Insulin Resistance and the Leptin Connection

This article, originally written in Aug 2007 and updated 4/1/21, has been moved from my old iWeb site; it is my intent to move all my remaining insulin resistance articles; see Diet and Health Menuunder “Insulin” for list of these articles about Insulin Resistance.

Briefly, Insulin Resistance (IR) is a malfunctioning of insulin receptors on cell walls, and is the precursor to Type-2 Diabetes. Leptin is an important hormone that plays a role in reversing IR.

Obesity and Type-2 Diabetes

Although some doctors are beginning to come around to the effects of “insulin resistance” to human health, most mainstream medicine believes that obesity leads to (causes) type-2 diabetes.  The truth is that obesity and type-2 diabetes are related by a common precursor: a problem with the complex signaling system that controls sugar and fat metabolism at the cellular level. This system involves several hormones including insulin, leptin, adinopectin and cortisol.

The first of the hormones involved in this signaling system was insulin.  Obese people have high circulating levels of insulin, because their cells have become insensitive to its presence. This is called insulin resistance.  One of insulin’s actions is to bind to specialized receptors on the surface of the muscle cell membranes.  When this binding happens, a chain of events is triggered which causes glucose to be taken up by the cells, where it can either be burned as fuel for energy, or converted to glycogen (animal starch) for short term storage.

When muscle cells stop responding to insulin, sugar builds up in the blood.  Insulin then binds to specialized receptors on hepatic (liver) cells, signaling these cells to convert the excess sugar to fat.  This fat is then stored in the adipose tissue, predominately around the abdomen, leading eventually to obesity.

Meanwhile, more and more insulin is provided by the pancreas as the deprived muscle cells continue to need sugar.  Eventually the pancreas wears out and no longer produces enough insulin, and sugar builds up in the blood.  This condition is known as diabetes.

Thus, both obesity (increase in fat stored in adipose tissue) and diabetes can result from a resistance to the signaling action of insulin.

Insulin and Leptin

In prehistoric times, ancient man was hard pressed to provide balanced nutrition on a daily basis.  He often went through periods of famine and starvation.  The human body learned to adapt by creating a sophisticated system to detect when starvation was approaching and then to store all available food as fat, until a time of plenty could return.

Our modern bodies have inherited this system from our ancestors, except that we seldom encounter periods of true famine.  But when we go on a calorie-restriction diet, this ancient system thinks we are going into a period of famine.  It slows down our metabolic rate, and converts most nutrients into stored fat. 

The primary players in this system are the hormones insulin, leptin, and adiponectin. Leptin and adiponectin are made in the adipose (fat) cells; insulin is made in the beta cells of the pancreas. (For more on the many functions of insulin, refer to my article “Insulin: Master Regulator.” 

While each human is a whole being, it is also made of trillions of independent cells that must communicate with each other, and with the central nervous system in order for the whole to function.  That communication takes place largely by hormones. Insulin and leptin work together to regulate metabolism, the rate at which the body turns food into energy (life), to make the body hum. (3) 

  • Insulin works mainly at the cell level, directing them to burn or to store nutrients, and whether to utilize energy for cellular reproduction, or maintenance and repair. (3) 
  • Leptin works at the whole-body level for weight regulation.  It measures how much energy (fat) is stored; and determines if more is needed, or if some should be burned off.  It also determines whether the time is right (nutritionally speaking) for reproduction (to produce children). (3)  Leptin also signals satiety–sense of fullness–as a signal to stop taking in food; and signals hunger when fuel storage drops below a ‘set point.’ (4) 

Keeping these two hormones at optimum levels is critical to avoiding both obesity and diabetes. A very important part of optimizing hormonal levels is when you eat what you eat (from Dr. Loscalzo (15)).  

There should be at least a 12-hour break (or ‘fast’) between dinner and breakfast; then your breakfast is truly a ‘breaking of the fast.” A 16-hour break between dinner and breakfast is even more important – this is called “intermittent fasting.” Check out Mercola’s articles on this topic; see references (16, 17)].

The guidelines for intermittent fasting are:

  • Allow 3 or more hours between each meal,
  • 3 hours between dinner and bed, and
  • 16 hours between bed and next-day’s breakfast.
  • At breakfast, avoid high-carb foods (sugar, breads, cereal, porridge, etc). Instead, eat protein (e.g., eggs, green smoothie, protein powder, etc) balanced with fat (e.g., fatty bacon, butter, cream, full-fat cottage cheese or yogurt, etc.) and whole fresh fruit (not juiced).

