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Current Opinion in Endocrinology,... Jun 2024Various gut hormones interact with the brain through delicate communication, thereby influencing appetite and subsequent changes in body weight. This review summarizes... (Review)
Review
PURPOSE OF REVIEW
Various gut hormones interact with the brain through delicate communication, thereby influencing appetite and subsequent changes in body weight. This review summarizes the effects of gut hormones on appetite, with a focus on recent research.
RECENT FINDINGS
Ghrelin is known as an orexigenic hormone, whereas glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), postprandial peptide YY (PYY), and oxyntomodulin (OXM) are known as anorexigenic hormones. Recent human studies have revealed that gut hormones act differently in various systems, including adipose tissue, beyond appetite and energy intake, and even involve in high-order thinking. Environmental factors including meal schedule, food contents and quality, type of exercise, and sleep deprivation also play a role in the influence of gut hormone on appetite, weight change, and obesity. Recently published studies have shown that retatrutide, a triple-agonist of GLP-1, GIP, and glucagon receptor, and orforglipron, a GLP-1 receptor partial agonist, are effective in weight loss and improving various metabolic parameters associated with obesity.
SUMMARY
Various gut hormones influence appetite, and several drugs targeting these receptors have been reported to exert positive effects on weight loss in humans. Given that diverse dietary and environmental factors affect the actions of gut hormones and appetite, there is a need for integrated and largescale long-term studies in this field.
Topics: Humans; Gastrointestinal Hormones; Appetite Regulation; Obesity; Cholecystokinin; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Peptide YY; Oxyntomodulin; Animals; Ghrelin; Appetite
PubMed: 38511400
DOI: 10.1097/MED.0000000000000859 -
Nature Dec 2023The termination of a meal is controlled by dedicated neural circuits in the caudal brainstem. A key challenge is to understand how these circuits transform the sensory...
The termination of a meal is controlled by dedicated neural circuits in the caudal brainstem. A key challenge is to understand how these circuits transform the sensory signals generated during feeding into dynamic control of behaviour. The caudal nucleus of the solitary tract (cNTS) is the first site in the brain where many meal-related signals are sensed and integrated, but how the cNTS processes ingestive feedback during behaviour is unknown. Here we describe how prolactin-releasing hormone (PRLH) and GCG neurons, two principal cNTS cell types that promote non-aversive satiety, are regulated during ingestion. PRLH neurons showed sustained activation by visceral feedback when nutrients were infused into the stomach, but these sustained responses were substantially reduced during oral consumption. Instead, PRLH neurons shifted to a phasic activity pattern that was time-locked to ingestion and linked to the taste of food. Optogenetic manipulations revealed that PRLH neurons control the duration of seconds-timescale feeding bursts, revealing a mechanism by which orosensory signals feed back to restrain the pace of ingestion. By contrast, GCG neurons were activated by mechanical feedback from the gut, tracked the amount of food consumed and promoted satiety that lasted for tens of minutes. These findings reveal that sequential negative feedback signals from the mouth and gut engage distinct circuits in the caudal brainstem, which in turn control elements of feeding behaviour operating on short and long timescales.
Topics: Appetite Regulation; Brain Stem; Eating; Feedback, Physiological; Food; Neural Pathways; Neurons; Prolactin-Releasing Hormone; Satiation; Solitary Nucleus; Stomach; Taste; Time Factors; Animals; Mice
PubMed: 37993711
DOI: 10.1038/s41586-023-06758-2 -
Adipocyte Dec 2023Adipokines are proteins secreted by adipose tissue to regulate glucolipid metabolism and play vital roles in our body. Different adipokines have more than one endocrine...
Adipokines are proteins secreted by adipose tissue to regulate glucolipid metabolism and play vital roles in our body. Different adipokines have more than one endocrine function and be divided into several different categories according to their functions, including adipokines involved in glucolipid metabolism, the inflammatory response, insulin action, activation of brown adipose tissue (BAT) and appetite regulation. Multiple adipokines interact with each other to regulate metabolic processes. Based on the recent progress of adipokine research, this article discusses the role and mechanism of various adipokines in glucolipid metabolism, which may provide new ideas for understanding the pathogenesis and improving the treatment of various metabolic diseases.
Topics: Adipokines; Glucose; Lipid Metabolism; Adipose Tissue; Adipose Tissue, Brown; Energy Metabolism; Leptin
PubMed: 37077042
DOI: 10.1080/21623945.2023.2202976 -
Journal of Neuroendocrinology Sep 2023Serotonin is a neurotransmitter that is synthesized and released from the brainstem raphe nuclei to affect many brain functions. It is well known that the activity of... (Review)
Review
Serotonin is a neurotransmitter that is synthesized and released from the brainstem raphe nuclei to affect many brain functions. It is well known that the activity of raphe serotonergic neurons is changed in response to the changes in feeding status to regulate appetite via the serotonin receptors. Likewise, changes in volume status are known to alter the activity of raphe serotonergic neurons and drugs targeting serotonin receptors were shown to affect sodium appetite. Therefore, the central serotonin system appears to regulate ingestion of both food and salt, although neural mechanisms that induce appetite in response to hunger and sodium appetite in response to volume depletion are largely distinct from each other. In this review, we discuss our current knowledge regarding the regulation of ingestion - appetite and sodium appetite - by the central serotonin system.
