How Inflammation Affects Our Hypothalamus and Hunger Response

Written By: Kevin Cann

            Our lifestyles are much different than those of our Paleolithic ancestors.  Our ancestors had to worry about predators, food shortages, and droughts.  They had plenty of down time to relax and unwind and had to be active to forage for food.  Currently, none of this applies.  The only predators that we need to worry about are locked up in a cage in a zoo and food is found at super markets that are easily accessible via automobile.  This does not mean that our stress levels are lower than those of our ancestors; in fact our stress levels are much higher and is it a coincidence that our rate of obesity is also much higher?

On a day to day basis we deal with stressful things such as shortened sleep periods, traffic, bosses and coworkers, family and relationship issues, worries about money, health, health of family members, etc.  Our stress response has not had the time to adapt to this list of constant and chronic environmental stressors.  Identifying when these stressors are affecting us and finding optimal ways to manage these stressors are keys to our health and well-being.  Also, not adding stressors such as overtraining, eating gut irritating foods and overeating are also key components to maintaining a positive quality of life.

Environmental stressors cause a reaction in our bodies.  Inflammatory cytokines are released and this can be detrimental to our health.  Inflammatory cytokines suppress our body’s ability to defend itself from outside pathogens.  They can also cross the gut-brain barrier and influence infectious, auto-immune, and allergic diseases (Elenkov, 1999).  One of the biggest culprits of this is the inflammatory cytokine interleukin-6.

IL-6 actually interferes with the liver and causes a build-up of the glycoprotein, fibrogen in the blood.  This increases the thickness of our blood.  Along with this we get an increase in serum amyloid A, a group of proteins associated with our HDL in our blood.  This increase in serum amyloid A leads to a decrease of HDL in our blood.  The increased thickness of blood and the decreased HDL can lead to arthrosclerosis, but that is a story for another day.  The IL-6 can also interact with our hypothalamic-pituitary-adrenal axis (HPA) and this can lead to insulin resistance and obesity (Yudkin, 1999).

Our hypothalamus is the part of our brain that controls our hunger response.  Leptin, and to a lesser extent, insulin are controlled from this section of the brain.  Inflammatory cytokines can cross into the hypothalamus and induce leptin and insulin resistance, which then can lead to weight gain.  One major cause of this is overeating.  Our cells have an energy limit that is preset.  Anything more or less can be detrimental to our bodies.  When excess food intake is introduced to our bodies we react via cellular inflammation.  This inflammation causes a down regulation of leptin and insulin receptors.  Both leptin and insulin are important in weight control.  Leptin signals to our brain how much body fat we need to store and insulin stores the body fat in response to what leptin tells our brains.  When the down regulation of receptors occurs our hypothalamus goes into a protective, starvation mode and increases our appetite and decreases our willingness to exercise.  This leads to weight gain, which then leads to increased leptin in the blood, which leads to more weight gain.  Eventually we reach obesity (Wisse, 2009).

Food selection becomes another critical component as well as balancing the omega 6:omega 3 ratio.  Certain foods can actually shut off our body’s way of telling ourselves we are full.  They elicit a response from dopamine and serotonin and this makes us feel good.  They also elicit a response from cannabinoids that make us crave these foods (For more information on this topic read my past posts on Carb Addiction, and Food Addiction).  This can lead to overeating which causes the inflammatory response mentioned previously.  This is why “everything in moderation” is an unsuccessful tactic in most cases.

Finding ways to manage our everyday stress and eating a paleo diet are keys to mitigating the inflammation response that can lead to so many negative health outcomes.  Studies have been done on some alternative health therapies and inflammation.  Behavioral therapy, hypnosis, mediation, acupuncture, and biofeedback have all been shown to have anti-inflammatory effects through stimulation of the vagus nerve, the nerve that connects our brain to our gut (Tracey, 2002).  If weight loss is your goal it is imperative that you handle your stress, and the inflammation that comes with it.  If you don’t, you may just be wasting your time and effort on diet and exercise.



Tracey, Kevin (2002).  The Inflammatory Reflex.  Nature Publishing Group.  Retrieved March 23, 2012.

Wisse, Brent (2009).  Does hypothalamic inflammation cause obesity?  Cell Metabolism.  Retrieved on March 23, 2012.

Yudkin, John (1999).  Inflammation, obesity, stress, and coronary heart disease; is interleukin-6 the link?  Retrieved on March 23, 2012.

