxiety
Suppressing brown fat thermogenesis, contributing to energy conservation

In other words, suppressing ghrelin could be very costly indeed. You can focus on metabolic flexibility instead. More on that later.

Leptin: the Satiety Hormone

Leptin’s main job is to signal to the brain when you have sufficient energy available. It is produced by adipose (body fat) cells. More body fat means more circulating leptin. Leptin is also released after you eat. Carbohydrate intake prompts a particularly strong leptin response, protein less so, and fat probably only minimally.

Sometime leptin is characterized as ghrelin’s counterbalance. Whereas ghrelin is “the hunger hormone,” leptin is “the satiety hormone” (although in truth there are many, as you’ll see). If ghrelin tells the brain GO, leptin tells the brain STOP. I think that characterization isn’t exactly correct, though.

It seems to me that both leptin and ghrelin prevent negative energy balance. If you think about it, for most of human history, energy shortage—which, in the extreme, means starvation and death—was a much bigger problem than energy abundance. Consuming too much food is a thoroughly modern problem. We should be more strongly attuned to shortages.

Elevated ghrelin levels signal to the brain that it’s in danger of going into the red; low levels of leptin do the same. This explains why low leptin is particularly problematic from a health perspective. It’s associated with mood disturbances and infertility, among other issues.¹¹ ¹² Low leptin and high ghrelin both put the body in an energy conservation state. Leptin decreases, and ghrelin increases, in response to dieting and weight loss.¹³ ¹⁴ In fact, leptin decreases more than you’d expect just based on how much body fat is lost while dieting. It’s one of the reasons hunger increases and can become unbearable when you’re on a diet. Presumably, these hormonal changes reflect the body’s efforts to defend its energy stores and restore homeostasis.

As with ghrelin, leptin’s functions extend well beyond appetite. Leptin has a hand in bone and cardiovascular health, insulin sensitivity, regulating thyroid hormones, insulin sensitivity, and glucose metabolism.

How to Increase Leptin Levels

It is possible to increase your leptin levels naturally, without medication. Here’s how to do it.

Eat enough food. If you are severely depriving yourself, leptin will be suppressed and ghrelin will take over. That’s no way to live.
Be sure to get healthy fats. Fats signal to your body that you’ve consumed enough calories, and they take longer to break down than carbs do. Some of my favorite sources of healthy fats include avocado oil, coconut butter, ghee, and macadamia nuts, among others.
Restrict carbs for a time. Carbs need to be constantly replenished. Once you get past the “low-carb flu,” you’ll find that you have energy without constantly having to reach for snacks.
Cycle in carbs. To optimize your leptin and ghrelin balance, you’ll want to achieve metabolic flexibility.

For more details on leptin and how to control it, read this article.

Neuropeptide Y

Neuropeptide Y, or NPY, is the most abundant peptide in the central nervous system. Found mostly in the hypothalamus, it acts as a hormone and neurotransmitter. It’s involved in a host of actions locally in the brain and throughout the body.

Most importantly for the present purposes, NPY is considered the most potent appetite-stimulating compound in the human body. Each of the other hormones discussed in this post regulates food intake by acting on NPY in the hypothalamus. For example, ghrelin increases NPY activity, while leptin suppresses it. Elevated NPY strongly increases the drive to eat, especially carbohydrates.¹⁵

NPY acts to maintain energy homeostasis by decreasing energy expenditure, movement, sex drive, and thermogenesis when needed.¹⁶ It’s also expressed by fat cells, and research suggests that NPY promotes fat storage.¹⁷

Another potentially exciting area of research is examining the role of NPY in aging. NPY is important for coping with and adapting to stress,¹⁸, and it has known neuroprotective effects. There are a number of reasons to think that NPY is the key that explains how caloric restriction extends lifespan.¹⁹ I’m keeping my eye on this.

Peptide YY

Peptide YY (PYY) is produced in the intestines after you eat. It travels through the bloodstream to the hypothalamus, where it inhibits NPY, decreasing appetite. PYY also modulates other digestive functions, including pancreatic and gallbladder activity.