Topics: Appetite; Sodium; Serotonin; Raphe Nuclei; Brain Stem; Appetite Regulation
PubMed: 37525500
DOI: 10.1111/jne.13328 -
Veterinary Research Communications Sep 2023Animals can sense their changing internal needs and then generate specific physiological and behavioural responses in order to restore homeostasis. Water-saline... (Review)
Review
Animals can sense their changing internal needs and then generate specific physiological and behavioural responses in order to restore homeostasis. Water-saline homeostasis derives from balances of water and sodium intake and output (drinking and diuresis, salt appetite and natriuresis), maintaining an appropriate composition and volume of extracellular fluid. Thirst is the sensation which drives to seek and consume water, regulated in the central nervous system by both neural and chemical signals. Water and electrolyte homeostasis depends on finely tuned physiological mechanisms, mainly susceptible to plasma Na concentration and osmotic pressure, but also to blood volume and arterial pressure. Increases of osmotic pressure as slight as 1-2% are enough to induce thirst ("homeostatic" or cellular), by activation of specialized osmoreceptors in the circumventricular organs, outside the blood-brain barrier. Presystemic anticipatory signals (by oropharyngeal or gastrointestinal receptors) inhibit thirst when fluids are ingested, or stimulate thirst associated with food intake. Hypovolemia, arterial hypotension, Angiotensin II stimulate thirst ("hypovolemic thirst", "extracellular dehydration"). Hypervolemia, hypertension, Atrial Natriuretic Peptide inhibit thirst. Circadian rhythms of thirst are also detectable, driven by suprachiasmatic nucleus in the hypothalamus. Such homeostasis and other fundamental physiological functions (cardiocircolatory, thermoregulation, food intake) are highly interdependent.
Topics: Animals; Thirst; Appetite; Mammals; Water
PubMed: 36932281
DOI: 10.1007/s11259-023-10104-2 -
Nature Communications Oct 2023Norepinephrine (NE) is a well-known appetite regulator, and the nor/adrenergic system is targeted by several anti-obesity drugs. To better understand the circuitry...
Norepinephrine (NE) is a well-known appetite regulator, and the nor/adrenergic system is targeted by several anti-obesity drugs. To better understand the circuitry underlying adrenergic appetite control, here we investigated the paraventricular hypothalamic nucleus (PVN), a key brain region that integrates energy signals and receives dense nor/adrenergic input, using a mouse model. We found that PVN NE level increases with signals of energy deficit and decreases with food access. This pattern is recapitulated by the innervating catecholaminergic axon terminals originating from NTS-neurons. Optogenetic activation of rostral-NTS → PVN projection elicited strong motivation to eat comparable to overnight fasting whereas its inhibition attenuated both fasting-induced & hypoglycemic feeding. We found that NTS-axons functionally targeted PVN-neurons by predominantly inhibiting them, in part, through α1-AR mediated potentiation of GABA release from ARC presynaptic terminals. Furthermore, glucoprivation suppressed PVN activity, which was required for hypoglycemic feeding response. These results define an ascending nor/adrenergic circuit, NTS → PVN, that conveys peripheral hunger signals to melanocortin pathway.
Topics: Hunger; Melanocortins; Adrenergic Agents; Appetite; Paraventricular Hypothalamic Nucleus; Norepinephrine; Hypoglycemic Agents
PubMed: 37857606
DOI: 10.1038/s41467-023-42362-8 -
JAMA Oncology Mar 2024Currently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Currently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context.
OBJECTIVES
To assess the effect of mirtazapine on appetite and energy consumption in patients with advanced non-small cell lung cancer (NSCLC).
DESIGN, SETTING, AND PARTICIPANTS
This randomized, double-blind, placebo-controlled clinical trial including adults was performed in a tertiary cancer care center from August 2018 to May 2022 with a follow-up of 8 weeks. Overall, 134 patients were screened; 114 were assessed for eligibility and 28 were excluded.
INTERVENTIONS
Patients were randomized in a 1:1 ratio to receive mirtazapine, 15 mg, or placebo for 2 weeks followed by a dose escalation to 30 mg until week 8 or placebo. Both groups received nutritional assessment and dietary advice.
MAIN OUTCOMES AND MEASURES
Appetite was assessed by the Anorexia Cachexia Scale and energy intake. Dietary parameters were evaluated at baseline, 4 weeks, and 8 weeks, with a 24-hour dietary recall, and energy quantification based on the Mexican system of nutritional equivalents.
