The Hormones of Fat: Leptin and Insulin

October 23, 2012 in Categories: , by

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Hormones tell your body whether to burn fat and lose weight or to store fat and gain weight or to find balance and weight maintenance in between.  When it comes to your body “deciding” what state to be in, there are two key hormones that regulate food intake and energy balance:  the adipocyte hormone leptin and the pancreatic hormone insulin.  While there are many other hormone players with complex interactions between them, understanding these two hormones (which you could think of as the hormones of fat) will give you important insight into how the diet and lifestyle choices you make can help you achieve and maintain a healthy weight.

The hormone insulin, which is released by the pancreas in response to increased blood sugar, facilitates the transport of glucose into the cells of your body and signals to the liver to convert glucose into glycogen for storage.  When glycogen stores are maxed out, increased insulin levels stimulate conversion of glucose into triglycerides (fat) for long-term storage in adipocytes (fat cells) 1.  But beyond this important action for the metabolism of fuels, insulin has an additional role as an adiposity signal to the brain, i.e., it tells the brain whether or not you should eat and informs the brain about the energy status of your body.

The major stimulant of insulin secretion is an increase of blood glucose levels, as detected by the pancreas (blood glucose levels go up when you eat carbohydrates).  Circulating insulin enters the brain (proportionally to the amount that is circulating in the blood) where it binds to receptors in the hypothalamus region of the brain.  Although the exact details are unknown, it is understood that through this interaction with the central nervous system, insulin stimulates a decrease in food intake 2,3.  This makes some sense.  You eat, your blood sugar level rises, your body releases insulin to store all that glucose, and that increase in insulin tells your brain that you’ve got enough energy, thank you very much.  Importantly, the degree of glucose-stimulated insulin secretion by the pancreas is a direct function of body fat 4,5.  The more body fat, the more insulin is secreted both at a basal level and in response to feeding.  There is also a maximum amount of insulin that can actually cross the blood-brain barrier to stimulate satiety.  As the blood concentration of insulin increases beyond this level, no further signaling to the brain can occur.  Insulin resistance occurs when more insulin is required to maintain a normal level of blood glucose, and potentially when there is a decrease in insulin receptors in the brain, meaning that those high levels of circulating insulin don’t decrease appetite the way they are supposed to.

Fat storage cells, called adipocytes, produce the hormone leptin, which acts as a negative feedback control for adiposity (fatness).  Leptin is secreted by adipocytes (fat cells) in direct proportion to the amount of stored body fat, in particular, the amount of subcutaneous fat.  Similar to insulin, circulating leptin enters the brain where it binds to receptors (there are receptors for leptin in the hypothalamus but also several other areas of the brain).  Again, the exact details are unknown, but it is understood that leptin’s interaction with the brain stimulates a reduction in food intake and increasing energy expenditure 6.  This also makes some sense.  You have a good amount of fat stores, leptin is released and tells your brain that you have enough energy so you don’t need to eat anymore and hey, let’s get moving!  And analogous to insulin resistance, the body can also become leptin resistant, although this can happen from both obesity and overconsumption of energy 7 and by fasting or consuming too few calories and losing weight 8!  Uh, yeah.  Leptin is tricky.

It was initially believed that leptin’s dominant role was to tell the brain to stop eating.  However, recent studies have shown that it mediates the adaptation to fasting 8Fasting or consuming too few calories on a regular basis can lower sensitivity to leptin, which leads to increased hunger, cravings and lack of energy.  This has a very important implication in weight maintenance after weight loss since reduced leptin sensitivity is likely responsible for lowered metabolism and increased hunger, a combination that tends to lead to weight gain (why it’s so hard to keep weight off after going on a diet).  There is also a link between leptin and cortisol release, potentially explaining the cortisol spike that many people experience in response to intermittent fasting.  The many roles of leptin in the human body are still being studied.  It has also been implicated in the regulation of the reproductive, thyroid, growth hormone, and adrenal axes, independent of its role in energy balance.

To date, only the hormones leptin and insulin are known to act as adiposity signals 9.  The amount of leptin and insulin in the blood correlates with adiposity.  There are receptors in the brain for both insulin and leptin in areas of the brain known to be important in the control of food intake and energy balance.  Studies which have injected insulin or leptin show that this causes a reduction in food intake, whereas injection of antibodies to block insulin and leptin causes an increase in food intake.  Importantly, recent studies have demonstrated that insulin and leptin have additive effects when administered simultaneously 10.

