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Analytical Methods : Advancing Methods... Jun 2024Methyl parathion, a highly toxic, efficient, and persistent organophosphorus pesticide, is widely used in China. Sibutramine, a non-amphetamine central nervous system...
Methyl parathion, a highly toxic, efficient, and persistent organophosphorus pesticide, is widely used in China. Sibutramine, a non-amphetamine central nervous system depressant, helps lose weight by disrupting hormone regulation, stimulating sympathetic nerves, and suppressing appetite. However, some unethical businesses fail to properly handle raw materials in foods like apple cider vinegar, leading to residual methyl parathion in apples or illegal excessive addition of sibutramine. Therefore, it is imperative to develop an immunoassay for the rapid detection of methyl parathion and sibutramine. The corresponding two haptens were prepared and coupled with the carrier proteins according to methyl parathion-sulfur-bovine serum protein (BSA)/chicken ovalbumin (OVA)-sibutramine (20 : 1 : excess, 15 : 1 : excess, 10 : 1 : excess, and 5 : 1 : excess), and sibutramine-BSA/OVA-methyl parathion (20 : 1 : excess, 10 : 1 : excess: 5 : 1 : excess, and 0 : 1 : excess). The result shows that the inhibition rate of the antibody obtained by methyl parathion-BSA/OVA-sibutramine (20 : 1 : excess) was higher than that of sibutramine-BSA/OVA-methyl parathion, which was 67.93%, and the concentration of methyl parathion was 8.65 ng mL at this inhibition rate. Thus, methyl parathion-BSA/OVA-sibutramine (8.65 : 1 : excess) and the corresponding antibodies were selected for subsequent method establishment. By changing the concentration of the coating and antibody, the inhibition rate was found when the coating was 0.125 ng mL and the antibody was diluted 4000 times. The antibody was used to develop a standard curve for the detection of sibutramine at the half-maximum inhibitory concentration (IC) is 4.59 ng mL, the limit of detection (IC) is 2.21 ng mL, the detection range is 2.89 to 7.28 ng mL, methyl p-phosphorus at the half-maximum inhibitory concentration (IC) is 15.34 ng mL, the limit of detection (IC) is 0.42 ng mL, the detection range is ng mL. Under these conditions, the recovery rate was between 88% and 102%, within reasonable limits, indicating the successful establishment of a rapid enzyme-linked ELISA assay.
Topics: Cyclobutanes; Enzyme-Linked Immunosorbent Assay; Malus; Methyl Parathion; Acetic Acid; Appetite Depressants; Food Contamination; Animals; Limit of Detection
PubMed: 38873980
DOI: 10.1039/d4ay00879k -
Journal of Pharmacy & Pharmaceutical... 2024Childhood obesity has emerged as a major global health issue, contributing to the increased prevalence of chronic conditions and adversely affecting the quality of life... (Review)
Review
Childhood obesity has emerged as a major global health issue, contributing to the increased prevalence of chronic conditions and adversely affecting the quality of life and future prospects of affected individuals, thereby presenting a substantial societal challenge. This complex condition, influenced by the interplay of genetic predispositions and environmental factors, is characterized by excessive energy intake due to uncontrolled appetite regulation and a Westernized diet. Managing obesity in childhood requires specific considerations compared with adulthood, given the vulnerability of the critical juvenile-adolescent period to toxicity and developmental defects. Consequently, common treatment options for adult obesity may not directly apply to younger populations. Therefore, research on childhood obesity has focused on genetic defects in regulating energy intake, alongside pharmacotherapy and dietary interventions as management approaches, with an emphasis on safety concerns. This review aims to summarize canonical knowledge and recent findings on genetic factors contributing to childhood obesity. Additionally, it assesses the efficacy and safety of existing pharmacotherapies and dietary interventions and suggests future research directions. By providing a comprehensive understanding of the complex dynamics of childhood obesity, this review aims to offer insights into more targeted and effective strategies for addressing this condition, including personalized healthcare solutions.
Topics: Humans; Pediatric Obesity; Child; Anti-Obesity Agents; Diet
PubMed: 38863827
DOI: 10.3389/jpps.2024.12861 -
Methods in Molecular Biology (Clifton,... 2024Automated patch clamp recording is a valuable technique in drug discovery and the study of ion channels. It allows for the precise measurement and manipulation of...