RESULTS
A total of 86 patients met the inclusion criteria and were randomized to the placebo (n = 43) or the mirtazapine group (n = 43). The mean (SD) age was 63.5 (11.2) years, 41 were women (57.7%) and had adenocarcinoma, Eastern Cooperative Oncology Group performance status scale score of 1, stage IV NSCLC, and were receiving first-line treatment. Baseline characteristics were similar between groups. There was no difference in appetite scores in patients who received mirtazapine or placebo after 4 and 8 weeks. After 4 weeks, mirtazapine significantly increased energy intake (379.3 kcal; 95% CI, 1382.6-576.1; P < .001) including proteins (22.5 g; 95% CI, 11.5-33.4; P = .001), carbohydrates (43.4 g; 95% CI, 13.1-73.8; P = .006), and fats (13.2 g; 95% CI, 6.0-20.4; P = .006). Fats intake was significantly higher in patients in the mirtazapine group (14.5 g vs 0.7 g; P = .02) after 8 weeks. The mirtazapine group significantly decreased the proportion of patients with sarcopenia (82.8% vs 57.1%, P = .03) at 8 weeks. Patients on mirtazapine tolerated the treatment well, but reported a higher perception of nightmares at 2 weeks based on a 10 cm VAS score (0 [25th-75th percentile, 0-1] vs 0 [25th-75th percentile, 0-0] in the control group; P = .009) but this finding was nonsignificant after 4 and 8 weeks.
CONCLUSION AND RELEVANCE
In this randomized clinical trial of patients with advanced NSCLC, there was no difference in appetite scores in all patients who received mirtazapine or placebo, but the mirtazapine group had a significant increase in energy intake through the 4- and 8-week follow-up, mainly in fat intake, which is a better and crucial source of energy. The addition of mirtazapine in the treatment of patients with advanced NSCLC and anorexia may help these patients achieve their energy requirements and improve health-related quality of life, specifically emotional and cognitive functioning.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04748523.
Topics: Aged; Female; Humans; Male; Middle Aged; Anorexia; Appetite Stimulants; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Lung Neoplasms; Mirtazapine; Quality of Life; Adult
PubMed: 38206631
DOI: 10.1001/jamaoncol.2023.5232 -
Nutrients Aug 2023With the increasing prevalence of energy metabolism disorders such as diabetes, cardiovascular disease, obesity, and anorexia, the regulation of feeding has become the... (Review)
Review
With the increasing prevalence of energy metabolism disorders such as diabetes, cardiovascular disease, obesity, and anorexia, the regulation of feeding has become the focus of global attention. The gastrointestinal tract is not only the site of food digestion and absorption but also contains a variety of appetite-regulating signals such as gut-brain peptides, short-chain fatty acids (SCFAs), bile acids (BAs), bacterial proteins, and cellular components produced by gut microbes. While the central nervous system (CNS), as the core of appetite regulation, can receive and integrate these appetite signals and send instructions to downstream effector organs to promote or inhibit the body's feeding behaviour. This review will focus on the gut-brain axis mechanism of feeding behaviour, discussing how the peripheral appetite signal is sensed by the CNS via the gut-brain axis and the role of the central "first order neural nuclei" in the process of appetite regulation. Here, elucidation of the gut-brain axis mechanism of feeding regulation may provide new strategies for future production practises and the treatment of diseases such as anorexia and obesity.
Topics: Humans; Anorexia; Brain-Gut Axis; Appetite; Obesity; Eating
PubMed: 37686760
DOI: 10.3390/nu15173728 -
Current Organic Synthesis 2024In recent years, a growing global concern has been obesity. Patients with obesity are at major risk for developing a number of diseases. These diseases may significantly... (Review)
Review
In recent years, a growing global concern has been obesity. Patients with obesity are at major risk for developing a number of diseases. These diseases may significantly impact patient's daily lives and increase the mortality rate. Over a year, medication for obesity has undergone substantial changes. An amphetamine-like prescription drug called Phentermine (Adipex-P, Lomaira) is used to suppress appetite. In the last few years, Phentermine and its derivatives have attracted much attention due to their use in weight reduction; by reducing appetite or prolonging the feeling of fullness, it can aid in weight reduction. So, reviewing the synthesis of Phentermine and its derivatives becomes imperative. Therefore, various synthetic routes for Phentermine (from benzaldehyde, isopropyl phenyl ketone, dimethyl benzyl carbinol) and its derivatives synthesis, involving ortho-palladation, are also reviewed here comprehensively.
Topics: Phentermine; Humans; Appetite Depressants
PubMed: 37259208
DOI: 10.2174/1570179420666230530095245 -
Neuroscience and Biobehavioral Reviews May 2024Neuroscience offers important insights into the pathogenesis and treatment of obesity by investigating neural circuits underpinning appetite and feeding.... (Review)
Review
Neuroscience offers important insights into the pathogenesis and treatment of obesity by investigating neural circuits underpinning appetite and feeding. Gamma-aminobutyric acid (GABA), one of the most abundant neurotransmitters in the brain, and its associated receptors represent an array of pharmacologically targetable mediators of appetite signalling. Targeting the GABAergic system is therefore an increasingly investigated approach to obesity treatment. However, the many GABAergic projections that control feeding have yet to be collectively analysed. This review provides a comprehensive analysis of the relationship between GABAergic signalling and appetite by examining both foundational studies and the results of newly emerging chemogenetic/optogenetic experiments. A current snapshot of these efforts to map GABAergic projections influencing appetite is provided, and potential avenues for further investigation are provided.
PubMed: 38821151
DOI: 10.1016/j.neubiorev.2024.105743