Appetite Regulation Research Articles

The interplay between white adipose tissue, adipokines, and structural gray matter changes

AbstractThe growing global obesity issue emphasizes the importance of understanding its health implications. Previous research has identified consistent alterations in gray matter (GM) volume in connection with obesity. Given the various implications of distinct fat compartments and the potential role of adipose tissue‐derived adipokines in brain health, a more detailed investigation of adiposity is required. This study investigates a sample of 65 males with varying body mass indices to explore the relationship between various fat compartments, adipokine levels, and volumetric GM variations, aiming to provide a deeper understanding of the interplay between adiposity, brain structure, and metabolic signals. Whole‐body magnetic resonance imaging (MRI) was used to assess total, visceral, and subcutaneous adipose tissue, while MR spectroscopy was performed to capture liver fat content. For the assessment of adipokine levels leptin and adiponectin concentrations were measured, and structural brain images underwent cortical and subcortical segmentation for GM volume and thickness. A predictive modeling approach with leave‐one‐out cross‐validation was used to predict body composition metrics and adipokine levels based on structural GM data. Our investigation revealed diminished GM volume and thickness correlated with elevated leptin levels in areas crucial for appetite regulation, decision‐making, and cognitive control, including the anterior insula, orbitofrontal cortex, and anterior cingulate cortex. These findings suggest a potential adverse impact of heightened leptin concentrations on brain health and eating habits. Contrary to expectations, our investigation found no significant relationship between GM volume and any of the measured fat compartments. This result prompts the need for further research to elucidate the relationship between obesity, adipokines, and brain structure.

Semaglutide and health risk: Development and validation of a LC-HRMS method for testing semaglutide in whole blood and application to real cases

The use of semaglutide, also known by its trade name Ozempic®, has been increasing worldwide in recent years due to its benefits in treating type II diabetes. Thanks to its effects on appetite regulation, in many countries it is also used to treat obesity. However, due to its promotion by social media and celebrities as a weight-loss treatment, semaglutide is misused by a non-diabetic and non-obese population and by a young public, which is the main target of these media. Following the alert by the ANSM (Agence nationale de sécurité du médicament) in France and the FDA (Food and Drug Administration) in the United States, which imposed the addition of fatal effects to the list of side effects, the misuse of semaglutide seems to be becoming a public health problem. For this reason, it seems important that a toxicology laboratory has the capacity to test for semaglutide in blood.In this study, the authors have developed and validated a method for the identification and quantification of semaglutide in whole blood using a LC-HRMS.After the addition of the internal standard (bovine insulin), the blood was subjected to protein precipitation using a mix of acetonitrile/methanol (70:30,v:v). The validation procedure demonstrated an acceptable linearity between 2 and 500 ng/mL. LOD and LOQ were 1 and 2 ng/mL, respectively. Intra and inter-day precision were below 20 % at three concentrations. The method was successfully applied to the blood samples of 3 diabetic patients under treatment of semaglutide. The samples tested positive with concentrations ranging from 31 to 70 ng/mL which fall within the limits of therapeutic blood concentrations described in the literature.

Circadian and ultradian rhythms: Clinical implications.

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.

Effect of coffee intake on appetite parameters in woman with overweight or obesity: A pilot crossover randomized trial

IntroductionCoffee consumption has demonstrated an effect on the regulation of appetite, causing less hunger and/or greater satiety; however, its effects are not well known in woman with overweight or obesity. Therefore, this study aimed to evaluate the effect of coffee consumption on hunger, satiety, sensory specific desire (SSD), and dietary intake in women with overweight or obesity. MethodologyA randomized crossover clinical trial was realized in 3 sessions: in the first session a clinical history, anthropometric measurements and body composition analysis were performed; in sessions 2 and 3 the participants randomly consumed 240mL of coffee with 6mg/caffeine/kg of weight or 240mL of water along with a standardized breakfast. At fasting and every 30min after breakfast for the next 3h, appetite sensations and SSD were recorded using visual analog scales. Blood samples were taken at fasting, 30 and 180min after breakfast. Dietary intake was recorded in the rest of the intervention days. ResultsIn the coffee intervention there was an increased desire for sweet foods, higher fructose intake during the rest of the day, and higher triglyceride levels than with the water intervention. No differences were detected in ghrelin or cholecystokinin. ConclusionsCoffee consumption may lead to higher triglycerides and higher intake of simple sugars, mainly fructose, through changes in the SSD.Clinical Trial Registration: https://clinicaltrials.gov/NCT05774119.

