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Neuropharmacology Sep 2024Diets high in sucrose and fat are becoming more prevalent the world over, accompanied by a raised prevalence of cardiovascular diseases, cancers, diabetes, obesity, and...
Diets high in sucrose and fat are becoming more prevalent the world over, accompanied by a raised prevalence of cardiovascular diseases, cancers, diabetes, obesity, and metabolic syndrome. Clinical studies link unhealthy diets with the development of mental health disorders, particularly depression. Here, we investigate the effects of 12 days of sucrose consumption administered as 2 L of 25% sucrose solution daily for 12 days in Göttingen minipigs on the function of brain receptors involved in reward and motivation, regulating feeding, and pre- and post-synaptic mechanisms. Through quantitative autoradiography of cryostat sections containing limbic brain regions, we investigated the effects of sucrose restricted to a 1-h period each morning, on the specific binding of [H]raclopride on dopamine D2/3 receptors, [H]UCB-J at synaptic vesicle glycoprotein 2A (SV2A), [H]MPEPγ at metabotropic glutamate receptor subtype 5 (mGluR5) and [H]SR141716A at the cannabinoid receptor 1 (CB1). Compared to control diet animals, the sucrose group showed significantly lower [H]UCB-J and [H]MPEPγ binding in the prefrontal cortex. The sucrose-consuming minipigs showed higher hippocampal CB1 binding, but unaltered dopamine D2/3 binding compared to the control group. We found that the sucrose diet reduced the synaptic density marker while increasing CB1 binding in limbic brain structures, which may subserve maladaptive changes in appetite regulation and feeding. Further studies of the effects of diets and lifestyle habits on brain neuroreceptor and synaptic density markers are warranted.
Topics: Animals; Swine, Miniature; Swine; Sucrose; Male; Receptor, Metabotropic Glutamate 5; Receptors, Cannabinoid; Synapses; Receptor, Cannabinoid, CB1; Receptors, Dopamine D2; Brain; Female; Receptors, Dopamine D3
PubMed: 38810925
DOI: 10.1016/j.neuropharm.2024.110018 -
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 -
Physiological Genomics May 2024Commercial culture of channel catfish () occurs in earthen ponds that are characterized by diel swings in dissolved oxygen concentration that can fall to severe levels...
Commercial culture of channel catfish () occurs in earthen ponds that are characterized by diel swings in dissolved oxygen concentration that can fall to severe levels of hypoxia which can suppress appetite and lead to suboptimal growth. Given the significance of the hypothalamus in regulating these processes in other fishes, an investigation into the hypothalamus transcriptome was conducted to identify specific genes and expression patterns responding to hypoxia. Channel catfish in normoxic water were compared to catfish subjected to 12 hours of hypoxia (20% oxygen saturation; 1.8 mg O/L; 27 °C) followed by 12 hours of recovery in normoxia to mimic 24-hours in a catfish aquaculture pond. Fish were sampled at 0-, 6-, 12-, 18-, and 24-hour time points, with the 6- and 12-hour samplings occurring during hypoxia. A total of 190 genes were differentially expressed during the experiment, with most occurring during hypoxia and returning to baseline values within 6 hours of normoxia. Differentially expressed genes were sorted by function into Gene Ontology biological processes and revealed that most were categorized as "response to hypoxia", "sprouting angiogenesis", and "cellular response to xenobiotic stimulus". The patterns of gene expression reported here suggest that transcriptome responses to hypoxia are broad and quickly reversibly with the onset of normoxia. Although no genes commonly reported to modulate appetite were found to be differentially expressed in this experiment, several candidates were identified for future studies investigating the interplay between hypoxia and appetite in channel catfish, including , , , and .
PubMed: 38808773
DOI: 10.1152/physiolgenomics.00007.2024 -
Appetite May 2024Food insecurity - defined as having limited access to nutritious foods - is linked with obesity. Previous research has also shown that food insecurity is associated with...
Food insecurity - defined as having limited access to nutritious foods - is linked with obesity. Previous research has also shown that food insecurity is associated with lower levels of leisure-time physical activity (physical activity performed outside of essential activities). This association may occur in part due to concerns about preserving levels of energy during times of food shortage. Currently, no scale exists which measures this construct. Therefore, we aimed to develop and validate such a scale - the food insecurity physical activity concerns scale (FIPACS). Participants (N = 603, individuals with food insecurity = 108) completed an online survey, consisting of the FIPACS, the International Physical Activity Questionnaire short-form (IPAQ), the restraint subscale of the Dutch Eating Behaviour Questionnaire (DEBQ), the amotivation subscale of the Behaviour Regulation In Exercise Questionnaire-2 (BREQ-2), and the Behavioural Inhibition System/Behavioural Approach System Reactivity scale (BIS/BAS) to assess convergent and divergent validity. An exploratory factor analysis revealed a four-factor model of the FIPACS - namely 'Concerns relating to hunger', 'Concerns of replenishment and calories', 'Concerns of physiological effects of exercise' and 'Compensatory behaviours' which was verified through a confirmatory factor analysis. To assess test-retest reliability, 100 participants completed the FIPACS again two weeks later. The FIPACS had good internal, test-retest reliability and divergent validity. However, there was limited evidence of convergent validity. Future studies could incorporate this scale when investigating the association between food insecurity and physical activity.
