Adiposity Hormones

Food intake and energy balance are controlled by the neuronal interactions of a wide variety of gastrointestinal sensory signals from gut peptides to neurotransmitters and things we can call adiposity signals. Only a few though are considered key "controllers" of energy balance. These key controllers reveal themselves when you create an energy deficit. Reduction or elimination of food intake results in a rapid initial decrease in circulating leptin levels and insulin. Leptin levels continue to decrease with continued fat loss.

With a decrease in circulating leptin levels comes a decreased delivery of leptin to the central nervous system (CNS)which alters the balance of several hypothalamic neurotransmitters which brings about an increase in appetite and food consumption.

Conversely leptin and insulin reduce food intake through their interactions with short-term satiation signals such as the intestinally derived gut peptide, cholecystokinin (CCK).

Circulating ghrelin appears to act along with leptin as an adiposity signal in the CNS. Food restriction/elimination increases plasma ghrelin levels which together with the decrease in leptin rapidly stimulates food intake.

It is the trilogy of leptin, ghrelin and cholecystokinin (CCK) that we are most concerned with in the control of food consumption. If you are unable to control the intake of food, insulin levels really won't matter for the reason that you simply will not lose fat.

Like insulin, long-term elevations in leptin, (due to increased adiposity stores) can lead to resistance in leptin signaling and deficits in the ability of these adiposity hormones to neuronally affect body weight regulation. So an overfed state that continues for long periods of time leads to fat accumulation and elevated levels of leptin which brings a decrease in sensitivity to the effects of leptin.

Each macronutrient (fats, carbohydrates and protein) present in the diet can affect these body weight signaling pathways differently. Since macronutrient composition is very important lets look at what happens.

Low Carb Higher Fat/Protein Diet

Carbohydrate-restricted diets with relatively elevated monounsaturated fatty acids and protein, have been found to be effective in reducing body weight, total body adiposity, blood pressure, and waist circumference in overweight people. This type of diet has been found to lead to significant reductions in circulating adiposity signals (leptin and insulin), significantly increased ghrelin concentrations, and significantly increased post meal rise in CCK concentrations (short-term satiation signals) without bringing about an increase in daily food intake.

What happens is that ghrelin increases and leptin decreases and as would be expected subjectively people report feeling less satisfied. However subjective assessments can not be trusted because people lose fat. Yet the rise in ghrelin and lowering of leptin should increase hunger.

The explanation is simply that the satiety signaling through escalating cholecystokinin (CCK)levels is increased day by day. A person eats a meal with higher fats and protein and low carbs and they feel satiated because cholecystokinin (CCK)levels are higher then if they were eating a different macronutrient profile. Over time each meal will result in higher and more prolonged cholecystokinin (CCK)levels which further increases feelings of fullness. This peaks about 2 weeks after staring this type of diet. At that time cholecystokinin (CCK) following a meal remains elevated at least to two (2) hours post-meal. This allows individuals to go without eating for longer periods of time which is very important in bringing about fatloss.

It is chronic exposure of the small intestine to protein and fat that brings about release of CCK from intestinal endocrine I cells. Circulating CCK binds to CCK-1 receptors in the dorsal vagal complex (a region that controls meal size) and satiety ensues.

However increased cholecystokinin (CCK)levels are not sufficient to completely over come hunger induced by elevated Ghrelin and lower Leptin levels. A second explanation is simply that leptin sensitivity in the CNS is increased. The conclusions of these studies is that a carbohydrate-restricted diet together with weight loss normalizes leptin signaling.

It is a narrow rope we walk though because a substantial body of work finds that high fats in the diet can lead to leptin resistance. Lets take a look at what we could say is an opposite type diet and see if we can reconcile this apparent disparity.


Low Fat High Carb/Protein Diet


Fat-restricted diets, produce weight loss by increasing CNS sensitivity to leptin, allowing energy intake, adipose mass, and leptin levels to fall without a compensatory increase in appetite.

These types of studies often find either no or more often some decrease in leptin levels. The failure for leptin fall to bring about increased food intake is attributed to a rise in leptin sensitivity. The conclusion of several studies is simply that dietary fat restriction enhances leptin sensitivity in the CNS and the periphery and that returning people to 35% fat diets rapidly abates the increase in leptin sensitivity.

In addition these diets do not increase Ghrelin levels so Ghrelin will not act to induce hunger. CCK also does not appear to be increased so there is no rise in satiety signally. The sole mechanism to explain the feeling of fullness is an increase in leptin sensitivity.


Reconciling the two macro-nutrient extremes

In my opinion it is the continued presence of both carbohydrates and fats in a diet that results in decreased leptin sensitivity and removal of one in a diet will enhance leptin sensitivity.

Toggling between these two extremes probably has some benefit. The worry is often that circulating fatty acids may bring deposition in organs and muscle and this will lead to insulin resistance in peripheral tissue as well as effect health. It will be important to better match energy utilization with energy input when ingestion of fats is used as an energy substrate. We must also keep an eye on the liberation of fatty acids into circulation.

A diet such as a carbless PWO relies heavily on protein and fats are adjusted to match energy needs. When you break a carbless PWO diet I am conjecturing that 8 hours of carbup will not substantially hinder the build up of cholecystokinin (CCK)levels that we enjoy with just proteins and fats.

If you prolong the Carbless PWO or really any diet w/o carbs for 48 hours + I feel very confident in saying that an 8 hour carb up will not effect the increase in cholecystokinin (CCK)levels and that a quick return to carbless will mean that after several weeks of this toggling eating pattern will result in increased feelings of post-meal satiety and the ability to go w/o a meal for longer periods of time.

This would require that you lift weights every third day. An every other day weight-lifting program would mean less of a percentage of time in the carbless state and I am unsure how that would effect cholecystokinin (CCK)levels. However a true fatloss protocol is primarily focused on muscle preservation and significant fatloss and so an every third day weight-lifting pattern would be exactly what you would want.


How does this fit within a fat loss plan?

The overall goal is to maintain significant periods of time when the body will mobilize the release of fat stores and use them for energy. Energy input, especially of the kind that will result in prolonged periods of storage activity interfere with the overall fatloss goal. Keeping the primary storage hormone insulin quiet is absolutely necessary so that we may spend significant periods of time engaged in lipolysis.

During this period of time we will want to be in an energy deficit. This will not happen if we are unable to control those forces that prompt us to eat. To that end taking steps to increase leptin sensitivity and build up CKK levels serves our purpose.

Using GHRP-6 (which is a ghrelin mimetic) is unwise as it will increase feelings of hunger. Growth hormone as we will discuss is a tool we will use to increase the release of fatty acids from fat cells so we will need to increase its release. We do not want to do this at the expense of violating the satiety we work so hard to build.

GHRP-2 and Ipamorelin are two GHRPs that are capable of increasing the GH we will need without making us hungry.