Leptin not working?

May 24, 2011 4 Comments by Scott Isaacs MD


Leptin is a hormone made by fat cells that was first discovered in 1994 by Jeffery Friedman.  It is the original “hungry hormone.”  Like all hormones, leptin is a chemical messenger.  When it comes to leptin, the message leptin sends is “I’m full.”   Leptin is produced by fat cells, travels through the blood stream and then works in appetite centers of the brain, signaling feelings of fullness.  When leptin levels are low, you feel hungry and are motivated to seek out food.

People with leptin deficiency are hungry all the time and very overweight.  They can take leptin injections and lose lots of weight without diet or exercise.  The problem is that leptin deficiency is extremely rare.  In my career, treating thousands of overweight and obese patients, I’ve never seen one case of leptin deficiency (neither have any of my colleagues.)

So if leptin deficiency is so rare, why all the excitement about this hormone?  It turns out that most people who are overweight or obese have dysfunctional leptin.  In fact, their fat cells make huge amounts of leptin.  But, since the leptin isn’t working properly, the massive amount made is still insufficient for suppressing appetite, leaving a person feeling hungry all the time.  In effect, even though leptin levels are high, since it doesn’t work properly, the body thinks leptin is low.  With leptin resistance, the brain isn’t getting the message that it is time to stop eating, time to lose weight.  Leptin resistance results in the brain protecting the body from perceived starvation, even in people who are profoundly overweight.

The following are symptoms of leptin resistance.

  1. Do you feel hungry all the time?
  2. Do you have unexplained weight gain?
  3. Is your weight slowly creeping up over time?
  4. Do you have cravings for comfort foods, fast food or high calorie foods?
  5. Are you not hungry for breakfast or skip breakfast?
  6. Do you overeat at supper?
  7. Do you have excess body fat?
  8. Do you have unusual eating patterns, or does your diet vary significantly from day to day?
  9. Does weight loss stall after losing only 5-10 pounds.
  10. Do you have insulin resistance, metabolic syndrome, prediabetes or diabetes?
  11. Do you have arthritis, asthma, lupus or allergies?
  12. Do you have high blood pressure or elevated cholesterol?
  13. Do you have poor sleep, disrupted sleep or short sleep?

If you answered “yes” 3 or more of these questions, there is a good chance you have leptin resistance.

Leptin resistance means that your brain thinks you are starving when the reality is just the opposite.  Dysfunctional leptin drives appetite and especially cravings for high calorie foods and junk foods.  The brain is doing anything it can to prevent starvation.

Leptin resistance also causes lower metabolism and can lead to a host of other hormone problems like insulin resistance, type 2 diabetes, polycystic ovary syndrome, low testosterone (in men) and thyroid problems.

How do you fix leptin resistance?

In my next blog post, I’ll show you ten ways to make your leptin work better.




  1. Brenda Worsham says:
    Monday, July 8, 2013 at 12:31pm

    I just found this article dated May 24, 2011, Leptin Not Working?.At the end thie author states, “Next week I’ll show you ten ways to make your leptin work better. How can I get the article for the following week?

  2. Scott Isaacs, MD says:
    Monday, July 8, 2013 at 12:44pm

    The article is called “Top Ten Ways to Alleviate Leptin Resistance.” Here is the link.


  3. Kate C says:
    Wednesday, March 19, 2014 at 1:46pm

    I just want to Thank You, I have hypothyroidism and it has given me such a hard time and when I read these two articles I started doing the things I could ( i cant have green leafy veggies due to issues they cause) but I started juicing blueberries and cherries and drinking that 4 times a day taking zink and Omega 3’s and my constant hunger need has gone away, making it easier for me to not only eat better, but fell less tired ect. Thank you for helping people like me, it is a blessing !

  4. L says:
    Saturday, December 6, 2014 at 11:07pm

    I may be the one person who does have leptin deficiency. Ten years ago had an adrenal gland removed because of Cushings. My Dr. Said in his 30 years of work I was the first actual Cushings case he had ever seen. I skyrocketed from about 140 pounds to 200. I also have an autoimmune condition. When I had the Cushings I never felt full. I still have that problem and have never been able to lose the weight, pretty much stays around 190 no matter what I do. Are lepitn injections actually available?

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