Obesity, a complex and multifactorial syndrome, represents a high burden for public health systems worldwide. The intricate relationship between serotonin and weight regulation has become a focal point in understanding and addressing obesity. Serotonin, a key neurotransmitter, plays a pivotal role in feeding behavior and weight regulation. This article explores the multifaceted connection between serotonin levels and weight management, examining how this neurotransmitter influences appetite, metabolism, and overall well-being.
The Serotonin-Carbohydrate Connection: A Double-Edged Sword
The "jolly fat" hypothesis suggests that overweight individuals tend to be happier, with studies showing obese men less likely to display symptoms of depression than their normal-weight counterparts. Population-based studies support this. However, this isn't always the case, especially for women in industrialized societies, who often face stigmatization due to their weight.
Obese people may eat certain foods that reduce or eliminate depression altogether, specifically carbohydrates. Carbohydrate craving can be a form of self-medication, temporarily relieving depression by increasing serotonin levels in the brain.
When you eat carbohydrates, they cause the production of insulin, which allows an amino acid called tryptophan to enter the brain. Tryptophan stimulates the production of the neurotransmitter called serotonin, which makes us feel good. This mood change is often subtle, occurring subconsciously.
While carbohydrates boost serotonin, excessive consumption leads to weight gain. Many obese people have "serotonin hunger," overeating high-carbohydrate snacks for their serotonin-mediated psychopharmacological effects, not necessarily out of hunger or taste preference.
Read also: Weight Loss Guide Andalusia, AL
Most snack foods, such as potato chips, pastries, and sweets, are carbohydrates. The subconscious desire to feel good causes people to eat more carbohydrates. That same desire causes people to eat more food than necessary, which becomes a habit. The calories in excess of our energy needs are stored as fat. (Protein does not stimulate production of serotonin, and people rarely over-indulge in protein-type foods.)
Serotonin's Role in Appetite Control and Energy Balance
Serotonin in the brain affects what we choose to eat, and it creates feelings of “fullness.” If your serotonin levels are unbalanced or malfunctioning, you may be predisposed to obesity. Tending to binge on carbohydrates in an unconscious attempt to boost your serotonin levels so you have that “feel-good” attitude. Serotonin significantly influences appetite control and energy homeostasis through multiples pathways, including insulin resistance, high-fat diets, gut microbiota, low-grade inflammation, interferences with tryptophan metabolism, psychiatric modifications, genetic alterations of serotonin receptors, serotonin implications in eating behavior, and neurohormonal regulation of appetite.
Serotonin influences both the homeostatic and hedonic circuits of food intake regulation. In the homeostatic circuitry, serotonergic signaling contributes to the integration of metabolic signals that convey the body's energy status and facilitates the ability to suppress food intake when homeostatic needs have been met. In the hedonic circuitry, serotonergic signaling may reduce reward‐related, motivational food consumption.
The Science Behind Serotonin and Weight
Basically, it all happens in the brain. When you eat carbohydrates, they cause the production of insulin, which allows an amino acid called tryptophan to enter the brain. Tryptophan stimulates the production of the neurotransmitter called serotonin.
Serotonin makes us feel good. Apparently, people who are chronically overweight have become subconsciously addicted to the serotonin-stimulated, happy, comfortable feeling.
Read also: Beef jerky: A high-protein option for shedding pounds?
Fen-phen and Redux, the two diet drugs pulled from the market, worked effectively as weight-loss drugs because they caused an increase in the production of serotonin. With plenty of serotonin in the brain, people don’t have much desire for carbohydrates and don’t eat as much, so they lose weight.
Dr. Richard J. Wurtman, a scientist at Massachusetts Institute of Technology, reported in the medical journal Obesity Research that animals given serotonin-releasing drugs would not overindulge in carbohydrates when given the choice of carbohydrates and proteins. This indicates that elevated serotonin levels help decrease overconsumption of refined carbohydrates, which leads to overall reduction of fat-producing foods, thereby reducing calorie-related obesity.
