The hypothalamus is the area of the brain where a cofluence of nerves converge to regulate many activities. A place responsible for interpreting signals and detecting momentary changes in chemistry.

Nerve transmissions depend on the neurotransmitters serotonin, dopamine and norepinephrine.  The monitoring process incorporates hormones, neuropeptides, minerals, amino acids and sugar. Their presence and levels are detected via a vast network of membrane receptors.

Receptors provide the sites for the various ions, metabolites, hormones and proteins to bind to. This binding or information is processed along with all the visual, auditory, olfactory, gustatory and proprioceptive signals that emanate from the five senses.

 

The hypothalamus is responsible for regulating appetite, mood, and pleasure. Drugs, foods, images, smells and thoughts can either stimulate appetite or repress it. They produce their effects through this universal phenomenon of receptor binding.

Specifically, a stimulus (image, sight, smell, taste, thought or chemical) signals a series of events that culminate in the binding of their respective receptors in the hypothalamus.

The neural chemistry of the hypothalamus is thus a prime target for pharmaceutical companies to develop appetite supressing drugs.

 

Hypothalamus receptors bind to native ligands. These bindings regulate appetite. The level of hunger in an individual is based on the body’s set point, which in turn is based on fat levels inside of specific cells.

Fat is monitored an appetite adjusted by a group of specialized proteins. Leptin, orexin neuropeptide Y and ghrelin are neuropeptides that determine how much eating is needed based on the amount of energy stored in the body.

Dysfunction in receptor function leads to weight gain.

Leptin is a small hormone produced inside adipose (fat). The more fat it contains, the higher the amount of leptin that is released. The small peptide then circulates to the brain where its presence and level is monitored by nerve cells in the hypothalamus that are involved with energy regulation.

Once bound, leptin represses the urge to eat.  Binding of leptin to receptors indicates that enough energy is stored and producing a natural feeling of not being hungry.

 

While leptin is produced inside of fat cells, its effect is in the brain where it suppresses appetite and the urge to eat.

 

Leptin is a weight loss neuropeptide. In addition to directly repressing hunger, it also blocks the receptor site used by the neuropeptides that stimulate appetitie.

Notable is leptin’s ability to bind to the anandamide receptor, which the cannabinoids of marijuana and neuropeptide Y bind to; two compounds known to stimulate hunger and eating. This is the molecular mechanism of the munchies and why many patients can benefit from marijuana.

When leptin occupies these sites, it blocks the amadamide sites, therebye repressing the drive to eat. Leptin level drop following the consumption of fructose rich meals. This may explain the overeating seen in kids since the 1980’s when fructose was introduced as a sweetener. Leptin analogues are now under investigation as a possible therapy for obesity.

Grelin, another neuropeptide involved with regulating appetitie, is manufactured by the cells lining the stomach. Ghrelin counters the effect of leptin.  Once ghrelin reaches the brain, it binds to receptors to stimulate appetite. Ghrelin levels are high just before meals, which promotes the desire to eat. Ghrelin levels decrease as the meal is consumed, signalling and end to eating. Due to its promotion of appetite, ghrelin has become a hot target for pharmaceutical intervention.

 

Eating Addiction

Foods are composed of nutrients, fiber, and a library of compounds. Taste, color and odor molecules are wrapped inside a plant’s cells. These physical characteristics are determined by the chemical library found in the whole plant.

These plant compounds or ligands, interact with sensory receptors to initiate an activity. These olfactory, ocular  and gustatory stimuli are then interpreted by the brain to produce the sensations of smell, sight and taste.

Eating addictions are not very different from drug addiction. They operate on the same receptor-ligand binding phenomenon that drugs, hormones and neurotransmitters do. Exercise is another type of addiction, a healthy addiction

Fast-food restaurants, comfort snacks and prepared food capitalize on food addiction by serving and providing food that is high in fat, a substance that is very addictive to the palate.

The signals are sent from the taste buds in the mouth to be interpreted by the hypothalamus where they are monitored, computed and evaluated via a series of interactions between neuropeptides, hormones and neurotransmitters.

Leptin, orexin, neuropeptide Y, ghrelin, serotonin and dopamine bind to a number of receptors involved in energy regulation, satiety and pleasure. These bindings occur in the Ventral Tegmental area (VTA) of the brain. The VTA responds to fat food and other addictive substances by producing more receptors, thus increasing the potential of addiction.

Leptin for example, binds to neurons in the brain involved with energy regulation thereby shutting down the urge to eat. Despite the sufficient production of leptin, obese people continue to eat.

The reason they overeat is similar to why adult onset or Type II (nutritional) diabetics fail to metabolize glucose even though they secrete an adequate amount of insulin.

Obese diabetics produce resisten, another peptide produced by fat cells. Resistin reduces the sensitivity to insulin, causing cells to become resistant to the hormone. In both instances, the receptor no longer recognizes and responds to its proper ligand (leptin and insulin) because its active site has been occupied by an alternative ligand.  In the case of leptin, the alternative ligand is one of a series of neuropeptides.

Orexin, named after the Greek word for appetite, are hunger-stimulating neuropeptides, produced in the hypothalamus. Orexin binds to G-protein coupled receptors setting off a series of events that produce an increase in appetite. Orexin opposes the action of leptin.

 

Over production of orexin induces overeating and sleepiness.

Neuropeptide Y is a neurotransmitter in the hypothalamus, involved with energy regulation. Neuropeptide Y increases the urge to eat and the avoidance of physical activity. High levels of this peptide is correlated with increased food intake and decreased expenditure of energy. Stress, high fat, and high sugar levels stimulate the release of neuropeptide Y.

Neuropeptide Y opposes the actions of leptin. Both in the satiety neurons in the hypothalamus and on sites where leptin causes the repression of appetite. This explains the experience of the obese who fail to stop eating despite adequate amounts of leptin.

 

Overproduction of Neuropeptide Y is linked to obesity.

Repression of Neuropeptide Y may lead to weight loss.

 

Both orexin and Neuropeptide Y stimulates appetite and produces an urge to eat. Leptin on the other hand, prevents the synthesis of Neuropeptide Y.