Elenkov, Ilia (1999).  Stress hormones th1/th2 patterns, pro/anti-inflammatory cytokines, and susceptibility to disease.  Retrieved on March 23, 2012



Kevin is owner of Genetic Potential Nutrition. He is a holistic nutritionist, wellness coach, and strength coach. He works with people fighting illness, to competitive athletes. Check out his site at

Categories: Anti inflammatory diet, Weight Loss


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  1. Mat says

    The assertion that paleolithic lifestyle was less stressfull than modern life is incredibly misled. Modern worry is about status, long term health and not much more, mostly blown out of proportions by people who simply dont know the feeling of real threat any more. Confronting this with the daily possibility of a brutal death by predators, both man and animal, famine and incurable desease shows how much of a romanticisation of paleolithic life happens in this post and in the general community. If anyting, we are blessed to live in this day and age and to say otherwise speaks of a less than realistic point of view.
    Today, we have a chance to take the good parts out of paleolithic life and apply it to ouselves. Our ancestors didnt have a choice, they simply struggled to survive.

    • says

      So…all that stuff about the “original affluent society” from the anthro circles is just bullocks? I believe you are missing a critical distinction between chronic and acute stress. but I digress.

    • says

      I agree with Mat, not me by the way. Neurotic and obsessive thoughts always find something to stress about. Most of our worries are imaginary, and most of the things we stress about today could have been stressed about in the Paleolithic era. Status, power, sexual affairs, and general social stressors. Worry about starvation and attack by man or animal. Those are chronic stressors.

      Does stress cause inflammation? No. Cortisol is extremely anti-inflammatory, so if anything, stress is anti-inflammatory.

      And if stress is a central cause of leptin resistance and obesity, then why did everyone start becoming obese in the 1970’s? Did stress suddenly sky-rocket?

      I think you would have been far better off sticking with an inflamed gut as the leading cause of inflammation, as that would have been far more accurate.

      It also seems that the premise of this article is not supported by any good scientific literature. The Wisse study you cited AND the related study I link to below, both name a high fat diet as the culprit of inflammation. I don’t know what animal they were studying that led them to that conclusion, but it must not have been humans, because that is just plain false, and I believe it is intentionally misleading. If you need further convincing that fat is not anywhere near as inflammatory as, say a bowl of Corn Flakes, just email me through my website.

  2. Martin says

    Sapolsky’s “Why Zebras Don’t Get Ulcers” addresses the stress issue in great detail: the stress we experience today is chronic but typically not acute. Wild animals, on the other hand, and probably our ancestors, at least till they developed brains big enough to start worrying about how events from the past might impact the future, typically experienced lowel levels of daily stress, with occasional periods of very acute stress when they literally fought for survival. According to Sapolsky chronic stress is worse.

  3. Martin says

    The stress / inflammation / hunger story seems to be addressing the old ‘brain vs cells’ question (Gary Taubes writes a lot about it): is it our brain that controls hunger (and thus weight gain / obesity) (set point and food reward theories fall in this category) or is it due to peripheral processes (e.g. insulin’s effect on cells).

    Regarding the meditation / relaxation part (which I take very seriously and I’m trying to practise on a daily basis): let’s take a group of healthy, stress-free individuals on a perfect paleo-diet, living a balanced, relaxed, etc. life and feed them lots of sugar. Would they NOT develop insulin resistance leading to obesity and metabolic syndrome?

  4. says

    I agree that Paleolithic times are often falsely portrayed as idyllic and stress-free. That said, I also believe (like Robb) that modern, chronic stress is especially harmful because it’s coupled with a sense of alienation and social isolation that our ancestors likely did not experience. Humans lived in small groups and extended families for the vast majority of our evolutionary history (and still do in many parts of the world), and the consequences of departing from that norm are arguably as significant as the effects of adopting a modern diet.

    • Cheryl White says

      Do you think that extended social isolation could create a sort of feed-back loop in which individuals actually lose the desire to socialize? It seems to me that isolation in and of itself creates an atmosphere in which it’s far too easy to make bad decisions.

      • Amy B. says

        In my experiment of n-1, yes, this can happen. (And it has–> to me.)

        For a number of reasons, I’ve spent a TON of time by myself over the last several years. I’ve always been an introvert, but I’ve noticed lately that being with other people drains me a lot more than it used to. I think in some ways I’ve become so used to my own company that I have little to no tolerance/patience for things that aggravate or annoy me, which, it turns out, are other people. In particular, people who are physically incapable of sitting still or being quiet for five whole minutes. (Fidgeting, whistling, jingling the change in their pockets — I sit in a very high-traffic area in my office and I’m sort of surrounded by people all day. The constant movement and general low level “noise’ drives me nuts.)

        I get very lonely sometimes, and it’s a bummer when I don’t *want* to be alone. But there are other times when I finally join the rest of humanity and go out, and I usually wind up *wishing* I was back home, alone. (Or at least someplace quieter.) Maybe I’m just becoming an old curmudgeon before my time…only 33 yrs old. The LAST place you will ever find me is “opening night” at some flashy new restaurant, or standing in line overnight for tickets to the “must see” show or whatever. I generally avoid crowds and hullabaloo as much as possible.

        • says

          Sounds like you are far on the introvert side of the scale via Meyers Briggs. Just describes how you get energy. I tend to be on the extrovert side a bit. Nothing odd about this, just need to find a no -fidgety peer group!