What are the implications of this information for those who want to lose weight?  I think there are two major take home points here:

  1. Controlling insulin by avoiding high blood sugar is important for regulating hunger.
  2. Slow and steady wins the race in terms of weight loss and leptin sensitivity. 

I will be continuing to discuss many different hormones and the roles they play in health and weight loss over the next few months.  Leptin and insulin will feature prominently in these posts.

1. Click here for more information on insulin and its role in metabolism.

2. Begg DP and Woods SC. “The central insulin system and energy balance.” Handb Exp Pharmacol. 2012;(209):111-29.

3. Woods SC et al “Signals that regulate food intake and energy homeostasis”. Science. 1998 May 29;280(5368):1378-83.

4. Polonsky K S et al “Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects.” J Clin Invest. 1988 February; 81(2): 442–448.

5. Polonsky KS et al “Quantitative study of insulin secretion and clearance in normal and obese subjects.” J Clin Invest. 1988 Feb;81(2):435-41.

6. Ahima RS et al. “Leptin regulation of neuroendocrine systems.” Front Neuroendocrinol. 2000 Jul;21(3):263-307.

7. Enriori PJ et al “Leptin Resistance and Obesity” Obesity (2006) 14, 254S–258S; doi: 10.1038/oby.2006.319

8. Ahima RS.  “Revisiting leptin’s role in obesity and weight loss.” J Clin Invest. 2008 Jul;118(7):2380-3.

9. Benoit, SC. “Insulin and Leptin as Adiposity Signals” Recent Progress in Hormone Research 59:267-285 (2004) (link to the paper here)

10. Air EL et al “Insulin and leptin combine additively to reduce food intake and body weight in rats.” Endocrinology. 2002 Jun;143(6):2449-52. (link to the paper here)

Comments

How is it that your posts are always so relevant to me personally? Have you been reading my journal? This is exactly the information I was searching for on the web yesterday. Thank you so much for being so awesome and clairvoyant! I appreciate your detailed footnotes too.

I suffer from LGS, Thyroid issues, and Candida and was wondering how my cortisol levels and insulin levels are affected by my mentioned conditions. I feel that as soon as I came down with these health issues, i began packing on fat in my abdominal area and cellulite has appeared as well. What are the best ways to combat this?

It does sound like cortisol issues, although which one is the chicken and which one is the egg is hard to tell. Sleep is your best friend. Gentle exercise like walking. Sun exposure and vitamin D3 supplementation. Carbohydrate intake on the low side, but not too low (think 75-100g per day, which roughly equates to lots of non starchy veggies and 1-2 servings of either fruit or a starchy vegetable). Something like mindful meditation, yoga, tai chi, making time for your favorite hobby, whatever you can do to relax. Also doing what you can to reduce inflammation through diet (strict paleo diet, with the thyroid issues, you might want to have a look at the autoimmune protocol), including gut healing foods like bone broth, coconut oil, grass-fed meat and wild-caught fish, organ meat, and a probiotic supplement. I hope this helps!

THANK YOU! You do have a great writing style that makes it easier for us non-scientists to understand complicated topics.
I suffered from adrenal insufficiency, with virtually no cortisol production at all, for several years. Will ever write about this condition?

Eventually. The less I know about a topic, the longer it takes me to write about it, but I do have some posts mapped out about cortisol which should be posted in the not too distant future. Do you know why you have adrenal insufficiency? Is it Addison’s?

