Written by: Kevin Cann
Leptin is a hormone that was discovered in 1994. It plays a critical role in energy homeostasis, hunger, satiety, and behavior. Leptin is released from our white adipose tissue and communicates with the brain regarding how much fat we have in storage. When this system is working properly along with the other energy homeostatic hormones insulin, glucagon, and adrenaline, our weight remains at a healthy level.
Under normal circumstances we seek out food when leptin levels are low, and should be satiated when leptin levels are high. Leptin also follows a circadian rhythm. Levels should be low in the morning, stimulating us to eat, and they should be high in the evening, with the lowest levels around noon and the highest after midnight (http://www.google.com/url?sa=t&rct=j&q=&esrc=s&frm=1&source=web&cd=9&cad=rja&ved=0CGUQFjAI&url=http%3A%2F%2Fhrcak.srce.hr%2Ffile%2F44314&ei=ApdMUr2_Kozi8gT86oHABA&usg=AFQjCNEN0hed7rHDC_ZLHnG49i3gEyVqbw ). It is unclear the reasons for this rhythm, but blood sugar control may be the issue. Leptin’s rhythm is in direct opposition to cortisol’s daily rhythm. In fact the glucocorticoids associated with our fight or flight response may play a modulatory role in leptin synthesis (http://www.ncbi.nlm.nih.gov/pubmed/11824503 ). This means that if we do not manage our stress we can put ourselves in a dysfunctional leptin rhythm.
Just like with insulin and adrenaline, as leptin levels rise, our leptin receptors become desensitized to the hormone and we can develop leptin resistance. This means when our white adipose tissue sends the signal to our brains telling us to stop eating, our brain does not hear the message and we continue to eat. Dysfunction in the circadian rhythm of leptin can directly cause leptin resistance (http://edrv.endojournals.org/content/31/1/1.full ) as can eating a diet high in processed foods (http://www.ncbi.nlm.nih.gov/pubmed/21418711 ).
Leptin may actually be the major player in the metabolic dysfunction that causes obesity, as it is tied to a number of different hormones responsible for weight gain and disease. Leptin may play a role in the pathophysiology of thyroid dysfunction with the regulation of uncoupling proteins (http://www.eje-online.org/content/149/4/257.full.pdf ). It even has been theorized to play a role in the formation of cancer (http://www.ncbi.nlm.nih.gov/pubmed/16110483 ). One area that I find to be extremely interesting is the role that leptin plays on dopamine.
Dopamine is our hunt and reward neurotransmitter. It is responsible for memory, focus, and energy levels. Dysfunction in the dopamine pathways has been implicated in neurodegeneration, ADD, ADHD, and various mood disorders such as schizophrenia. Dopamine is also a popular target for addictive drugs such as cocaine. Dopamine also plays a critical role in our drive to eat.
The dopamine response to overeating is very similar to that of addictive drug behavior (http://www.nature.com/neuro/journal/v13/n5/full/nn.2519.html ). Processed foods can elicit a greater reward response than fruits and vegetables. For example, can you eat more broccoli or ice cream? This increased influx of dopamine can cause our cells to become desensitized to the neurotransmitter. According to Dr. Kenneth Blum’s Reward Deficiency Syndrome, we will become addicted to anything that balances out our biochemistry. If we are dopamine deficient and eat foods that raise dopamine levels enough to balance us out, we will become addicted. Even with adequate levels of dopamine we can be in a deficient state due to the desensitization of receptors. If we become desensitized to dopamine, we will need to eat more of these foods to elicit the same balancing act.
Leptin communicates directly with dopamine pathways. Leptin may raise dopamine levels enough to make it easier to resist rewarding foods. Remember according to Dr. Blum if we are deficient in a neurotransmitter we will seek out foods and substances that balance us out. Leptin can help us avoid this situation. However, if we are leptin resistant our dopamine levels may become deficient and we will crave sugary foods. Leptin injected into the dopamine center of the brain has even been shown to cause rats to eat less and lose weight (http://www.news-medical.net/news/20090805/Leptin-influences-baseline-dopamine-levels-and-motivation-to-eat.aspx ).