The amount of PYY produced is proportional to the number of calories consumed. Studies find that higher-protein meals cause the greatest rise in PYY, followed by higher-fat meals. Not only do high-carb meals stimulate the least PYY, PYY peaks and then starts to decrease quickly after high-carb meals, whereas it continues to rise for hours after meals containing more fat and protein.²⁰ This may be one reason you don’t stay full for long after eating high-carb meals.

Cholecystokinin

Cholecystokinin (CCK) was the first known satiety hormone. It is secreted in the gastrointestinal tract, especially in the small intestine. CCK rises quickly after eating, especially in response to fat and protein in the meal, and it triggers the initial release of PYY.

Like PYY, CCK is involved in various processes related to digestion, especially the digestion of fat. CCK also has interesting effects in the brain. The hippocampus contains a large concentration of CCK receptors, indicating that CCK plays an important role in learning and memory, though it’s still not well understood.²¹ High levels of CCK are related to anxiety and panic attacks, while schizophrenic patients may have abnormally low levels of CCK in their brains.²²

Glucagon-like Peptide-1

Abbreviated GLP-1, this hormone is secreted by the ileum and colon in response to nutrient intake. It acts as a satiety hormone, but researchers are especially interested in how it stimulates insulin secretion, improves insulin sensitivity, and helps regulate blood glucose.²³ GLP-1 figures prominently in experimental treatments for type 2 diabetes.

Following bariatric surgery, patients’ GLP-1 and PYY increase significantly, which probably accounts for post-surgical reductions in appetite,²⁴ which can persist for decades after the procedure.²⁵ Research using a rat model also suggests that GLP-1 facilitates the rapid metabolic improvements that often follow surgery.²⁶

Insulin

Let’s end with a familiar one. You probably know that the pancreas releases insulin after you eat, especially following carbohydrate intake. Insulin is sometimes called the “storage hormone” because one of its main jobs is to “unlock” adipose cells in order to store fat for future use. In healthy individuals, it also supports energy homeostasis by inhibiting lipolysis (fat burning) when there is sufficient glucose in the bloodstream to supply energy.

As with the other hormones discussed here, insulin also acts as an energy barometer for the brain. It crosses the blood-brain barrier, where it regulates NPY expression and suppresses appetite.

Can You Control Your Hunger Hormones?

It’s tempting to think that if we understood these hormones’ actions, we could learn to control hunger and eating behavior and solve all the problems related to overeating. As great as that sounds, we’re a long way off.

As you can see, energy homeostasis depends on the coordination of many different signaling pathways within the body. Too often, people try to hone in on the effects of just one variable—leptin or ghrelin, say—hoping to manipulate hunger and satiety. None of these hormones works in isolation, though. There is still a lot to learn about the physiological significance of each of these hormones individually, not to mention how they work in tandem with one another.

Furthermore, in human studies, hormone levels don’t consistently map on to our actual eating behavior as you’d expect. This might be because scientists haven’t uncovered the whole picture and don’t understand how all the various pieces work together to produce hunger. Probably, it’s also because we humans are complicated creatures who eat for a lot of reasons other than pure physiological hunger.

What does it all mean? I think it means don’t look for a magic pill that will allow you to control appetite and hunger. If you struggle with unwanted hunger, the first thing to ask is whether you are eating enough to meet your energy needs. Are sending your brain scarcity signals by not eating enough, or perhaps not often enough? That’s an easy fix.

Next, you can try manipulating your macros. One of the advantages of low-carb, high-fat (LCHF) diets over low-fat, high-carb (LFHC) diets is that appetite is managed much better on LCHF.²⁷ Protein is also quite satiating, likely due to the actions of hormones like ghrelin and PYY.²⁸ If you go very low-carb, you might experience the appetite suppressing effects of ketosis as well.

Check in with your stress levels and sleep habits. Too much of the former and not enough of the latter can drive up appetite.

If none of those is the answer, it might be time to make an appointment with an endocrinologist or functional medicine practitioner who can help you dig deeper.

Hunger isn’t something to be avoided, though. Hunger and satiety are normal physiological signals. Their job is to keep us alive and thriving. Rather than trying to manipulate or hack hunger, it’s useful to understand where it comes from so that we can respond appropriately and have the energy we need to be active and healthy.