PubMed: 38801996
DOI: 10.1016/j.appet.2024.107516 -
Appetite May 2024Terminating a meal after achieving satiation is a critical step in maintaining a healthy energy balance. Despite the extensive collection of information over the last... (Review)
Review
Terminating a meal after achieving satiation is a critical step in maintaining a healthy energy balance. Despite the extensive collection of information over the last few decades regarding the neural mechanisms controlling overall eating, the mechanism underlying different temporal phases of eating behaviors, especially satiation, remains incompletely understood and is typically embedded in studies that measure the total amount of food intake. In this review, we summarize the neural circuits that detect and integrate satiation signals to suppress appetite, from interoceptive sensory inputs to the final motor outputs. Due to the well-established role of cholecystokinin (CCK) in regulating the satiation, we focus on the neural circuits that are involved in regulating the satiation effect caused by CCK. We also discuss several general principles of how these neural circuits control satiation, as well as the limitations of our current understanding of the circuits function. With the application of new techniques involving sophisticated cell-type-specific manipulation and mapping, as well as real-time recordings, it is now possible to gain a better understanding of the mechanisms specifically underlying satiation.
PubMed: 38801994
DOI: 10.1016/j.appet.2024.107512 -
Nutrients May 2024Unhealthy lifestyles (high-fat diet, smoking, alcohol consumption, too little exercise, etc.) in the current society are prone to cause lipid metabolism disorders... (Review)
Review
Unhealthy lifestyles (high-fat diet, smoking, alcohol consumption, too little exercise, etc.) in the current society are prone to cause lipid metabolism disorders affecting the health of the organism and inducing the occurrence of diseases. Saponins, as biologically active substances present in plants, have lipid-lowering, inflammation-reducing, and anti-atherosclerotic effects. Saponins are thought to be involved in the regulation of lipid metabolism in the body; it suppresses the appetite and, thus, reduces energy intake by modulating pro-opiomelanocortin/Cocaine amphetamine regulated transcript (POMC/CART) neurons and neuropeptide Y/agouti-related peptide (NPY/AGRP) neurons in the hypothalamus, the appetite control center. Saponins directly activate the AMP-activated protein kinase (AMPK) signaling pathway and related transcriptional regulators such as peroxisome-proliferator-activated-receptors (PPAR), CCAAT/enhancer-binding proteins (C/EBP), and sterol-regulatory element binding proteins (SREBP) increase fatty acid oxidation and inhibit lipid synthesis. It also modulates gut-liver interactions to improve lipid metabolism by regulating gut microbes and their metabolites and derivatives-short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine (TMA), lipopolysaccharide (LPS), et al. This paper reviews the positive effects of different saponins on lipid metabolism disorders, suggesting that the gut-liver axis plays a crucial role in improving lipid metabolism processes and may be used as a therapeutic target to provide new strategies for treating lipid metabolism disorders.
Topics: Saponins; Lipid Metabolism; Humans; Liver; Gastrointestinal Microbiome; Animals; Signal Transduction; Gastrointestinal Tract
PubMed: 38794751
DOI: 10.3390/nu16101514 -
Nature Metabolism Jun 2024Nutrient handling is an essential function of the gastrointestinal tract. Hormonal responses of small intestinal enteroendocrine cells (EECs) have been extensively...
Nutrient handling is an essential function of the gastrointestinal tract. Hormonal responses of small intestinal enteroendocrine cells (EECs) have been extensively studied but much less is known about the role of colonic EECs in metabolic regulation. To address this core question, we investigated a mouse model deficient in colonic EECs. Here we show that colonic EEC deficiency leads to hyperphagia and obesity. Furthermore, colonic EEC deficiency results in altered microbiota composition and metabolism, which we found through antibiotic treatment, germ-free rederivation and transfer to germ-free recipients, to be both necessary and sufficient for the development of obesity. Moreover, studying stool and blood metabolomes, we show that differential glutamate production by intestinal microbiota corresponds to increased appetite and that colonic glutamate administration can directly increase food intake. These observations shed light on an unanticipated host-microbiota axis in the colon, part of a larger gut-brain axis, that regulates host metabolism and body weight.