Automated patch clamp recording is a valuable technique in drug discovery and the study of ion channels. It allows for the precise measurement and manipulation of channel currents, providing insights into their function and modulation by drugs or other compounds. The melanocortin 4 receptor (MC4-R) is a G protein-coupled receptor (GPCR) crucial to appetite regulation, energy balance, and body weight. MC4-R signaling is complex and involves interactions with other receptors and neuropeptides in the appetite-regulating circuitry. MC4-Rs, like other GPCRs, are known to modulate ion channels such as Kir7.1, an inward rectifier potassium channel, in response to ligand binding. This modulation is critical for controlling ion flow across the cell membrane, which can influence membrane potential, excitability, and neurotransmission. The MC4-R is the target for the anti-obesity drug Imcivree. However, this drug is known to lack optimal potency and also has side effects. Using high-throughput techniques for studying the MC4-R/Kir7.1 complex allows researchers to rapidly screen many compounds or conditions, aiding the development of drugs that target this system. Additionally, automated patch clamp recording of this receptor-channel complex and its ligands can provide valuable functional and pharmacological insights supporting the development of novel therapeutic strategies. This approach can be generalized to other GPCR-gated ion channel functional complexes, potentially accelerating the pace of research in different fields with the promise to uncover previously unknown aspects of receptor-ion channel interactions.
Topics: Patch-Clamp Techniques; Animals; Humans; Receptor, Melanocortin, Type 4; Potassium Channels, Inwardly Rectifying; Ion Channel Gating; Receptors, G-Protein-Coupled; HEK293 Cells
PubMed: 38856905
DOI: 10.1007/978-1-0716-3818-7_14 -
Nutrition Research (New York, N.Y.) May 2024Gut peptides play a role in signaling appetite control in the hypothalamus. Limited knowledge exists regarding the release of these peptides in individuals with obesity... (Review)
Review
Gut peptides play a role in signaling appetite control in the hypothalamus. Limited knowledge exists regarding the release of these peptides in individuals with obesity before and during external stimuli. We hypothesize that the expression of gut peptides is different in the fasting and postprandial states in the scenario of obesity. PubMed/MEDLINE, Scopus, and Science Direct electronic databases were searched. The meta-analysis was performed using Review Manager Software. Randomized controlled trials that measured gut peptides in both obese and lean subjects were included in the analysis. A total of 552 subjects with obesity were enrolled in 25 trials. The gut peptide profile did not show any significant difference between obese and lean subjects for glucagon-like peptide 1 (95% confidence interval [CI], -1.21 to 0.38; P = .30), peptide YY (95% CI, -1.47 to 0.18; P = .13), and cholecystokinin (95% CI, -1.25 to 1.28; P = .98). Gut peptides are decreased by an increased high-fat, high-carbohydrate diet and by decreased chewing. There is no statistically significant difference in gut peptides between individuals with obesity and leanness in a fasting state. However, the release of gut peptides is affected in individuals with obesity following external stimuli, such as dietary interventions and chewing. Further studies are necessary to investigate the relationship between various stimuli and the release of gut peptides, as well as their impact on appetite regulation in subjects with obesity.
PubMed: 38843565
DOI: 10.1016/j.nutres.2024.04.007 -
Peptides Jun 2024The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions...
The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions such as skin pigmentation, sexual function and development, and inflammation. A growing body of both clinical and pre-clinical research is demonstrating the relevance of this system in metabolic health. Disruption of hypothalamic melanocortin signalling is the most common cause of monogenic obesity in humans. Setmelanotide, an FDA-approved analogue of alpha-melanocyte stimulating hormone (α-MSH) that functions by restoring central melanocortin signalling, has proven to be a potent pharmacological tool in the treatment of syndromic obesity. As the first effective therapy targeting the melanocortin system to treat metabolic disorders, its approval has sparked research to further harness the links between these melanocortin receptors and metabolic processes. Here, we outline the structure of the central and peripheral melanocortin system, discuss its critical role in the regulation of food intake, and review promising targets that may hold potential to treat metabolic disorders in humans.
