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Table of Contents
Introduction
We tend to think that overweight people who eat too much lack willpower. We couldn’t be more wrong.
Hunger is controlled by a complex interaction between hormones, neurotransmitters, and other physiological factors. The interactions between these hormones and neurotransmitters are complex and can be influenced by a variety of factors, such as stress, sleep, exercise, and medications. Additionally, external factors like food availability, social, cultural influences, and psychological factors can also impact hunger.
In this article, I present the main principles that regulate hunger and reveal how a bad diet or low-calorie diets can deregulate this precision machine.
The main molecules controlling our hunger
Neuropeptide Y
Neuropeptide Y (NPY) is a neurotransmitter that is involved in regulating feeding behaviour, including appetite stimulation and food intake. NPY is primarily produced by neurons located in the hypothalamus, which is a region of the brain that regulates food intake, appetite, energy expenditure, and other vital functions.
NPY stimulates hunger by acting on specific receptors in the hypothalamus and other regions of the brain that regulate feeding behaviour. NPY receptors are expressed on neurons that produce other neurotransmitters involved in appetite regulation, such as agouti-related protein (AgRP) and melanin-concentrating hormone (MCH).
When NPY binds to its receptors on these neurons, it triggers a cascade of intracellular signalling pathways that ultimately lead to the activation of orexigenic (appetite-stimulating) pathways and the inhibition of anorexigenic (appetite-suppressing) pathways. Specifically, NPY promotes the expression of AgRP and MCH, which stimulate feeding behaviour and suppress energy expenditure.
In addition, NPY also acts on other areas of the brain involved in reward and motivation, leading to increased food-seeking behaviour and appetite.
NPY levels are regulated by a variety of factors, including nutrient availability, stress, and hormonal signals such as ghrelin and insulin (see below). For example, when blood glucose levels are low, NPY levels are increased, leading to an increase in appetite and food intake. Additionally, chronic stress has been shown to increase NPY levels, potentially leading to overeating and weight gain.
Ghrelin
Ghrelin is a hormone produced in the stomach that stimulates hunger. Ghrelin levels increase when the stomach is empty and decrease when it is full. Ghrelin stimulates hunger by acting on the hypothalamus.
Ghrelin binds to a specific receptor called the growth hormone secretagogue receptor (GHSR) in the hypothalamus. This binding activates a signalling pathway that ultimately leads to the release of neuropeptides that stimulate appetite.
This signalling pathway involves the activation of several intracellular signalling molecules, including cyclic AMP (cAMP) and protein kinase A (PKA). Activation of PKA leads to the activation of a transcription factor called cAMP response element-binding protein (CREB), which regulates the expression of genes involved in appetite regulation.
Ghrelin also stimulates the release of the neurotransmitter dopamine, which is known to play a role in reward processing and motivation. This may contribute to the pleasurable feeling associated with eating and promote food-seeking behaviour.
Leptin
Leptin is a hormone produced by fat cells that helps regulate body weight by suppressing hunger and increasing energy expenditure. The mechanism by which leptin controls hunger at the molecular level involves signalling pathways in the hypothalamus.
When fat cells release leptin into the bloodstream, the hormone travels to the hypothalamus and binds to specific receptors called leptin receptors. This binding triggers a series of signalling events that ultimately result in the suppression of appetite.
One of the key signalling pathways activated by leptin is the JAK-STAT pathway, which involves the activation of the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) proteins. When leptin binds to its receptor, it activates JAK, which then adds a phosphate group to STAT proteins. The phosphorylated STAT proteins then form dimers and translocate to the nucleus, where they activate the expression of genes involved in appetite suppression and energy expenditure.
Another important signalling pathway activated by leptin is the PI3K-Akt pathway, which involves the activation of phosphatidylinositol 3-kinase (PI3K) and Akt proteins. This pathway plays a role in the regulation of glucose metabolism and insulin sensitivity, as well as in the control of food intake. Activation of the PI3K-Akt pathway by leptin leads to the repression of NPY and AgRP producing neurons, which are known to stimulate appetite.
Insulin
Insulin is a hormone produced by the pancreas that is primarily involved in regulating glucose levels in the body. However, it also plays a role in regulating appetite and satiety. Insulin can suppress appetite by acting on specific areas of the brain that regulate feeding behaviour.
Insulin suppresses appetite by activating pro-opiomelanocortin (POMC) neurons in the hypothalamus. Insulin binds to receptors on POMC neurons, triggering a series of intracellular signalling pathways that ultimately lead to the activation of an enzyme called AMP-activated protein kinase (AMPK). AMPK acts as a cellular energy sensor, detecting changes in the levels of energy substrates like glucose and fatty acids. When AMPK is activated in POMC neurons, it suppresses appetite by decreasing the expression of NPY and increasing the expression of appetite-suppressing hormones like alpha-melanocyte-stimulating hormone (α-MSH) and corticotropin-releasing hormone (CRH).
In addition to its effects on POMC neurons, insulin can also stimulate the release of leptin.
