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Biomedicine & Pharmacotherapy =... Jul 2024GDF15 is a stress response cytokine and a distant member of the transforming growth factor beta (TGFβ) superfamily, its levels increase in response to cell stress and... (Review)
Review
GDF15 is a stress response cytokine and a distant member of the transforming growth factor beta (TGFβ) superfamily, its levels increase in response to cell stress and certain diseases in the serum. To exert its effects, GDF15 binds to glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL), which was firstly identified in 2017 and highly expressed in the brain stem. Many studies have demonstrated that elevated serum GDF15 is associated with anorexia and weight loss. Herein, we focus on the biology of GDF15, specifically how this circulating protein regulates appetite and metabolism in influencing energy homeostasis through its actions on hindbrain neurons to shed light on its impact on diseases such as obesity and anorexia/cachexia syndromes. It works as an endocrine factor and transmits metabolic signals leading to weight reduction effects by directly reducing appetite and indirectly affecting food intake through complex mechanisms, which could be a promising target for the treatment of energy-intake disorders.
Topics: Humans; Growth Differentiation Factor 15; Animals; Metabolic Diseases; Energy Metabolism; Obesity; Anorexia; Appetite
PubMed: 38810400
DOI: 10.1016/j.biopha.2024.116809 -
Endocrinology Jan 2022Growth differentiation factor 15 (GDF15) has recently moved to the forefront of metabolism research. When administered pharmacologically, GDF15 reduces food intake and... (Review)
Review
Growth differentiation factor 15 (GDF15) has recently moved to the forefront of metabolism research. When administered pharmacologically, GDF15 reduces food intake and lowers body weight via the hindbrain-situated receptor GFRAL (glial cell-derived neurotrophic factor family receptor alpha-like). Endogenous GDF15 is a ubiquitous cellular stress signal that can be produced and secreted by a variety of cell types. Circulating levels are elevated in a series of disease states, but also in response to exogenous agents such as metformin, colchicine, AICAR, and cisplatin. Recently, exercise has emerged as a relevant intervention to interrogate GDF15 physiology. Prolonged endurance exercise increases circulating GDF15 to levels otherwise associated with certain pathological states and in response to metformin treatment. The jury is still out on whether GDF15 is a functional "exerkine" mediating organ-to-brain crosstalk or whether it is a coincidental bystander. In this review, we discuss the putative physiological implication of exercise-induced GDF15, focusing on the potential impact on appetite and metabolism.
Topics: Animals; Appetite; Eating; Exercise; Feeding Behavior; Growth Differentiation Factor 15; Humans; Muscle, Skeletal; Physical Conditioning, Animal; Signal Transduction
PubMed: 34849709
DOI: 10.1210/endocr/bqab242 -
Phytomedicine : International Journal... May 2023Food intake behavior is influenced by both physiological and psychological complex processes, such as appetite, satiety, and hunger. The neuroendocrine regulation of... (Review)
Review
BACKGROUND
Food intake behavior is influenced by both physiological and psychological complex processes, such as appetite, satiety, and hunger. The neuroendocrine regulation of food intake integrates short- and long-term acting signals that modulate the moment of intake and energy storage/expenditure, respectively. These signals are classified as orexigenic, those that activate anabolic pathways and the desire of eating, and anorexigenic, those that activate the catabolic pathways and a sensation of satiety. Appetite control by natural vegetal compounds is an intense area of research and new pharmacological interventions have been emerging based on an understanding of appetite regulation pathways. Several validated psychometric tools are used to assess the efficacy of these plant ingredients. However, these data are not conclusive if they are not complemented with physiological parameters, such as anthropometric evaluations (body weight and composition) and the analysis of hormones related to adipose tissue and appetite in blood.
PURPOSE
The purpose of this manuscript is the critical analysis of the plant compounds studied to date in the literature with potential for the neuroendocrine regulation of hunger in order to determine if the use of phytochemicals for the treatment of obesity constitutes an effective and/or promising therapeutic tool.
METHODS
Relevant information on neuroendocrine regulation of hunger and satiety for the treatment of obesity by plant compounds up to 2022 in English and/or Spanish were derived from online databases using the PubMed search engine and Google Scholar with relevant keywords and operators.
RESULTS
Accordingly, the comparison performed in this review between previous studies showed a high degree of experimental heterogeneity. Among the studies reviewed here, only a few of them establish comprehensively a potential correlation between the effect of the ingredient on hunger or satiety, body changes and a physiological response.
CONCLUSIONS
More systematic clinical studies are required in future research. The first approach should be to decode the pattern of circulating hormones regulating hunger, satiety, and appetite in overweight/obese subjects. Thereafter, studies should correlate brain connectivity at the level of the hypothalamus, gut and adipose tissue with the hormone patterns modulating appetite and satiety. Extracts whose mode of action have been well characterized and that are safe, can be used clinically to perform a moderate, but continuous, caloric restriction in overweight patients to lose weight excess into a controlled protocol.
Topics: Humans; Hunger; Overweight; Appetite; Obesity; Hormones; Energy Intake
PubMed: 36921427
DOI: 10.1016/j.phymed.2023.154735 -
Neuropharmacology Aug 2019To maintain sodium homeostasis, animals will readily seek and ingest salt when salt-depleted, even at concentrations that they typically find aversive when sodium... (Review)
Review
To maintain sodium homeostasis, animals will readily seek and ingest salt when salt-depleted, even at concentrations that they typically find aversive when sodium replete. This innate behaviour is known as sodium (or salt) appetite. Salt appetite is subserved by a conserved brain network that senses sodium need and promotes the ingestion of salty substances when sodium-deficient. The subfornical organ (SFO) is a circumventricular organ that has diverse roles encompassing cardiovascular regulation, energy balance, immune responses, reproduction, and hydromineral balance. The SFO acts as a central sensor of sodium need and is essential for the generation of salt appetite. In this review, we discuss recent findings on the neurochemical and circuit-level organisation of the SFO in the context of sodium appetite. This article is part of the Special Issue entitled 'Hypothalamic Control of Homeostasis'.
