the truth about leptin resistance

Leptin is one of the reasons I love my job.  I know that sounds a little insane but it’s true.  One of the big reasons I love being a nutritionist is having the unique opportunity to unravel the mystery of the health issues of my clients.  Sometimes it takes some digging but it is so satisfying when we identify what is really going on and even more so when you can help someone repair what’s ‘broken’.  

So again, leptin is one of the reasons I love my job.  Don’t get me wrong, thyroxine (both T4 and T3), cortisol and any and all of the sex hormones get me pretty psyched too but leptin has a special place.  Yes, I know, I sound nuts but I just love biochemistry.

So why is leptin (and, consequently, leptin resistance) so gripping?  

In a word, leptin has a lot of power.  We discussed the role of leptin in great detail in yesterday’s post The Lowdown on Leptin Pt. 1. In a way, the body is like a mafia.  The brain is the Godfather and leptin is the consiglieri.  Leptin knows everything about the body and it knows where the bodies are buried.  Leptin knows everything about how much energy the body has and leptin decides when it needs more and even decides how to spend the energy it has.  It all depends on leptin levels. 

Think of leptin as an orchestra.  When the conductor tells the orchestra to play ‘pianissimo’ it’s telling leptin levels to drop to signal to the brain that it is time to eat and to lower the metabolism to conserve energy stores. (It talks to the thyroid to lower metabolism.)  When leptin levels rise, the orchestra is given the instruction to play ‘fortissimo’ and the brain tells the body to stop eating and raises metabolism because the body has enough energy to have all the organs functioning as they should.  

This is all fine and wonderful until something goes wrong.  The irony is that a little leptin goes a long way.  Thinner people have less of it and the more overweight a person gets the more leptin is produced.  Think about it this way.  Fat cells of a thin person are very small and produce a little leptin that shouts at the body “FEED me Seymour!!” when the body needs more fuel to function.  As more weight piles on, fat cells get bigger and produce more leptin.  This is a little like adding many conductors and combining three or four orchestras all playing different symphonies.

I know what you are thinking.  “But you said when leptin levels rise it signals us to stop eating and raises metabolism!”  That’s true when the rises accompany a fall in a sensible cycle.  Think of leptin as the little boy who cried wolf though.  The little boy cried wolf (lowering the leptin levels), the townspeople came (raising leptin levels.)  He cried wolf again, the townspeople came.  Leptin levels fell and rose.  He did it a few more times and the townspeople just started coming more slowly until they stopped listening altogether.   Essentially, the brain just stops listening to all the circulating leptin and becomes leptin resistant.  That is when the brain assumes it no longer can tell when the body needs or doesn’t need fuel and tells it to keep filling ‘in case’ there is a need.  And because leptin is no longer being heard by the brain, the brain has to tell the less vital organs and functions “sorry buddy, we don’t have enough fuel to keep us alive so you have to just stop functioning”.  The body is in a constant ‘starvation’ mode where the metabolism is significantly lowered and the appetite is increased even after a full meal is eaten.

It should be noted that you can still have leptin resistance if you are very thin.  It does not mean you have an abundance of leptin but your brain can still not listen to its signals so you will still be in a starvation mode.  Think about cases of anorexia nervosa as examples.  

What are the signs and symptoms of leptin resistance?

  • Overweight or obese
  • Fatigue after meals
  • “Love handles”
  • High blood pressure
  • Crave “comfort foods” like potatoes, bread, cakes and cookies
  • Easily anxious, angered or stressed out
  • Hungry all the time or at odd hours, like at night
  • Osteopenia or Osteoporosis
  • Difficulty losing weight or keeping it off
  • Sugar cravings
  • An addiction or reliance on stimulants such as coffee or other caffeinated beverages or amphetamines
  • Increase in triglycerides
  • Urge to snack after meals
  • Trouble falling or staying asleep
  • Inability to change body shape no matter how much one exercises

I know many of you are reading this list and thinking that these symptoms could be related to thyroid, adrenals, and hormonal imbalance and you would be absolutely correct.  But here’s the rub.  Leptin is always involved in these endocrine dysfunctions so for those of you who are thinking you are hypothyroid or have adrenal insufficiency or even PCOS you might want to read on.

Leptin is part of a whole hormonal cascade.  We talk a lot about hormonal cascades when we talk about HPA axis (c0ming soon) and OAT axis imbalances.  When something is off it throws the whole system off kilter.  Up until now I have resisted talking about leptin because there isn’t as quick of a fix as, say, supporting thyroid or helping calm adrenals.  Also, since I tend to treat ‘downstream to upstream’ leptin is always at the top of the stream.  Still, since I have been encountering some pretty complex cases in my private practice leptin and the treatment of its resistance is becoming more and more necessary.

Let me confuse you even further by saying for all those with hormonal issues, thyroid issues, and adrenal issues,  and insulin resistance you, more than likely (read:: you DO!!) have leptin resistance issues.  