For example:

  • Start breakfast at 9 AM;
  • Start lunch at 12:30 PM (at least 3 hours after  breakfast);
  • Start dinner at 4 PM (at least 3 hours after lunch);
  • Go to bed at 9 PM (at least 3 hours after dinner);
  • Get up at 6 AM (for 8 – 9 hours of sleep);
  • Start next breakfast at 9 AM (at least 16 hours after dinner).
  • Stop eating 3 or more hours before bed, and avoid eating for at least 13 hours after going to bed (a minimum of 16 hours after your last meal).

Following the four recommended guidelines will help return your body to a normal leptin cycle (leptin governs when you are hungry; see also my Ketogenic Diet article)

Body functions influenced/regulated by leptin

Dr. Ron Rosedale says that leptin influences, and may control the functions of the hypothalamus (an endocrine organ at the base of the brain).  These functions include: (1) 

  • Reproduction
  • Thyroid function
  • Adrenal function
  • Sympathetic nervous system.
  • Through influencing  the function of these systems, leptin regulates the following autonomic functions: 2
  • body temperature
  • heart rate
  • hunger
  • stress response
  • fat burning vs storage
  • reproductive behavior
  • bone growth
  • blood sugar levels

Just as with insulin receptors that become insensitive to insulin, leptin receptors may also become defective and insensitive to leptin, which can lead to uncontrolled weight gain. (5)  When leptin levels of obese people are measured, they may be too high, rather than too low, indicating leptin resistance.

Leptin may also play a role in whether one has a ‘sweet tooth.’  Researchers in 2000 injected mice with leptin and then observed their response to different tastes (sweet, salty, sour, and bitter).  The mice showed decreased interest in sweets, but their reaction to other tastes was unaffected.  In the same research, another group of mice was bred to be diabetic.  These mice retained their interest in sweets, even after injection with leptin.

Body fat is made from excess sugars circulating in the blood, then stored in the adipose tissue. If leptin determines that more body fat is needed (either in reality, or because leptin receptors are blocked resulting in leptin resistance), leptin creates a craving for carbs – the sweet tooth. When leptin determines more body fat is not needed, the sweet tooth goes away.

Just as sensitivity to insulin is increased with exercise, so also is sensitivity to leptin; one more reason why physical exercise is critical to weight management. (6)  In fact, there is evidence that leptin resistance is a precursor to insulin resistance.


Adiponectin is another hormone involved in regulation of sugar and fat metabolism.  It increases insulin sensitivity of cells, so that they respond better to the signaling of insulin, to uptake and metabolize blood sugar.  A curiosity is that as one becomes more obese, the less the fat cells produce adiponectin; while there are theories about this phenomenom, none have been proven. (8) 

This inverse relationship between obesity and adiponectin levels is especially troubling because obesity is closely tied to insulin sensitivity.  As insulin sensitivity decreases, the tendency to gain weight (especially abdominal fat) increases.  This increase in abdominal fat further lowers insulin sensitivity, and a cyclic situation develops.

No one really knows which comes first; decreased insulin sensitivity or tendency to gain weight in the abdominal region.  Allopathic medicine is firmly in the camp that believes obesity and lack of exercise/overeating causes insulin resistance and leads to type-2 diabetes.  However, there is no proof of this.  Many researchers believe that something else, perhaps something in the modern diet of synthetic foods, causes the initial decrease in insulin sensitivity, thus stimulating weight gain, which then in turn further lowers insulin sensitivity.

Another theory is that adrenal fatigue, which means cortisol levels are high, reduces insulin sensitivity. 

One study suggests that “adiponectin concentrations are more closely related to differences in insulin-mediated disposal than [to] obesity.” (9)  This means that while levels of adiponectin decrease as obesity (as measured by BMI) increases, the primary effect of adiponectin is to decrease insulin sensitivity, rather than to increase fat storage.

Myo-inositol and Insulin Resistance

This section added 4/1/21

Myo-inositol is a B-vitamin that was declared non-essential; however, as we age, we may not make enough of it. It’s main role is stabilize cell membranes so the cell can communicate with other cells; for example, if insulin receptors (on the cell membrane) have stopped working or disappeared altogether, insulin cannot help sugar enter the affected cell. So the cell(s) call for more sugar but still cannot enter the cell(s) so both sugar and insulin build up on the blood, leading the liver to convert the sugar to storage fat, which are transported to the adipose tissue in the belly region.

Once the receptors are restored (by the moo-inositol), the cells can receive the sugar, to slow or stop conversion of the sugar to body fat. I can testify to that by personal experience!