In my practice I use questionnaires to determine neurotransmitter deficiencies, and almost everyone has a deficiency in dopamine. There are many factors that play a role here, but leptin resistance is one that cannot be overlooked. This may also be one way how leptin could be implicated in certain mood disorders and addictive behaviors. Low levels of leptin have been associated with depression (http://www.ncbi.nlm.nih.gov/pubmed/18032111 ). This may explain why treatment with specific amino acids and anti-depressant medications do not have a 100% success rate. Mood may not be able to be improved in the presence of leptin resistance. This makes proper nutrition, exercise, and lifestyle behaviors even more important when treating mood disorders and other diseases. It also shows us how little we truly understand in the dynamics of disease.
Leptin being a relatively new discovery makes it difficult to truly understand. The more I research it the more I feel it may be the major player in metabolic control. Spacing meals out five hours apart, getting adequate sleep, having good vitamin D levels, and managing stress can all have positive effects on leptin. As we learn more about this powerful hormone we can develop better treatment protocols to get it back on track.
Also be sure to check out my previous post on how meal frequency affects leptin levels here: http://robbwolf.com/2013/07/18/meal-frequency/ .
Thank you for this great article! I’m convinced by your explanation of the mechanism behind addiction, since it matches perfectly my own view on our body and mind – we need our essential substances to feel good (for the machine to work properly), and any disbalance here throughs us out of balance.
Have you heard about the work of Dr. Jack Kruse and his Leptin reset protocol? Check http://www.jackkruse.com.
Great article, fun read. Leptin is also starting to look like a major regulator of inflammation via the activation of the mTOR pathway in lymphocytes, which pushes them towards activated, glycolytic metabolism, in contrast to adiponectin, which is secreted in inverse proportion to leptin by adipose tissue, and activates intracellular AMPK signaling, promoting oxidative metabolism and tolerance (non-response) in lymphocytes.
Cells of the immune system are accustomed to oscillatory mTOR signaling, presumably because of the circadian rhythm of leptin secretion, and chronically activated mTOR in lymphocytes is a key feature of chronic inflammation. So, another feature of chronically elevated leptin like you mention above is the promotion of chronic inflammation, dominated by glucose-based metabolism. I wonder if inflammation has an effect on the dopamingergic neurons you discuss… if I remember correctly, inflammation induces leptin AND insulin resistance (via the same pathway) in some neurons as well, and could contribute to the leptin resistance induced (classically) by high circulating levels of leptin.
I was totally unaware of the dopamine tie-in here, thanks for the article!
Right on!
Question–how does one figure out if one is deficient in dopamine? Second question: what is the importance of spacing meals out five hours apart? Forgive my ignorance. I am UNDERweight, and try to eat every couple of hours. Is this bad in overall health and metabolic regulation, etc.?
According to the article it’s possible to determine the deficiency by means of a questionnaire. I’m very curious as to how this works.
Here is a good write-up on the subject, http://www.primalbody-primalmind.com/the-whacky-wild-and-misleading-world-of-neurotransmitter-testing/.
Leptin does increase SOCS3 and therefore makes the leptin receptor slightly less sensitive. Although it wouldn’t make sense if having higher leptin levels induced so much leptin resistance that there was actually less leptin signalling compared to normal leptin levels. This would then cause the whole system to not work.
Numerically, if normal leptin levels and signalling is 1 having 2x normal leptin levels may produce 1.75x leptin signalling, rather than <1
Hey Kevin
Thanks for a nice concise, but educational post on leptin and dopamine. It’s a really interesting topic, but what’s your personal view on re-feeds or diet breaks to reset leptin levels. Some people think a once a week re-feed is fine, others reckon eating at maintenance for a week every 4-5 weeks of calorie restriction (obviously if you are trying to shed body fat)
Also, what sort of body fat % do you see leptin down-regulation as becoming an issue?
Tinker with it and see. I have seen “skinny” people have problems with leptin sensitivity. Checkout the leptin and thyroid connection. I personally do not think it is as simple as a re-feed every so often. There are so many variables that come into play for balanced health. Lepin even plays a role in our stress response! The more we do to promote appropriate health the better.
Lots of stuff here I didn’t know about. Can you just clear up if Leptin affects appetite. If you are there any natural products you know of that may reduce the urge to each all the time?
It controls appetite!
I just checked out Kevin’s site and it is also full of good dieting information. This post is very educational, some of it I didn’t quite understand, even though I read it twice.
I covered leptin on my website and podcast many times. Artificial light and circadian rhythms are more important than anyone realizes. Not enough people are talking about it!
Do you suggest taking it as a supplement?