Topics: Animals; Appetite; Homeostasis; Humans; Sodium Chloride, Dietary; Subfornical Organ
PubMed: 30118727
DOI: 10.1016/j.neuropharm.2018.08.012 -
Appetite Dec 2020
Topics: Appetite; Bariatric Surgery; Humans; Obesity, Morbid
PubMed: 32750394
DOI: 10.1016/j.appet.2020.104810 -
International Journal of Environmental... Aug 2022Although appetite and its disorders have been implicated in disease progression and outcomes, ghrelin concentrations, an objective appetite measure, are rarely assessed...
Although appetite and its disorders have been implicated in disease progression and outcomes, ghrelin concentrations, an objective appetite measure, are rarely assessed in patients with gynecological malignancies. The present study aimed to assess changes in post-operative versus pre-operative appetite levels in patients with gynecological cancers scheduled for tumor removal surgery (N = 53). Acylated ghrelin concentrations were assessed as an objective appetite proxy, whereas the Council of Nutrition appetite questionnaire (CNAQ) was employed as a subjective appetite measure. Ghrelin concentrations were increased post-operatively (median: 12.1 pg/mL, IQR: 0.67 to 23.5, -value = 0.001) but the perceived appetite of patients (CNAQ) remained unchanged (median: -1, IQR: -3 to 1). Tumor removal surgery decreased all anthropometric indices (body weight, body mass index, waist and hips circumferences, triceps skinfolds, body fat, fat mass and fat mass index, -value ≤ 0.001 for all) and doubled the risk of malnutrition among patients. No difference was recorded in the change in participants' objective and subjective appetite when they were classified according to the tumor type. No correlation was observed between ghrelin concentrations and CNAQ score pre-operatively (Spearman's rho correlation coefficient = -0.181, -value = 0.298) or post-operatively (Spearman's rho correlation coefficient = 0.071, -value = 0.684). The observed post-operative rise in ghrelin concentrations is associated with body weight loss and consists of a possible defense mechanism of the human body, aiming to prolong survival.
Topics: Appetite; Ghrelin; Humans; Malnutrition; Neoplasms; Pilot Projects
PubMed: 36011958
DOI: 10.3390/ijerph191610322 -
The American Journal of Clinical... Jul 2023Obesity is increasing at an alarming rate. The effectiveness of currently available strategies for the treatment of obesity (including pharmacologic, surgical, and...
Obesity is increasing at an alarming rate. The effectiveness of currently available strategies for the treatment of obesity (including pharmacologic, surgical, and behavioral interventions) is limited. Understanding the neurobiology of appetite and the important drivers of energy intake (EI) can lead to the development of more effective strategies for the prevention and treatment of obesity. Appetite regulation is complex and is influenced by genetic, social, and environmental factors. It is intricately regulated by a complex interplay of endocrine, gastrointestinal, and neural systems. Hormonal and neural signals generated in response to the energy state of the organism and the quality of food eaten are communicated by paracrine, endocrine, and gastrointestinal signals to the nervous system. The central nervous system integrates homeostatic and hedonic signals to regulate appetite. Although there has been an enormous amount of research over many decades regarding the regulation of EI and body weight, research is only now yielding potentially effective treatment strategies for obesity. The purpose of this article is to summarize the key findings presented in June 2022 at the 23rd annual Harvard Nutrition Obesity Symposium entitled "The Neurobiology of Eating Behavior in Obesity: Mechanisms and Therapeutic Targets." Findings presented at the symposium, sponsored by NIH P30 Nutrition Obesity Research Center at Harvard, enhance our current understanding of appetite biology, including innovative techniques used to assess and systematically manipulate critical hedonic processes, which will shape future research and the development of therapeutics for obesity prevention and treatment.
Topics: Humans; Eating; Feeding Behavior; Obesity; Appetite; Body Weight
PubMed: 37149092
DOI: 10.1016/j.ajcnut.2023.05.003 -
MMW Fortschritte Der Medizin Aug 2020
Review
Topics: Aged; Appetite; Geriatric Assessment; Humans; Nutrition Assessment
PubMed: 32780379
DOI: 10.1007/s15006-020-0747-6 -
The Journal of Physiology Aug 2023An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory... (Randomized Controlled Trial)
Randomized Controlled Trial
An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, -48.8 pmol/L; exercise: -22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. KEY POINTS: Carbohydrate and exercise independently influence key appetite-regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon-like peptide 1 and succinate levels.
Topics: Male; Appetite; Appetite Regulation; Cross-Over Studies; Dietary Carbohydrates; Energy Intake; Exercise; Ghrelin; Glucagon-Like Peptide 1; Insulin; Peptide YY; Succinates; Humans
PubMed: 37269207
DOI: 10.1113/JP284294 -
Biomolecules Jul 2023Physical exercise is considered an important physiological intervention able to prevent cardiovascular diseases, obesity, and obesity-related cardiometabolic imbalance....
Physical exercise is considered an important physiological intervention able to prevent cardiovascular diseases, obesity, and obesity-related cardiometabolic imbalance. Nevertheless, basic molecular mechanisms that govern the metabolic benefits of physical exercise are poorly understood. Recent data unveil new mechanisms that potentially explain the link between exercise, feeding suppression, and obesity.
Topics: Humans; Appetite Regulation; Exercise; Cardiovascular Diseases; Obesity
PubMed: 37627235
DOI: 10.3390/biom13081170