See my article  Choline, Inositol, and Insulin Resistance for more.

Fat Hormones and Weight Control

In laboratory experiments on animals, administration of leptin causes weight loss by suppressing appetite and increasing metabolism.  Similar results have not been obtained with human subjects, but research continues.

When injected into lab animals, adiponectin also causes weight loss, but does not appear to affect appetite; rather, weight loss is a result of increased metabolism alone.  

Both leptin and adiponectin are made in adipose (fat) tissue, and affect glucose (sugar) and lipid (fat) metabolism by exerting their influence on the brain. (7) 

Researchers, at this point, are not indicating that the fat hormones such as leptin and adiponectin will be administered as drugs for long term weight loss.  Indeed, they have not been able to produce the same weight loss by injecting these hormones into humans, as they have effected with lab animals.  But a better understanding of the weight control mechanisms may lead to new drugs for safe weight control.

In the meantime, Mary G. Enig believes that including coconut oil in the diet can be used to stimulate long term weight loss.  The medium chain fatty acids in tropical oils like coconut, have the ability to increase metabolism and to stimulate satiety, for appetite suppression.  The exact mechanism by which these effects happens is not yet known.  Another weight-benefit of coconut and other tropical oils is that the medium chain fatty acids are more readily metabolized (burned for fuel) than other, longer chain fats, because they do not need to be processed in the liver first.  This makes them an excellent source of quick energy, ensuring that they will not be converted into body fat for storage.  (9)

A Disease of Nutrition

Drs Mercola and Rosedale believe that diabetes (and insulin resistance) is a disease of nutrition, and I agree, but I don’t necessarily agree with the dietary changes they recommend (back in 2007 when I wrote this article).  Mercola suggests a diet devoid of starchy carbs (grains, breads, sweets), but high in vegetables (and fruits to a lesser extent), and balanced for protein and what they call “good” fats; (i.e., the ketogenic diet).“Science is telling us that we must eat a diet that maximizes the accuracy of insulin and leptin signaling allowing cells, you, to better listen to their life-giving messages. (The need for those hormones to have to “yell” to be heard is reduced and the levels of insulin and leptin are therefore lowered.)” (1) 

However, when I decided to start a keto plan, everything started to change. I did not lose weight, but my cravings for sugar and starchy foods went away. A few years later, I added myo-inositol to my diet (at the suggestion of my naturopath), I lost 30 pounds and felt like a “new woman.” I can attest to it’s benefits!

I’ve not purchased their books on diet (The Rosedale Diet; Mercola’s Total Health Program), so I’m not familiar with the details, but I do think a total ban on whole grains is a little extreme.  

Sally Fallon, in her book Nourishing Traditions, advises using whole grains that have first been sprouted or soaked in whey, which makes the nutrients in the grain more bioavailable, thus increasing their nutritional value. This is an ancient technique which has historical merit; traditional peoples are free of the modern diseases of nutrition by which we are so troubled.  Sprouted or soaked whole grains provide fiber which slows down the absorption of sugar, to avoid blood-sugar spikes.  They also provide enzymes, vitamins and minerals to assist in proper assimilation of the nutrients provided by the grain, as well as those provided by other foods ingested at the same time. (10) 

Mary Enig, coauthor of Eat Fat Lose Fat (with Sally Fallon) cites a need for increasing the amount of certain fats in the diet, specifically medium-chain fatty acids in fats such as coconut and palm oils, and Omega-3 fats in cod liver oil, butter (from pasture-fed cows), eggs (from pasture-fed hens), and raw dairy.  Coconut oil consumed before a meal provides many benefits, not the least of which is to incite the secretion of leptin, signaling satiety, so that one doesn’t eat too much.  Cod liver oil provides, in addition to the Omega-3 fats, vitamins A and D.  All fats slow down the rate of absorption of sugars, to avoid blood-sugar spikes; hence the importance of buttering your bread (or dipping in olive oil); of dressing your veggies with an oily salad dressing or melted butter; and of dipping fruits in creme fraiche or yogurt. (11)

References and Sources:

  7. this article is no longer readable
  10. Book: Nourishing Traditions by Sally Fallon with Mary G. Enig, Ph.D.
  11. Book: Eat Fat Lose Fat by Mary G. Enig, Ph.D. with Sally Fallon
  13. and 
  15. Dr Ritamarie Loscalzo’s book The 12-Hour Break that Burns Away Belly Fat and Accelerates Healing (see pdf, not secure:   and video: )

About Cat

See my 'About' page
This entry was posted in Health, Uncategorized and tagged , , , . Bookmark the permalink.