Improved leptin sensitivity and increased soluble leptin receptor concentrations may underlie the additive effects of combining PYY(3–36) and exendin-4 on body weight lowering in diet-induced obese mice

ObjectiveCo-treatment with long acting PYY and the GLP-1 receptor agonists has potential as an efficient obesity treatment. This study investigates whether the mechanisms behind additive reduction of food intake and weight loss depends on complementary effects in brain areas regulating food intake and if restoration of leptin sensitivity is involved. MethodsDiet-induced obese (DIO) mice were co-treated with PYY(3–36) and exendin-4 (Ex4, GLP-1R agonist) for 14 days using minipumps. Leptin responsiveness was evaluated by measuring food intake and body weight after leptin injection, and gene expression profile was investigated in various of brain regions and liver. ResultsWe show that weight loss associated with co-treatment of PYY(3–36) and Ex4 and Ex4 mono-treatment in DIO mice increased expression of several genes in area postrema (AP) known to be involved in appetite regulation and Cart, Pdyn, Bdnf and Klb were synergistically upregulated by the co-treatment. The upregulations were independent of weight loss, as shown by inclusion of a weight matched control. Moreover, PYY(3–36) and Ex4 co-treatment resulted in synergistically upregulated plasma concentrations of soluble leptin receptor (SLR) and improved sensitivity to exogenous leptin demonstrated by food intake lowering. ConclusionThe study results suggest that synergistic upregulation of appetite-regulating genes in AP and improved leptin sensitivity are important mediators for the additive weight loss resulting from PYY and Ex4 co-treatment.

NPYR modulation: Potential for the next major advance in obesity and type 2 diabetes management?

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.

Comprehensive expression analysis of hormone-like substances in the subcutaneous adipose tissue of the common bottlenose dolphin Tursiops truncatus

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.

Development of Ragi Dosa Premix

Abstract: Breakfast holds significant importance as it constitutes a vital component of daily nutrition. With the rising demand for nutritious and convenient food choices, there has been an emergence of premixes tailored for traditional recipes. This project specifically targets the creation of a Ragi Dosa Premix—a dry mix designed for effortless dosa preparation using ragi (finger millet), renowned for its nutritional richness and gluten-free properties. The objective of the premix is to offer a wholesome and convenient solution for health-conscious consumers. Enriched with fiber and protein, the premix is associated with positive effects on various aspects of health including appetite regulation, weight management, body composition, and overall well-being. Additionally, it aids in mitigating the risk of developing common conditions such as heart disease and diabetes, while also promoting lower blood pressure, improved weight control, and reduced instances of constipation. Combining the nutritional benefits of three different flours—ragi, urad dal, and rice—the product is further fortified with calcium and iron compounds. Sensory and microbial analyses were conducted to evaluate the product's attributes and safety. The proximate analysis revealed key nutritional parameters such as moisture content (8.8%), total fats (2.69g/100g), protein (14.19g/100g), carbohydrates (70.27g/100g), crude fiber (2.59g/100g), ash content (1.26), calcium (190.16mg/100g), and iron (3.02mg/100g). The microbial load was found to be within acceptable limits. Organoleptic assessment, encompassing attributes like color, flavor, texture, taste, and odor, indicated favorable reception by panelists, garnering a high rating score of 8. A packaging solution was chosen based on considerations of product properties and shelf-life requirements, with the product exhibiting a shelf life of 2 months from the manufacturing date. In conclusion, the developed product offers a nutrient-rich, fiber- and protein-packed breakfast alternative, catering to health-conscious consumers.

Hypothalamic transcriptome response to simulated diel earthen pond hypoxia cycles in channel catfish (Ictalurus punctatus).

Commercial culture of channel catfish (Ictalurus punctatus) 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 with catfish subjected to 12 h of hypoxia (20% oxygen saturation; 1.8 mg O2/L; 27°C) followed by 12 h of recovery in normoxia to mimic 24 h in a catfish aquaculture pond. Fish were sampled at 0-, 6-, 12-, 18-, and 24-h timepoints, with the 6- and 12-h 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 h 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 adm, igfbp1a, igfbp7, and stc2b.NEW & NOTEWORTHY Channel catfish are an economically important species that experience diel episodic periods of hypoxia that can reduce appetite. This is the first study to investigate their transcriptome from the hypothalamus in a simulated 24-h span in a commercial catfish pond, with 12 h of hypoxia and 12 h of normoxia. The research revealed functional groups of genes relating to hypoxia, angiogenesis, and glycolysis as well as individual target genes possibly involved in appetite regulation.

