The Hypothalamus: The Mystery of Cravings

We are making progress in our research and conversations of the disease of overweight/obesity, but there are still huge, gaping holes and I think the role of the hypothalamus fills one of them. Let’s talk hypothalamus today!

The hypothalamus is an area of the brain that controls hormones to maintain homeostasis, or equilibrium. It is here where there is a system to move most physiologic parameters in whichever direction is needed to keep them within the normal range, such as temperature, heart rate, and, you guessed it, body weight. For example, the hypothalamus can raise or lower body temperature, raise or lower thyroid hormone level, and raise or lower body weight. Let’s look more closely at how the hypothalamus regulates body weight so we can see how it may go awry and what we may be able to do about it.

Hypothalamic Regulation of Energy Homeostasis

The hypothalamus is in charge of regulating energy input and output for the purpose of maintaining a body weight or body fat set point. It does this in a few ways:

Resting metabolic rate: this is the metabolic rate at rest. This goes up if your body weight is lower than your hypothalamus thinks you should be, and it does down if your body weight (or body fat stores) are lower than your hypothalamus thinks they should be. This is a large part of metabolic adaptation to weight loss which shows metabolic rates are lower for a given body weight after weight loss. For example, a person who naturally weighs 180 pounds with a 25% body fat will have a higher resting metabolic rate than someone who naturally weighs 230 pounds and lost 50 pounds through diet and exercise and ended up with the exact same 180 pound body weight with a 25% body weight. This is because the person who lost 50 pounds has a hypothalamus that “thinks” 230 pounds and a body fat that is likely closer to 35% is “normal” for that person. Conversely, if a person gains weight, the resting metabolic rate will increase until the weight returns to “normal” also.

Hunger & Cravings: the hypothalamus also drives a person to a weight set point by increasing or decreasing hunger and cravings. There are 2 sets of hormones: orexigenic hormones which increase hunger and the drive to eat, and anorexigenic hormones which decrease hunger and the drive to eat. When body fat and body weight are lower than a weight set point, as happens after weight loss, orexigenic hormones increase and hunger and cravings are increased. This is happening at the same time that the resting metabolic rate has slowed. Other things that increase orexigenic hormones are sleep deprivation and stress. Eating a meal decreases orexigenic and increase anorexigenic hormones. This is why eating at regular intervals can reduce hunger and cravings.

The above descriptions apply to the normal function of the hypothalamus. However, there is more research into how a high fat diet and the state of obesity can cause abnormal hypothalamic function and uncouple the normal hormones of the hypothalamus from body weight and body fat regulation. This is another example of how the cycle of obesity can fuel worsening of the condition. As the hypothalamic function is uncoupled from actual energy status of an individual, the normal function of regulating energy and body weight does not work properly. Let’s look more closely at how a high fat diet and/or the state of obesity can cause abnormal hypothalamic function and how that can affect a person.

Short Term Effect of High Fat Diet Feeding - Cravings, Explained?

Studies show that it takes only three days of high fat feeding to cause reduced sensitivity to insulin secretion and leptin and an inflammatory state in the hypothalamus. An important principle of normal hypothalamic function is that it relies are normal cyclical nature of feedback. In food and body weight, this means that normal hypothalamic function relies on cyclical rising and falling of eating. When energy intake is higher than normal and more persistent than normal, it stops responding normally. An analogy is when someone keeps yelling at you, the natural reaction is to “tune them out”.

Fatty acids, especially saturated fatty acids, cross the blood-brain barrier, accumulate in the hypothalamus and cause inflammation and blunt anorexigenic signaling by insulin and leptin and promote positive energy balance (weight gain). This may be why just a few “cheat meals” can make a person feel poorly and crave more “comfort food.” Monounsaturated fatty acids did not impair hypothalamus function.

Chronic Effects of High Fat Feeding

If it takes only three days of high fat feeding with saturated fatty acids to induce brain inflammation and resistance to insulin, leptin, and other anorexigenic hormones, what happens with more long term eating with this pattern? Obesity is recognized as a chronic inflammatory state. This is likely, in part, because fat stores outgrow its blood supply. The inflammatory mediators released affect the neurons in the hypothalamus as well. This is another mechanism by which hypothalamic function can be altered from normal and energy regulation is uncoupled from body weight and body fat stores. The chronic inflammatory state and chronic high fat feeding can also alter the central nervous system’s ability to repair damage. This may be why obesity is associated with neurodegenerative conditions.


There is growing evidence that consumption of high-fat, high-carbohydrate diet is associated with hypothalamic deregulation in the human brain. This may also affect the fetus when it happens during pregnancy. New recommendations address proactively treating excess weight during the childbearing years because of the potential to affect “epigenetics”. What does this mean in real life? Well, this may be why it is so hard to get back on plan after that all inclusive vacation, and why it may feel like your "stomach has shrunk" after a few months on the program and that you do not want to eat as much as you used to. This may give you information as to why it may be more precarious to go "off plan" completely for that weekender or vacation. If your hypothalamus gets inflamed and your anoregixenic hormones become uncoupled from your energy intake and your leptin becomes unsuppressed, then it may be a slippery slope!

One of the reasons for doing a very low calorie diet instead of a simple calorie deficit diet is that magnitude of intervention may be more likely to restore the normal hypothalamic function and coupling of homeostatic mechanisms.

So, when someone says, “It is all in your head,” remember the hypothalamus!

Take Back Your Health,

Valerie Sutherland, MD

For more information, read here.

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