PubMed: 38834138
DOI: 10.1016/j.peptides.2024.171255 -
Harmful Algae May 2024Cyanobacterial harmful algal blooms (cHABs) are pervasive sources of stress resulting in neurotoxicity in fish. A member of the widely distributed Microcystis genus of...
Cyanobacterial harmful algal blooms (cHABs) are pervasive sources of stress resulting in neurotoxicity in fish. A member of the widely distributed Microcystis genus of bloom-forming cyanobacteria, Microcystis wesenbergii can be found in many freshwater lakes, including Dianchi Lake (China), where it has become one of the dominant contributors to the lake's recurrent blooms. However, unlike its more well-known counterpart M. aeruginosa, the effects of dense non-microcystin-containing M. wesenbergii blooms are seldom studied. The disturbance of appetite regulation and feeding behaviour can have downstream effects on the growth of teleost fish, posing a significant challenge to aquaculture and conservation efforts. Here we examined the effects of M. wesenbergii blooms on the food intake of Acrossocheilus yunnanensis, a native cyprinid in southern China. This fish species has disappeared in Dianchi Lake, and its reintroduction might be negatively affected by the presence of this newly-dominant Microcystis species. We co-cultured juvenile A. yunnanensis with a non-microcystin-producing strain of M. wesenbergii at initial densities between 5 × 10 and 1 × 10 cells/mL and monitored fish feeding behaviour and changes in neurotransmitter and hormone protein levels. High-density M. wesenbergii cultures increased the feeding rate of co-cultured fish, elevating concentrations of appetite-stimulating signalling molecules (Agouti-related protein and γ-aminobutyric acid), while decreasing inhibitory ones (POMC). These changes coincided with histopathological alterations and reduced somatic indices in brain and intestinal tissues. Given this potential for detrimental effects and dysregulation of food intake, further studies are necessary to determine the impacts of chronic exposure of M. wesenbergii in wild fish.
Topics: Animals; Microcystis; Harmful Algal Bloom; Appetite Regulation; Cyprinidae; Eating; Microcystins; Lakes; China; Feeding Behavior
PubMed: 38830717
DOI: 10.1016/j.hal.2024.102647 -
Research Square May 2024Satiation is the physiologic process that regulates meal size and termination, and it is quantified by the calories consumed to reach satiation. Given its role in energy...
Satiation is the physiologic process that regulates meal size and termination, and it is quantified by the calories consumed to reach satiation. Given its role in energy intake, changes in satiation contribute to obesity's pathogenesis. Our study employed a protocolized approach to study the components of food intake regulation including a standardized breakfast, a gastric emptying study, appetite sensation testing, and a satiation measurement by an test. These studies revealed that satiation is highly variable among individuals, and while baseline characteristics, anthropometrics, body composition and hormones, contribute to this variability, these factors do not fully account for it. To address this gap, we explored the role of a germline polygenic risk score, which demonstrated a robust association with satiation. Furthermore, we developed a machine-learning-assisted gene risk score to predict satiation and leveraged this prediction to anticipate responses to anti-obesity medications. Our findings underscore the significance of satiation, its inherent variability, and the potential of a genetic risk score to forecast it, ultimately allowing us to predict responses to different anti-obesity interventions.
PubMed: 38826309
DOI: 10.21203/rs.3.rs-4402499/v1 -
Journal of Internal Medicine Jun 2024The hypothalamic-pituitary-adrenal axis is an extremely dynamic system with a combination of both circadian and ultradian oscillations. This state of 'continuous dynamic... (Review)
Review
The hypothalamic-pituitary-adrenal axis is an extremely dynamic system with a combination of both circadian and ultradian oscillations. This state of 'continuous dynamic equilibration' provides a platform that is able to anticipate events, is sensitive in its response to stressors, remains robust during perturbations of both the internal and external environments and shows plasticity to adapt to a changed environment. In this review, we describe these oscillations of glucocorticoid (GC) hormones and why they are so important for GC-dependent gene activation in the brain and liver, and their consequent effects on the regulation of synaptic and memory function as well as appetite control and metabolic regulation. Abnormalities of mood, appetite and metabolic regulation are well-known consequences of GC therapy, and we suggest that the pattern of GC treatment and hormone replacement should be a much higher priority for endocrinologists and the pharmaceutical industry. One of the major impediments to our research on the importance of these cortisol rhythms in our patients has been our inability to measure repeated levels of hormones across the day in patients in their home or work surroundings. We describe how new wearable methodologies now allow the measurement of 24-h cortisol profiles - including during sleep - and will enable us to define physiological normality and allow us both to develop better diagnostic tests and inform, at an individual patient level, how to improve replacement therapy.