A Closer Look at Serotonin's Pathways
Serotonergic pathways involved in regulation of food intake. Most ascending serotonergic projects arise from the dorsal and medial raphe nuclei. Serotonin signaling is involved in multiple brain regions that play a role in the homeostatic and hedonic circuits of food intake regulation, including the raphe nuclei, nucleus tractus solitarius (NTS), parabrachial nucleus (PBN) of the brainstem and the arcuate nucleus (ARC), paraventricular nucleus (PVN), ventral medial nucleus (VMN), dorsomedial nucleus (DMN), and lateral hypothalamic area (LHA) of the hypothalamus.
The activity of serotonergic neurons in the DRN increases directly after food intake, whereas the activity of serotonergic neurons in the MRN does not. Raphe nuclei serotonergic neurons are under regulatory control of central and peripheral input. The gastrointestinal hormones cholecystokinin (CCK) and glucagon‐like peptide 1 (GLP1) are secreted from the gastrointestinal tract in response to nutrient ingestion.
The ARC in the hypothalamus and NTS in the brainstem are among those brain regions that receive serotonergic projections from the DRN. The ARC is in close proximity to the third ventricle and has a leaky blood-brain barrier (BBB). It is optimally equipped to read out circulating nutritional and hormonal signals. The importance of POMC neurons in the regulation of food intake has been well established. The AgRP/NPY neurons in the ARC mediate an opposite, orexigenic effect via a dual mechanism.
Read also: Inspiring Health Transformation
The PVN receives dense projections from POMCARC/NTS and AgRP/NPY neurons. Melanocortin receptors are highly expressed in the PVN, and the importance of the melanocortin pathway downstream of POMCARC/NTS and AgRP/NPY neurons is illustrated by several lines of evidence.
It is likely that other and/or more specific functions of the VMN have yet to be discovered. It is not clear whether serotonin signaling is involved. It may thus be possible for serotonin signaling to exert some anorexigenic effects through the DMN. Another neuronal population in the LHA expresses melanin‐concentrating hormone (MCH).
It is unknown how thalamic serotonin signaling is functionally involved in the regulation of feeding behavior. Weight loss and weight gain also affect thalamic SERT availability, but these effects are dependent on meal timing during weight loss and meal composition during weight gain. Serotonin signaling may contribute to reported favorable effects of meal timing on weight maintenance.
The mesolimbic system, including the VTA, the nucleus accumbens (NAc) of the ventral striatum, and the CeA, is sometimes referred to as the reward pathway. These regions have also been proposed to partake in the interaction between homeostatic and hedonic regulation of food intake. Most dopaminergic projections to the mesolimbic brain areas originate from the VTA. Just like the hypothalamic nuclei of the homeostatic system, the VTA itself is innervated by serotonergic neurons from the DRN. Serotonergic signaling in the VTA may decrease the hedonic drive for eating behavior, primarily via GABAergic inhibition of VTA dopaminergic neurons.
The NAc, located in the ventral part of the striatum, is a major target for downstream VTA dopaminergic projections. A proposed hypothalamic-thalamic-striatal axis links the NAc to the homeostatic system. This axis would allow hypothalamic serotonergic signaling to influence NAc dopaminergic signaling, but its precise role remains unclear.
When Serotonin Goes Wrong: The Link to Obesity
Failure to appropriately suppress food intake when body energy stores are sufficient results in the (over)consumption of food beyond nutritional needs and, subsequently, weight gain. Serotonergic signaling fulfills an important role in the regulation of food intake, disruption in serotonergic signaling may contribute to the pathogenesis of disturbed feeding behavior in individuals with chronic overweight or obesity.
Obesity results from an energy intake that exceeds energy expenditure. Attenuated homeostatic inhibition and/or increased hedonic drive for energy consumption has been postulated to contribute to the consumption of food beyond homeostatic needs. Human obesity is associated with reduced serotonergic signaling. Early changes in serotonergic signaling occur during overconsumption, and these may contribute to the onset and/or persistence of overweight and obesity.