LOVE this information…explains my situation perfectly…I have practiced intermittent fasting for the past 15 months…and I have absolutely no desire to leave the house.but only in the a.m:!!!..my energy is so depleted and I feel kind of weak, foggy and find it difficult to get anything done or “focus”…until the “allotted” period has passed (no caloric consumption between 9pm and around 3 or 4 pm the next day…

I was a bit scared whilst driving yesterday..because my hands became ice cold and clammy…my heart “raced” or beat too fast for a period of 3-4 hours, off and on in the afternoon…and I felt as if I was going to faint or have a heart attack…driving and during a movie…I was with my daughter!!!…So afraid I wouldn’t be able to pull over in time to “sit it out”….or that I would lose consciousness during “Les Misèrables”…with her right next to me…My throat was so dry..and almost seemed to close up.or constrict…Does this have anything to do with the brain/gut chemistry you wrote about so eloquently?…

Frankly…I am frightened…I hope this never happens again…but I wonder if keeping “too large of a fasting window” and the length of time I “honored” …what was an admittedly self-imposed “Paleo Rule”…wreaked havoc upon my health…My metabolism is non-existent..or irretrievably broken. I am nearing 53 years of age…am ten years into a battle with food issues..(anorexia nervosa and generalized terror around food).

While I desperately WANT to be kinder to my body and honor it’s health….and protect that of my daughter’s!!…I find that I can live on VERY few calories to survive…and anytime I up them…the weight LOADS on….

If you have an idea to keep these sort of attacks at bay ..was it hypoglycemia?….please let me know….

Thank you for the important information regarding leptin and insulin….

This sounds like fasting is absolutely not working for you. Fasting can cause cortisol spikes, leptin resistance and insulin resistance, which is why you gain weight whenever you stop. The only way to get through this is to stop, deal with the weight gain, and let your body adjust and regulate hormones better. I would suggest moving to 2-3 BIG meals per day (you can fill up on non starchy veggies if you’re worried about too many calories, the fiber is actually great for hunger hormone regulation), with a much larger feeding window. Make sure you are getting as much sleep as you possibly can (which will help limit how much weight you gain and help your body adjust more quickly), get outside for 15 minutes every day (which will help improve the quality of your sleep), get some light activity like walking (strenuous activity is not going to help regulate cortisol and hunger hormones while you adjust). There is some pretty convincing research showing that fasting is not beneficial in women and I know from my personal experiments with it, that I am absolutely healthier if I eat a big breakfast (if I ever skip a meal, it’s lunch, but that’s only when I’m not hungry).

The hormones still have the same roles in your body. The difference is that your pancreas isn’t able to produce insulin (or enough insulin) as would happen in someone without T1D.

Since insulin is a fat-storage hormone, is it possible that the insulin I am injecting (60 units of Lantus, 30-40 units Humulin R – that’s the total units I inject in divided doses daily) is preventing me from losing weight? I have been eating low carb for many years, totally wheat-free for almost two years with no cheats. I am on many meds, but I wonder if it is the insulin which is keeping me from losing weight?

I feel stuck between a rock and a hard place. There are dangers with both elevated blood glucose and high levels of insulin.

TY!

Hello, this post was super timely for me, as well. I’ve been paleo for several years and just recently, beginning of March, implemented the AI and FODMAPs protocols while significantly reducing carb/sugar intake. My carb/sugar intake was low relative to the average American, but still too high form me. I realized that I kept switching from one sugar to another; honey then maple syrup, then coconut sugar, then ready made paleo treats and the more I ate the more I wanted.
Over the course of this month, since implementing AI, strict lower car intake and FODMAP protocols, I have noticed an overall reduction in hunger. I need to eat fewer times per day, which is great for many reasons, not the least of which is the time and energy needed for prep and packing.
I also wanted to mention something about sugar cravings for everyone. Several years ago I had uncontrollable, mind bending sugar cravings that did not go away despite major nutritional changes. Eventually, I found out I had two serious intestinal infections, one bacteria and one super nasty parasite. These two organisms were stealing my nutrients causing me to need to eat 7 or 8 times a day, drink more than 120 ounces of water a day and crave sugar to the point that it was continually on my mind. The cravings, foggy brain, and extreme fatigue went away only after eliminating these infections from my body. It took a few years to recover from them.

My husband and I lost a lot of weight after going Paleo, but have recently started gaining it back. Two potential culprits come to mind … lack of sleep due to a small child and increased intake of energy boosting products. The comment in the article about “overconsumption of energy” made me pause. What exactly is meant by that? Could drinking energy products be what’s meant here? I could use some additional clarification on this, as well as ways you can reduce leptin resistance, or reset your body.

Donna was having a panic attack and anorexic people shouldn’t do fasting at all. I suspect Donna is already underweight. Hence all her problems.

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