Is HIV-Associated Mitochondrial Dysfunction (HIVAMD) Related to Weight Gain and Metabolic Complications on PLWH? Contribution of Ultra-processed Foods (ULPs)

Introduction With the advent of antiretroviral therapy (ART), HIV has transitioned from a fatal disease to a chronic condition, enabling people living with HIV (PLWH) to achieve life expectancies similar to those of the general population. However, PLWH experience higher rates of non-AIDS-related illnesses, particularly metabolic diseases such as insulin resistance, fatty liver, and metabolic syndrome. These conditions, collectively referred to as “inflammaging,” are attributed to chronic inflammation and immune activation, but their underlying causes remain debated. This review explores the role of ultra-processed foods (UPFs) in exacerbating HIV-associated mitochondrial dysfunction (HIVAMD) and its impact on weight gain and metabolic complications. Methods The review examines existing literature on the impact of ART on metabolic health in PLWH, differentiating between lipohypertrophy and obesity. It investigates the proposed mechanisms linking ART to metabolic dysregulation, including the effects of UPFs, especially fructose, on mitochondrial function. Data on insulin resistance, hyperinsulinemia, microbial translocation, and the potential exacerbation of these conditions by UPFs are synthesized to propose a comprehensive model. Results ART, particularly integrase strand transfer inhibitors (INSTIs), has been associated with increased visceral adipose tissue (VAT) and metabolic syndrome. Proposed mechanisms include ART-induced alterations in appetite regulation, insulin signaling, and energy expenditure. HIVAMD is identified as a key factor in metabolic complications, with UPFs contributing to mitochondrial dysfunction, insulin resistance, and microbial translocation. Fructose overconsumption is highlighted for its role in liver inflammation, fatty liver, and metabolic syndrome through mechanisms such as ATP depletion, NAD+ depletion, and oxidative stress. Conclusion PLWH are at increased risk of metabolic complications due to the combined effects of HIVAMD and the consumption of UPFs. Addressing these issues requires prospective clinical trials to evaluate dietary interventions and nutritional supplements. Lifestyle modifications, such as intermittent fasting and pharmacological measures, may mitigate these complications. Community-based research initiatives are essential for developing and implementing effective interventions to improve the metabolic health of PLWH.

Genetics, pharmacotherapy, and dietary interventions in childhood obesity.

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.

Excessive sucrose consumption reduces synaptic density and increases cannabinoid receptors in Göttingen minipigs

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 [3H]raclopride on dopamine D2/3 receptors, [3H]UCB-J at synaptic vesicle glycoprotein 2A (SV2A), [3H]MPEPγ at metabotropic glutamate receptor subtype 5 (mGluR5) and [3H]SR141716A at the cannabinoid receptor 1 (CB1). Compared to control diet animals, the sucrose group showed significantly lower [3H]UCB-J and [3H]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.

Is hepatic GABA transaminase a promising target for obesity and epilepsy treatments?

γ-Aminobutyric acid (GABA) transaminase (GABA-T) is a GABA-degrading enzyme that plays an essential role in regulating GABA levels and maintaining supplies of GABA. Although GABA in the mammalian brain was discovered 70 years ago, research on GABA and GABA-T has predominantly focused on the brain. Notwithstanding the high activity and expression of GABA-T in the liver, the exact functions of GABA-T in the liver remain unknown. This article reviews the up-to-date information on GABA-T in the liver. It presents recent findings on the role of liver GABA-T in food intake suppression and appetite regulation. Finally, the potential functions of liver GABA-T in other neurological diseases, natural GABA-T inhibitors, and future perspectives in this research area are discussed.

Effect of intracerebroventricular (ICV) injection of adrenomedullin and its interaction with NPY and CCK pathways on food intake regulation in neonatal layer-type chicks

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 (NPY1 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 (NPY2 receptor antagonist, 1.25 µg), SML0891 (NPY5 receptor antagonist, 1.25 µg) and CCK4 (1 nmol) were injected instead of B5063. In experiment 6, ICV injection of saline and CCK8s (0.125, 0.25, and 0.5 nmol) were done. In experiment 7, chickens injected with saline, CCK8s (0.125 nmol), adrenomedullin (3 nmol) and co-injection of CCK8s+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 CCK8s (0.25 and 0.5 nmol) reduced food intake (P < 0.05). Co-injection of the CCK8s+adrenomedullin significantly potentiated adrenomedullin-induced hypophagia (P < 0.05). Administration of the SF22, SML0891 and CCK4 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 NPY1 and CCK8s receptors. However, our novel results should form the basis for future experiments.