Diet‐induced changes in serotonergic signaling precede the onset of obesity. In humans, it is impossible to study the central serotonin system in vivo directly. Whether these findings are the consequence or cause of obesity remains a point of discussion.
Lower serotonin levels are linked to higher rates of anxiety and depression, but this effect might cause overeating as a coping strategy. However, this can lead to a vicious cycle whereby eating more food further lowers serotonin levels, worsening psychological distress and obesity. There are several hormones involved in appetite regulation, such as leptin, ghrelin, peptide YY, glucagon-like peptide 1, insulin, and glucagon. Their release is modulated by food composition, fasted eating, and low-grade inflammation, and they modulate the serotonergic and dopaminergic systems.
Increased levels of Prevotella spp. in the microbiome lead to dysregulations and insulin resistance through BCAA formation. This specific gut microbiota population in obese patients, rich in Prevotella spp. and Bacteroides spp., influences the conversion of TRP into serotonin, thereby diminishing serotonin levels, leading to increased appetite signaling and weight gain. Dietary factors, particularly increased protein intake, lead to high levels of TRP in plasma, suggesting that dysbiosis induced by dietary habits interfere with serotonin levels through the gut microbiota. Fiber-rich diets can increase the synthesis of short-chain fatty acids (SCFAs), such as butyrate, which has been demonstrated to improve insulin sensitivity and serotonin signaling. This implies that dietary changes targeted at enhancing gut health may positively impact serotonin levels, which in turn may influence hunger control and weight management. Additionally, the location and function of enterochromaffin cells (ECs) may be changed in obese people, which can result in dysregulated hormone release and diffi…
A Safer Approach: Natural Ways to Boost Serotonin
But drugs are not the only substances that increase serotonin in the brain. An extract from the plant Hypericum perforatum has been used for many years in Europe as an antidepressant. Instead of flooding the body with dangerous drugs to increase serotonin, Hypericum increases serotonin naturally by inhibiting an enzyme in the brain called monoamine oxidase (MAO). This enzyme destroys serotonin and norepinephrine (another important brain neurotransmitter).
By taking Hypericum, you get the same positive end result as with the deadly diet drugs~more serotonin and less desire for carbohydrates but without the dangerous side effects. Dr. S. Perovic reported in the medical journal Drug Research that Hypericum also keeps serotonin active between meals to further prevent snacking.
Most people view dieting and losing weight as a difficult chore that will continue to make them miserable until they stop. Hypericum has just the opposite effect. You’ll feel happy, comfortable, and won’t have to fight the cravings and hunger pains. Dr. E.U. Vorbach conducted a double-blind study in which half the people were given a popular antidepressant drug and half were given Hypericum. Hypericum reduced depression by 56%, whereas the drug only reduced it by 45%.
Another substance critical to maintaining elevated mood while you are dieting is pyridoxine. This is one of the most difficult vitamins to get from food because cooking and refining food destroys it. Severe deficiency of pyridoxine usually causes not only depression and other nerve problems, but also sores that don’t heal quickly, or other skin disorders. Pyridoxine must be taken with adequate magnesium and all the B vitamins to be used by the body.
Besides maintaining uplifted spirits for successful dieting, you also have to get rid of that excess fat. The body does this through a process called ‘thermogenesis:’ Thermogenesis converts stored fat to soluble lipids, which are then burned off by body heat.
Two nutrients must be present to cause thermogenesis. The nutrient DLphenylalanine (DLPA) causes the production of tyrosine. Tyrosine makes three neurotransmitters for the brain: epinephrine, dopamine, and norepinephrine. Norepinephrine triggers thermogenesis. A second nutrient, inositol hexanicotinate (a form of a B vitamin) assists in breaking down the fat into soluble lipids. Dr. Neil Stone, a professor at Northwestern University School of Medicine, found that hexanicotinate reduced LDL (bad cholesterol) by 17%, while increasing HDL (good cholesterol) by almost 3O% a plus for dieters! Essentially, what you need is a balanced ‘wellness” formula, combined with regular exercise and a healthy diet, which includes lots of fruits and vegetables.