Topics: Animals; Enteroendocrine Cells; Gastrointestinal Microbiome; Mice; Colon; Obesity; Mice, Inbred C57BL; Glutamic Acid; Brain-Gut Axis; Hyperphagia
PubMed: 38777856
DOI: 10.1038/s42255-024-01044-5 -
Poultry Science Jul 2024Adrenomedullin has various physiological roles including appetite regulation. The objective of present study was to determine the effects of ICV injection of...
Adrenomedullin has various physiological roles including appetite regulation. The objective of present study was to determine the effects of ICV injection of adrenomedullin and its interaction with NPY and CCK receptors on food intake regulation. In experiment 1, chickens received ICV injection of saline and adrenomedullin (1, 2, and 3 nmol). In experiment 2, birds injected with saline, B5063 (NPY receptor antagonist, 1.25 µg), adrenomedullin (3 nmol) and co-injection of B5063+adrenomedullin. Experiments 3 to 5 were similar to experiment 2 and only SF22 (NPY receptor antagonist, 1.25 µg), SML0891 (NPY receptor antagonist, 1.25 µg) and CCK (1 nmol) were injected instead of B5063. In experiment 6, ICV injection of saline and CCK (0.125, 0.25, and 0.5 nmol) were done. In experiment 7, chickens injected with saline, CCK (0.125 nmol), adrenomedullin (3 nmol) and co-injection of CCK+adrenomedullin. After ICV injection, birds were returned to their individual cages immediately and cumulative food intake was measured at 30, 60, and 120 min after injection. Adrenomedullin (2 and 3 nmol) decreased food intake compared to control group (P < 0.05). Coinjection of B5063+adrenomedullin amplified hypophagic effect of adrenomedullin (P < 0.05). The ICV injection of the CCK (0.25 and 0.5 nmol) reduced food intake (P < 0.05). Co-injection of the CCK+adrenomedullin significantly potentiated adrenomedullin-induced hypophagia (P < 0.05). Administration of the SF22, SML0891 and CCK had no effect on the anorexigenic response evoked by adrenomedullin (P > 0.05). These results suggested that the hypophagic effect of the adrenomedullin is mediated by NPY and CCK receptors. However, our novel results should form the basis for future experiments.
Topics: Animals; Adrenomedullin; Chickens; Injections, Intraventricular; Neuropeptide Y; Eating; Female; Avian Proteins; Appetite Regulation; Male; Receptors, Cholecystokinin; Cholecystokinin
PubMed: 38772088
DOI: 10.1016/j.psj.2024.103819 -
European Review For Medical and... May 2024The article "Metabolomic profiling of amino acid alterations in anorexia nervosa: implications for appetite regulation and therapeutic strategies", by K. Donato, K....
The article "Metabolomic profiling of amino acid alterations in anorexia nervosa: implications for appetite regulation and therapeutic strategies", by K. Donato, K. Dhuli, A. Macchia, M.C. Medori, C. Micheletti, G. Bonetti, M.R. Ceccarini, T. Beccari, P. Chiurazzi, S. Cristoni, V. Benfatti, L. Dalla Ragione, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 64-76-DOI: 10.26355/eurrev_202312_34691-PMID: 38112949 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: - Issues with ethical approval - Undeclared conflict of interest Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. The authors disagree with this retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34691.
Topics: Humans; Anorexia Nervosa; Metabolomics; Amino Acids; Appetite Regulation
PubMed: 38766780
DOI: 10.26355/eurrev_202405_36194 -
Scientific Reports May 2024The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite....
The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in the control of appetite. Based on the resting-state functional connectivity map of the hypothalamus, a 12-channel net-tDCS protocol was generated (Neuroelectrics Starstim system), which included anodal, cathodal and sham stimulation. Ten participants with overweight or obesity were enrolled in a sham-controlled, crossover study. During stimulation or sham control, participants completed a stop-signal task to measure inhibitory control. Overall, stimulation was well tolerated. Anodal net-tDCS resulted in faster stop signal reaction time (SSRT) compared to sham (p = 0.039) and cathodal net-tDCS (p = 0.042). Baseline functional connectivity of the target network correlated with SSRT after anodal compared to sham stimulation (p = 0.016). These preliminary data indicate that modulating hypothalamus functional network connectivity via net-tDCS may result in improved inhibitory control. Further studies need to evaluate the effects on eating behavior and metabolism.
Topics: Humans; Transcranial Direct Current Stimulation; Hypothalamus; Male; Adult; Female; Feasibility Studies; Obesity; Cross-Over Studies; Appetite; Middle Aged; Nerve Net; Appetite Regulation; Reaction Time
PubMed: 38762574
DOI: 10.1038/s41598-024-61852-3