1 The role of gut microbiota on regulation of growth and metabolism by branched-chain amino acids

Abstract Branched-chain amino acids (BCAA) including leucine, isoleucine and valine are essential amino acids, which are involved in energy homeostasis and regulation of many physiological paradigms including growth. The BCAA serve not only as an essential substrate in the synthesis of body proteins, but also have an important role in regulation of protein turnover. The effects of BCAA on growth and metabolism are likely mediated through different pathways including shifts in metabolic profile in peripheral organs, oxidative capacity of muscle, gut development, and protein metabolism in muscle. Although it has not been appropriately studied or fully dissected, the impact of BCAA on growth and metabolism is thought to lie in the alteration of gut microbiota by BCAA. It has long been believed that gut microbiota, more specifically, the activity of the microbiome and its metabolic products, directly influence a variety of aspects in metazoan physiology. For example, deregulation of bacterial community structure has been linked with host longevity and stress resistance, the pathogenesis of several disorders, regulation of appetite. Multiple studies have demonstrated that modulation of dietary BCAA levels could elicit clear shifts in gut microbial community structure. As part of “Physiology Symposium: The Microbiome and the Host: Functional Role in Metabolism, Immunity, and Gut-Brain Axis”, the possible involvement of intestinal microbiota on regulatory roles of BCAA on growth and metabolism will be discussed.

No Effect of High Eating Frequency Compared with Low Eating Frequency on Appetite and Inflammation Biomarkers: Results from a Randomized Crossover Clinical Trial

BackgroundEating frequency (EF) focuses on the total number of eating occasions per day and may influence metabolic health. ObjectivesWe sought to examine the effect of high compared with low EF on appetite regulation and inflammatory biomarkers among healthy adults. MethodsData are from a randomized, crossover trial (the Frequency of Eating and Satiety Hormones study). Participants (n = 50) completed 2 isocaloric 21-d study periods of low EF (3 eating occasions/d) and high EF (6 eating occasions/d) in random order with a 14-d washout period in between. Participants were free-living and consumed their own food, using study-directed, structured meal plans with identical foods and total energy in both study periods. On days 1 and 21 of each EF period, fasting blood was collected during in-person clinic visits to assess plasma concentrations of ghrelin, leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP). Linear mixed models with EF, diet sequence, and period as fixed effects and participant as random effect were used to estimate the intervention effect. Interaction effects between EF and body fat percentage were examined. ResultsAmong the 50 participants who completed the trial, 39 (78%) were women, 30 (60%) were Non-Hispanic White, and 40 (80%) had a body mass index of <25 kg/m2, and the mean age was 32.1 y. The differences between high and low EF in fasting ghrelin (geometric mean difference: 17.76 ng/mL; P = 0.60), leptin (geometric mean difference: 2.09 ng/mL; P = 0.14), adiponectin (geometric mean difference: 381.7 ng/mL; P = 0.32), and hs-CRP (geometric mean difference: −0.018 mg/dL; P = 0.08) were not statistically significant. No significant interaction was observed between EF and body fat percentage on appetite regulation and inflammatory biomarkers. ConclusionsNo differences was observed in fasting ghrelin, leptin, adiponectin, and hs-CRP comparing high and low EF. Future studies are needed to understand the physiology of EF and appetite as they relate to metabolic health.This trial was registered at clinicaltrials.gov as NCT02392897.