Serotonin's Impact on Weight Loss After Surgery
Surgical interventions, such as laparoscopic sleeve gastrectomy (LSG), are frequently associated with significant weight loss. However, the initiation and maintenance of this weight reduction are multifaceted processes influenced by genetic, psychological, behavioral, dietary, and metabolic factors.
Weight loss maintenance after LSG is influenced by various hormones, including ghrelin, leptin, insulin, and peptide YY (PYY). LSG leads to a marked reduction in ghrelin levels, attributed to removing a portion of the stomach responsible for its production. Patients experience significant weight loss after LSG, significantly reducing leptin levels. This decline is associated with decreased energy expenditure, a common outcome for individuals post-LSG. Concurrently, LSG has an immediate positive impact on glucose metabolism and insulin sensitivity, even before significant weight loss occurs.
Individuals might experience significant challenges in weight loss maintenance post-LSG due to factors such as metabolic adaptation, dietary factors, and psychological elements. Eating behaviors can further be influenced by psychological factors such as emotional eating, depression, and stress. These elements pose significant challenges to sustaining weight loss in patients who have undergone LSG.
Given the challenges associated with maintaining weight loss after LSG, various interventions and strategies have been developed to support patients' weight management efforts, including psychological support, nutritional guidance, physical activity promotion, pharmacotherapy, and revisional surgery. Counseling services are essential for helping patients manage emotional factors that can affect eating habits. In nutritional guidance, patients are exposed to meal planning and diet control guidelines, which help them develop sustainable eating habits. For some patients, pharmacological interventions may be necessary. These involve prescribing medications that help regulate appetite and reduce cravings under careful medical supervision.
Serotonin, commonly referred to as the “feel-good” neurotransmitter, plays a crucial role in the body that extends beyond mood regulation. Since the hormone influences the appetite of individuals, it is a key contributor to weight regulation. When the brain signals for the release of serotonin, it triggers the activation of cells in the stomach responsible for producing this hormone. This activation occurs through the binding of serotonin to specific receptors known as 5-hydroxytryptamine receptor 2C (5-HT2C) located in the hypothalamus section of the brain. Activated 5-HT2C ultimately reduces appetite and increases the feeling of satisfaction. As such, higher serotonin levels are associated with better appetite control, which is key in weight loss maintenance. Research indicates that laparoscopic sleeve gastrectomy can influence the production of serotonin, resulting in elevated levels of serotonin circulating in the body.
Beyond its role in appetite control, serotonin is crucial in regulating emotions and mental well-being. A decrease in serotonin levels is consistently linked to increased anxiety and depression, potentially leading to emotional eating and subsequent weight gain. The ability of LSG to modulate serotonin sensitivity positively impacts patients' quality of life, reducing mood-related issues and, consequently, diminishing the likelihood of emotional eating. It is noteworthy that emotional eating can have dual effects on weight, as individuals experiencing depression may sometimes eat less, contributing to weight loss.
The emerging roles of serotonin in weight regulation and its impacts in post-LSG have created a growing interest in developing therapeutic strategies to enhance weight loss maintenance. Among the strategies developed include pharmacological interventions, dietary approaches, and lifestyle modifications. Strategies that promote overall well-being, such as stress reduction, regular physical activity, and adequate sleep, can indirectly influence serotonin levels and mood. Incorporating these lifestyle changes post-LSG may contribute to better weight maintenance outcomes. Furthermore, dietary choices play a significant role in affecting serotonin production. Foods rich in tryptophan, the amino acid precursor to serotonin, can support serotonin synthesis. Thus, incorporating a balanced diet that includes such foods post-LSG could naturally enhance serotonin levels. While research continues research on potential medications targeting serotonin receptors, some drugs, such as selective serotonin reuptake inhibitors (SSRIs), have shown effectiveness in managing appetite and mood, which are crucial for maintaining long-term weight loss.