PubMed: 38825772
DOI: 10.1111/joim.13795 -
Peptides May 2024The approval of the glucagon-like peptide 1 (GLP-1) mimetics semaglutide and liraglutide for management of obesity, independent of type 2 diabetes (T2DM), has initiated...
The approval of the glucagon-like peptide 1 (GLP-1) mimetics semaglutide and liraglutide for management of obesity, independent of type 2 diabetes (T2DM), has initiated a resurgence of interest in gut-hormone derived peptide therapies for the management of metabolic diseases, but side-effect profile is a concern for these medicines. However, the recent approval of tirzepatide for obesity and T2DM, a glucose-dependent insulinotropic polypeptide (GIP), GLP-1 receptor co-agonist peptide therapy, may provide a somewhat more tolerable option. Despite this, an increasing number of non-incretin alternative peptides are in development for obesity, and it stands to reason that other hormones will take to the limelight in the coming years, such as peptides from the neuropeptide Y family. This narrative review outlines the therapeutic promise of the neuropeptide Y family of peptides, comprising of the 36 amino acid polypeptides neuropeptide Y (NPY), peptide tyrosine-tyrosine (PYY) and pancreatic polypeptide (PP), as well as their derivatives. This family of peptides exerts a number of metabolically relevant effects such as appetite regulation and can influence pancreatic beta-cell survival. Although some of these actions still require full translation to the human setting, potential therapeutic application in obesity and type 2 diabetes is conceivable. However, like GLP-1 and GIP, the endogenous NPY, PYY and PP peptide forms are subject to rapid in vivo degradation and inactivation by the serine peptidase, dipeptidyl-peptidase 4 (DPP-4), and hence require structural modification to prolong circulating half-life. Numerous protective modification strategies are discussed in this regard herein, alongside related impact on biological activity profile and therapeutic promise.
PubMed: 38825012
DOI: 10.1016/j.peptides.2024.171256 -
Scientific Reports May 2024Marine mammals possess a specific subcutaneous fat layer called blubber that not only insulates and stores energy but also secretes bioactive substances. However, our...
Marine mammals possess a specific subcutaneous fat layer called blubber that not only insulates and stores energy but also secretes bioactive substances. However, our understanding of its role as a secretory organ in cetaceans is incomplete. To exhaustively explore the hormone-like substances produced in dolphin subcutaneous adipose tissue, we performed seasonal blubber biopsies from captive female common bottlenose dolphins (Tursiops truncatus; N = 8, n = 32) and analyzed gene expression via transcriptomics. Analysis of 186 hormone-like substances revealed the expression of 58 substances involved in regulating energy metabolism, tissue growth/differentiation, vascular regulation, immunity, and ion/mineral homeostasis. Adiponectin was the most abundantly expressed gene, followed by angiopoietin protein like 4 and insulin-like growth factor 2. To investigate the endocrine/secretory responses of subcutaneous adipose tissue to the surrounding temperature, we subsequently compared the mean expression levels of the genes during the colder and warmer seasons. In the colder season, molecules associated with appetite suppression, vasodilation, and tissue proliferation were relatively highly expressed. In contrast, warmer seasons enhanced the expression of substances involved in tissue remodeling, immunity, metabolism, and vasoconstriction. These findings suggest that dolphin blubber may function as an active secretory organ involved in the regulation of metabolism, appetite, and tissue reorganization in response to changes in the surrounding environment, providing a basis for elucidating the function of hormone-like substances in group-specific evolved subcutaneous adipose tissue.
Topics: Animals; Bottle-Nosed Dolphin; Subcutaneous Fat; Female; Transcriptome; Gene Expression Profiling; Hormones; Seasons; Energy Metabolism
PubMed: 38822022
DOI: 10.1038/s41598-024-63018-7