Effects of fasting and environmental factors on appetite regulators in pond loach Misgurnus anguillicaudatus

The pond loach (Misgurnus anguillicaudatus) is an important aquaculture freshwater species, used as an ornamental fish, food source for humans and angling bait. Pond loaches are resistant to fasting and extreme environmental conditions, including temperature and low oxygen levels. Little is known about how these factors affect the feeding physiology and the endocrine regulation of feeding of loaches. In this study, we examined the effects of fasting, as well as increased temperature and decreased oxygen levels on food intake and transcript levels of appetite regulators. Fasted fish had lower blood glucose levels, and lower expression levels of intestine CCK and PYY, and brain CART1, but had higher levels of brain orexin and ghrelin than fed fish. Fish held at 30 °C had higher food intake, glucose levels, and mRNA levels of intestine CCK and PYY, and brain CART2, but lower brain orexin levels than fish at 20 °C. Fish held at low oxygen levels had a lower food intake, higher intestine CCKa and ghrelin, and brain orexin, CART2 and ghrelin mRNA expression levels than fish held at high O2 levels. Our results suggest that fasting and high temperatures increase the expression of orexigenic and anorexigenic factors respectively, whereas the increase in expression of both orexigenic and anorexigenic factors in low O2 environments might not be related to their role in feeding, but possibly to protection from tissue damage. The results of our study might shed new light on how pond loaches are able to cope with extreme environmental conditions such as low food availability, extreme temperatures and hypoxia.

Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease.

GDF-15 is an essential member of the transforming growth factor-beta superfamily. Its functions mainly involve in tissue injury, inflammation, fibrosis, regulation of appetite and weight, development of tumor, and cardiovascular disease. GDF-15 is involved in various signaling pathways, such as MAPK pathway, PI3K/AKT pathway, STAT3 pathway, RET pathway, and SMAD pathway. In addition, several factors such as p53, ROS, and TNF-α participate the regulation of GDF-15. However, the specific mechanism of these factors regulating GDF-15 is still unclear and more research is needed to explore them. GDF-15 mainly improves the function of kidneys in CKD and plays an important role in the prediction of CKD progression and cardiovascular complications. In addition, the role of GDF-15 in the kidney may be related to the SMAD and MAPK pathways. However, the specific mechanism of these pathways remains unclear. Accordingly, more research on the specific mechanism of GDF-15 affecting kidney disease is needed in the future. In conclusion, GDF-15 may be a therapeutic target for kidney disease.

Fat loss and muscle gain: The possible role of cortical glutamate in determining the efficacy of physical exercise

BackgroundPhysical exercise is widely acknowledged for its health benefits, but its effectiveness in treating obesity remains contentious due to variability in response. Owing to the roles of glutamate in appetite regulation, food addiction, and impulsivity, this observational cohort-study evaluated medial prefrontal cortex (mPFC) glutamate as a predictor of variability in exercise response, specifically in terms of fat loss and muscle gain. MethodsHealthy non-exercising adult men (n = 21) underwent an 8-week supervised exercise program. Baseline glutamate levels in the mPFC were measured through magnetic resonance spectroscopy. For exercise-dependent changes in body composition (fat and muscle mass), basal metabolic rate (BMR), and blood metabolic biomarkers related to lipid and glucose metabolism, measurements were obtained through bioelectrical impedance and blood sample analyses, respectively. ResultsThe exercise program resulted in significant improvements in body composition, including reductions in percentage body fat mass, body fat mass, and waist-to-hip ratio and an increase in mean muscle mass. Furthermore, BMR and metabolic indicators linked to glucose and lipids exhibited significant changes. Notably, lower baseline glutamate levels were associated with greater loss in percentage body fat mass (r = 0.482, p = 0.027), body fat mass (r = 0.441, p = 0.045), and increase in muscle mass (r = −0.409, p = 0.066, marginal) following the exercise program. ConclusionThese preliminary findings contribute to our understanding of the neurobiology of obesity and emphasize the significance of glutamate in regulating body composition. The results also highlight cortical glutamate as a potential predictor of exercise-induced fat loss and muscle gain.

Metabolic liability for weight gain in early adulthood

While weight gain is associated with a host of chronic illnesses, efforts in obesity have relied on single "snapshots" of body mass index (BMI) to guide genetic and molecular discovery. Here, we study >2,000 young adults with metabolomics and proteomics to identify a metabolic liability to weight gain in early adulthood. Using longitudinal regression and penalized regression, we identify a metabolic signature for weight liability, associated with a 2.6% (2.0%-3.2%, p= 7.5×10-19) gain in BMI over≈20 years per SD higher score, after comprehensive adjustment. Identified molecules specified mechanisms of weight gain, including hunger and appetite regulation, energy expenditure, gut microbial metabolism, and host interaction with external exposure. Integration of longitudinal and concurrent measures in regression with Mendelian randomization highlights the complexity of metabolic regulation of weight gain, suggesting caution in interpretation of epidemiologic or genetic effect estimates traditionally used in metabolic research.