Other hormones regulating appetite
Peptide YY (PYY), cholecystokinin (CCK), and glucagon-like peptide-1 (GLP-1) are hormones that are secreted by the gastrointestinal tract in response to food intake. These hormones play a role in regulating appetite and satiety by signalling to the brain that food has been consumed, leading to a decrease in hunger and food intake.
PYY, CCK, and GLP-1 suppress hunger by acting on receptors in the brain that regulate feeding behaviour. Specifically, these hormones bind to receptors in the hypothalamus and other regions of the brain that are involved in appetite regulation, such as the nucleus tractus solitarius (NTS).
When PYY, CCK, and GLP-1 bind to their receptors in the hypothalamus, they activate appetite-suppressing pathways and inhibit appetite-stimulating pathways. For example, GLP-1 stimulates the release of insulin from pancreatic beta cells, which suppresses appetite and promotes satiety. In addition, GLP-1 also inhibits the release of glucagon, a hormone that promotes the release of glucose from the liver, further contributing to the satiety effect.
CCK, on the other hand, is released by the small intestine in response to the presence of food, especially fat. CCK signals the brain to decrease food intake by reducing gastric emptying and increasing satiety. Similarly, PYY is secreted by the small intestine and colon in response to food intake and signals to the brain to decrease appetite and food intake.
Mechanisms affecting appetite regulation
Multiple factors can deregulate hormones and neurotransmitters involved in appetite regulation resulting in overeating or undereating and contributing to the development of obesity or eating disorders.
Some of these factors include Insulin resistance, chronic inflammation, sleep deprivation, chronic stress, certain medications, such as antidepressants, antipsychotics, and corticosteroids, genetic variations and, last but not least, lifestyle factors including poor diet quality and lack of physical activity.
For example, genetic factors or chronic inflammation can induce leptin resistance, a condition in which the body becomes less responsive to the appetite-suppressing effects of leptin. Similarly, chronic stress can lead to overexpression of NPY and/or dysregulation of ghrelin, the latter also happening in response to sleep deprivation.
All these examples highlight how easily our appetite can be altered. In the following, we will focus on an aspect that is of particular concern to nutritionists, how the quality of our food can alter the mechanisms that control hunger.
Impact of poor diets on satiety control
Poor diet can alter how our hunger is controlled in several ways.
First, indirectly, by contributing to chronic inflammation or by altering the gut microbiome provoking an imbalance called dysbiosis. Both conditions are known to interfere with the action of satiety hormones and to lead to dysregulated appetite control.
A diet, high in processed foods, can impair the release of the hormones involved in gut signalling, CCK, PYY and GLP-1 and, therefore, preventing the brain to receive the signals of satiety.
Moreover, and in a similar way than genetic factors or chronic inflammation, sugar-rich and high processed foods can lead to leptin resistance, which, then, will interfere with the signalling pathways involved in satiety control.
Finally, a diet high in saturated fats can dysregulate the endocannabinoid system, a system playing a role in regulating appetite and food intake, leading to increased appetite and overeating.
Making dietary changes to include more whole foods, fibre, and healthy fats can help restore balance to these systems and promote healthy satiety control.
Poor diet, epigenetic and satiety control
Poor diet can impact satiety control at the epigenetic level. Epigenetics refers to modifications to DNA or associated proteins that can influence gene expression without changing the underlying DNA sequence.
DNA methylation is a process by which methyl groups are added to DNA, typically at cytosine residues in CpG dinucleotides. DNA methylation can alter gene expression by affecting the binding of transcription factors or by recruiting proteins that modify chromatin structure. Studies have shown that DNA methylation can affect the expression of genes involved in satiety control, such as the leptin gene.
Histones are proteins that package DNA into chromatin, and modifications to histones can affect gene expression by altering chromatin structure. Histone modifications have been shown to affect the expression of genes involved in appetite regulation, such as the AgRP gene.
Non-coding RNA molecules, such as microRNAs and long non-coding RNAs, can regulate gene expression by binding to messenger RNA molecules and interfering with their translation into protein. Non-coding RNAs have been implicated in the regulation of appetite and energy balance, and their dysregulation has been associated with obesity and metabolic disorders.
Low-calorie diet and satiety control
A hypocaloric (low-calorie) diet can alter satiety and hunger control in several ways. When you consume fewer calories than your body needs, it can trigger a cascade of physiological responses that affect appetite regulation.
For example, it can trigger an increase in hunger hormones such as ghrelin.
A hypocaloric diet can also reduce the production of satiety hormones such as CCK, PYY, and GLP-1 leading to decreased satiety and increased hunger.
It can alter the composition of the gut microbiome, promoting dysbiosis, which, as discussed above, can interfere with satiety control.
This diet can also impair the reward pathways in the brain that are involved in regulating food intake. When you consume fewer calories than your body needs, it can reduce the release of dopamine, a neurotransmitter involved in reward and motivation. This can lead to decreased feelings of pleasure and satisfaction from food, which can contribute to increased hunger and cravings.
Conclusion
In summary, it is important to realise that our attraction to food is not just a matter of willpower. When you can’t control your weight and your health deteriorates, the last thing you want to do is feel guilty.
First, you have to understand why you are always hungry and how to adapt your lifestyle and diet to change things and get out of a negative spiral.