Peripheral Serotonin: A Different Perspective
According to a study published in Natural Medicine, there are 2 types of serotonin. The type that is known for its effects on mood and appetite only accounts for 5% of serotonin in the body, while the other 95%, called peripheral serotonin, plays a role in obesity. Apparently, too much peripheral serotonin in the blood inhibits the brown fat that burns energy and glucose to make heat, which leads to obesity and the development of diabetes.
A previous study showed that preventing the formation of peripheral serotonin results in more active brown fat. In this more recent study, tryptophan hydroxylase (Tph1)-the enzyme responsible for the production of serotonin—was blocked or removed in mice that were fed a high-fat diet. This resulted in the improved ability of brown fat to burn more calories, thus protecting the mice from obesity and its complications.
Study co-author Waliul Khan stated that the high-fat diet prevalent in the United States is “an environmental cue that could be causing higher serotonin levels in our body.” In addition, Steinberg noted that preventing the production of peripheral serotonin will not affect serotonin in the brain, unlike earlier weight-loss drugs that curb appetite yet alter such serotonin levels, leading to an increased risk of depression and suicidality.
The same group of researchers are currently working on developing an “enzyme blocker” medication that will inhibit Tph1, thereby decreasing the amount of serotonin in the blood and combating obesity.
The Future of Serotonin-Based Therapies
On the basis of the evident role of serotonergic signaling in feeding behavior and translational observations supporting reduced serotonergic signaling in human obesity, the stimulation of central serotonergic signaling emerged as a therapeutic target for obesity well over a decade ago. Initially, fenfluramine and, later, dexfenfluramine and sibutramine were successfully marketed as obesity treatments. Unfortunately, the success of serotonergic drugs in the treatment of obesity has so far been limited by peripheral side effects due to the stimulation of serotonin receptors in peripheral tissues.
Several serotonergic drugs have shown promising results in humans with obesity, but they have also been associated with severe side effects; further research is required to determine if this system can be safely targeted in humans with obesity.
While weight-loss therapies have improved over time, serotonergic therapies remain among the leading approaches for effective weight management with new targets continually being discovered.
Serotonin Synthesis, Storage, and Metabolism
5-HT is synthesized from the essential amino acid tryptophan, which is obtained from food. 5-HT is produced in both the peripheral and central nervous systems, and cannot cross the blood-brain barrier [18]. The conversion of tryptophan to 5-hydroxytryptophan is facilitated by the rate-limiting enzyme tryptophan hydroxylase (TPH) [19, 20]. TPH exists in two isoforms, TPH1, found in peripheral serotonin-producing tissues such as the gut, pineal gland, spleen, and thymus, and TPH2 is found in central serotonin-producing neurons like the raphe nuclei [21]. Subsequently, 5-hydroxytryptophan is converted to 5-hydroxytryptamine (5-HT or sertonin) by aromatic l-amino acid decarboxylase [22].
In the brain, 5-HT is stored in vesicles until exocytosis is triggered, leading to its release into the synaptic cleft. In the periphery, the gut is the primary site of 5-HT synthesis; however, platelets will uptake 5-HT from the plasma via the serotonin transporter (SERT), making platelets the fundamental regulators of plasma 5-HT concentration [23]. Platelets store 5-HT in dense granules and release 5-HT into circulation upon stimulation. Once 5-HT is no longer bound to one of its receptors, it is transported back into cells via SERT [24]. Following reuptake, 5-HT is rapidly metabolized by monoamine oxidase into 5-hydroxyindole acetaldehyde, which is further broken down into 5-hydroxindile acetic acid (5-HIAA). The measurement of 5-HIAA, the major metabolite of 5-HT, in urine is a commone and non-invasive method for determining 5-HT levels [25].
tags: #serotonin #and #weight #loss #connection