We know already that a slow or even broken metabolism causes multiple systems to slow down or even fail.  We also know that leptin dictates to the body how much energy is available and where metabolism should head, up or down.  Our bodies really haven’t adapted much from the spring/summer feasts and winter famines of the time before supermarkets and our bodies really weren’t meant to be able to digest a lot of the industrialized food like substances that are mostly carbs so this system gets out of whack really quickly.

We already talked about leptin being greatly responsible for bone physiology as bone requires a lot of energy to keep up with the stresses of day to day life.  (Especially all the overtraining, snowboarding, water skiing and other crazy things we do for thrills these days.)  In fact, leptin plays such a role in bone synthesis and formation that chronic leptin resistance is an indicator of the future development of osteoporosis.  For all of you who have been diagnosed with osteopenia (a reversible indicator of future osteoporosis) treating leptin resistance should always be part of any treatment plan.

Leptin resistance is also, generally, a factor in fertility issues and, in my practice, it is the one time I actively work on leptin sensitivity without question.  Creating a baby takes an enormous amount of energy from the body.  When metabolism is slowed down fertility issues almost always are present.  In cases of PCOS and unexplained infertility, (where there is always insulin resistance as well) treating leptin resistance in addition to supporting insulin function, thyroid function and the adrenals and being very sure detox pathways are clear and functioning properly almost always leads to fertility being restored and pregnancies occurring naturally.  

In obesity, higher than normal levels of white blood cells are the norm as leptin is partly responsible for immune modulation.  Remember, the fat cells release inflammatory compounds called cytokines and visceral fat (deep abdominal fat that is the most resistant to weight loss as it surrounds the organs) is the most inflammatory of all.  Those with this kind of fat have a greater tendency towards high blood pressure and high blood pressure triggers its own cascade of physiological havoc.  This sinister fat is the type of fat found in NAFLD (non alcoholic fatty liver disease) and causes a host of other issues including metabolic syndrome and type 2 diabetes.

Leptin resistance, if not treated, is a runaway train towards insulin resistance and Type 2 diabetes.  Elevated leptin destroys a protein in beta cells (the cells that manufacture insulin) called amylin.  When leptin has completely destroyed the function of amylin the pancreas stops making insulin altogether.  Now, as with premenopause making a lot of estrogen right before estrogen levels decline sharply in menopause, before the pancreas is completely spent it steps up insulin churning.  As with leptin, when there is a chronic insulin elevation the receptors simply stop listening.  This is called insulin resistance.

Leptin resistance is a precursor to insulin resistance (often by up to 5-7 years!).  Because these dysfunctions cause a great deal of stress on the body and insulin dances with cortisol as cortisol inhibits insulin in a bid to help the body use glucose as fuel for the ‘fight or flight’ scenario it perceives as a necessity. Elevated cortisol leads to greater visceral fat storage as it is able to mobilize triglycerides from adipose tissue and store them in visceral fat cells for quick mobilization.   There are all kinds of reasons why this is is a bad thing but I will break it down to you easily.  Elevated leptin leads to the body not listening to leptin any longer which means eventually it will stop listening to insulin and finally it will stop listening to cortisol.  Those of you with adrenal resistance (or insufficiency or fatigue) will be thrilled to know that treating your adrenal resistance must include treating your leptin resistance and even looking at how your body is processing insulin as there is generally at least some kind of insulin handling disorder.  (It’s why those with adrenal fatigue often have hypoglycemia symptoms.)

I know this post is a book already but I have one last (and possibly my favorite part of this whole chaotic sounding system) dot to connect for you.  Those of you with hypothyroid symptoms will be thrilled to know that leptin is probably causing those symptoms and restoring leptin sensitivity will generally restore thyroid function.  It’s quite complicated how it all happens but essentially when the body is leptin resistant it creates an antagonist to thyroid hormone called reverse T3.  Those of you who have worked with me know that I will almost always ask for an RT3 test in a full thyroid panel.  This test is an indicator for leptin sensitivity.  

You all know by now reading about thyroid function that there are many ways your thyroid can ‘break’.  For women, it is generally the fact that T4 (inactive thyroid) not converting to T3 (active thyroid) which is converted in the liver and, since many women with estrogen dominance/progesterone deficiency have a defect in their detoxification process, this is usually a simple thyroid problem that present hypothyroid symptoms.  The body also could have an inflamed or stressed thyroid because there aren’t enough nutrients to support the creation of T4.  Both of these scenarios can cause a host of other issues including sex hormone balance issues (everything rolls downstream, remember?).  

Leptin resistance, by virtue of putting the body in chronic starvation mode, turns OFF the thyroid creating a slew of hypothyroid symptoms in addition to further down regulating the metabolism.

Confused?  Don’t worry, while it sounds complicated, there are professionals that can help unravel your host of symptoms and put you on a plan that makes sense to get your body listening to your hormones again and supercharge your metabolism! 

Tomorrow we will be discussing a few lifestyle changes you can make to increase your leptin sensitivity.  

How many of these symptoms do you have? Is your body listening to the signals it needs to hear to keep your metabolism humming?


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