          • Amy B. says

            Hehheh…yeah, MAJOR introvert. I’ve always been this way, but it seems to be getting stronger.

            INFJ last time I did a Myers Briggs, but that was a few years ago. (Maybe today would be a good day to take one again…and distract myself from all the noise.) 😉

          • says

            AH! And the J part is all about “rules”. REALLY good at details! Yea, Amy, I think you just need to sniff around and find a group that fits. And there will ALWAYS be some coat/benefit to the story, but I think you can find something that is good as you need and you can pull the rip-cord and jump out once you’ve had your people quota.Keep me posted on this, I’m interested.

  5. brandon says

    Read, Why Zebras Don’t Get Ulcers – Robert Sapolsky. Its not romanticised, its a matter of timing. Short term vs. long term. (i.e chronic vs acute)

  6. tami says

    help? i’ve been on the paleo diet going on 3 mos now. my intention was not to lose weight, which i have lost about 8# which i’m not sure i can afford. it was very easy for me to make this food change and i am stoked that i haven’t had a migraine since i quit eating grain. as i’m dead in the of menopause & found my horrormone balance all over the map prior and now i don’t even feel like i need to take my horrormones anymore (tho my husband, a holistic MD thinks it’s important to stay on them-biodenticals). the ONLY thing i’m struggling w/is LACK of strength and energy. i USED to be extremely active, but now it exhausts me to climb a few steps. (2 summers ago i hiked 2 14Kr’s in 1 day, retired firefighter, country girl type) what can you tell me about this ‘problem’ which it really is for me thx

    • Amy Kubal says

      Tami! Make sure you are eating enough and maybe experiment with adding some starchy carbs (yams, sweet potatoes) especially post workout if you are working out! Also, how’s your sleep? Keep us posted and please let me know if you’d like some help getting this figured out!

  7. says

    While I’m not anthropologist, I feel that the stress response in indigenous cultures, which I assume to be representative of our paleolithic ancestors is much different than mine and what I assume to be the average westerner’s. If you have not I would recommend Frank Marlowe’s book “The Hadza” which is an ethnography of the Hadza hunter gatherer’s in Tanzania. The social structure is in some ways very obvious but the lack heirarchy or religion to me are just counter to my assumptions of “primitive” cultures.

    While it’s not stated in Marlowe’s book it does seem to me, based on various documentaries I’ve seen, that indigenous cultures seem to have a very limited anxiety. I recently watched a Kung hunt where a man crawled into a small burrow after two large porcupine. I feel certain he was aware of the risk involved but showed no trepidation in doing it. Similarly I saw a hunt in Papua New Guinea where a hunter dove into a burrow to chase something his dog had cornered, it wasn’t even clear what he was chasing, but again no trepidation.

    Perhaps I’m just overly anxious (entirely possible) but I’m left with the very distinct impression that even accute stress and the specter of injury or death is not internalized the same way in many cultures as it is in western ones. I cannot believe this is due to a lack of foresigth or imagination. In cultures, such as the Hadza, with no afterlife theology this is even more mysterious as the permanence of death does not seem to be at all in question.

    While we surely have created a social and physical environment different than contemporary or ancient hunter gatherers I’m left to think that our concern (or internalization thereof) over our demise (it’s why we care about paleo after all) does not appear to me to be common amongst all cultures.

    Perhaps the stress states of these people are really so fundamentally different they we cannot discuss them with any reference to our own.

  8. Samantha says

    I went on a very low carb diet in 2010. I stayed on it for a year, despite the fact that it caused intense hypoglycemic symptoms (it brought my missing period back, so I trudged on). In 2011 I went off the diet and added carbs back in. I felt great and had a normal appetite again and lost the 20 pounds the near zero carb diet had packed on. A couple months later though, without changing my carb intake, it was like something broke in my body and the hypoglycemic symptoms returned with a vengeance. I’m on a moderate carb Paleo diet for over a year now, but have gained 25 pounds and am ALWAYS hungry. It keeps me awake at night and generally miserable. Bloodwork is mostly normal and endocrinologist can’t do anything. I think I damaged my hypothalamus. Any ideas? Please? This is really a nightmare.

  9. Elle says

    To Matthew Caton, stress is NOT antiinflammatory. All kinds of stress, regardless of whether its a psychological stress, or a physical stress induce increases in proinflammatory cytokines. And yes, glucocorticoids are produced, which can inhibit the release of these cytokines and thus have an anti inflammatory effect. However in the case of chronic stress, where there is prolonged secretion of cortisol, immune cells become desensitised, and cortisol can no longer modulate inflammation. Stress is absolutely not anti inflammatory. Inflammation can also activate the stress response, which leads to further inflammation. This is why stress is associated with accelerated cellular aging, cancer, heart disease, and metabolic issues.

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