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Revista Da Associacao Medica Brasileira... 2024Diet and exercise, which are the building blocks of obesity management, provide weight loss by creating a negative energy balance. However, the effect of energy deficit...
OBJECTIVE
Diet and exercise, which are the building blocks of obesity management, provide weight loss by creating a negative energy balance. However, the effect of energy deficit induced by long-term diet and exercise on appetite hormones remains unclear. The study was designed to determine the effect of a 12-week diet and exercise program applied to obese individuals on the levels of appetite hormones, namely, ghrelin, GLP-1, and PYY.
METHODS
A total of 62 obese individuals (BMI≥30) and 48 healthy controls (BMI 18.50-29.99) participated in the study. Appropriate diet (1000-1500 kcal/day) and exercise (at least 5000 steps/day) programs were applied to obese individuals according to age, gender, and BMI. The ghrelin, GLP-1, and PYY values of the participants were analyzed by the ELISA method and commercial kit by taking venous blood samples before and after 12 weeks of treatment.
RESULTS
While ghrelin levels of individuals decreased significantly after diet and exercise, PYY levels increased significantly. However, despite the treatment applied, the GLP-1 and PYY levels of the case group did not reach the levels of the control group.
CONCLUSION
Long-term diet and exercise intervention had a positive effect on appetite regulation hormones. It reduced ghrelin levels after treatment. Associated weight loss was facilitated. In the case group, increased satiety hormones after combined treatment supported the maintenance of body weight by increasing satiety.
Topics: Humans; Ghrelin; Glucagon-Like Peptide 1; Peptide YY; Obesity; Weight Loss; Diet
PubMed: 38511748
DOI: 10.1590/1806-9282.20230263 -
Annals of Nutrition & Metabolism 2024The ghrelin system, which generates the appetite hormone, is harmed by obesity, a problem of worldwide public health. An efficient way to cure obesity is through... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The ghrelin system, which generates the appetite hormone, is harmed by obesity, a problem of worldwide public health. An efficient way to cure obesity is through bariatric surgery. This randomized controlled study's objective was to assess preoperative diet-related DNA methylation of Ghrelin (GHRL) levels in patients undergoing bariatric surgery.
METHODS
The 50 patients who volunteered to participate in the trial were randomly divided into two groups. The study group followed the very low-calorie diet for 2 weeks. The control group did not follow any diet. The physiological parameters, weight, and DNA methylation levels of the patients were assessed.
RESULTS
The percentage of excess weight loss (EWL) in the control and study groups was determined as 47.1% and 51.5%, respectively. The study group's GHRL percentage of methylated reference was 76.8%, whereas the control group's was 67.3%. It was concluded that the EWL and GHRL gene DNA methylation of the diet-treated study group were significantly higher than the control group (p < 0.05).
CONCLUSION
According to the findings, the pre-op diet had a favorable effect on the patient's behavior modification. It has also been shown to increase postoperative weight loss and DNA methylation of the Ghrelin gene. The ghrelin gene has been muted by methylation, making hunger regulation more manageable.
Topics: Humans; Ghrelin; DNA Methylation; Bariatric Surgery; Female; Male; Adult; Weight Loss; Middle Aged; Caloric Restriction; Obesity, Morbid
PubMed: 38498987
DOI: 10.1159/000538406 -
Physiological Reports Mar 2024The brain possesses intricate mechanisms for monitoring sodium (Na) levels in body fluids. During prolonged dehydration, the brain detects variations in body fluids and... (Review)
Review
The brain possesses intricate mechanisms for monitoring sodium (Na) levels in body fluids. During prolonged dehydration, the brain detects variations in body fluids and produces sensations of thirst and aversions to salty tastes. At the core of these processes Na , the brain's Na sensor, exists. Specialized neural nuclei, namely the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), which lack the blood-brain barrier, play pivotal roles. Within the glia enveloping the neurons in these regions, Na collaborates with Na /K -ATPase and glycolytic enzymes to drive glycolysis in response to elevated Na levels. Lactate released from these glia cells activates nearby inhibitory neurons. The SFO hosts distinct types of angiotensin II-sensitive neurons encoding thirst and salt appetite, respectively. During dehydration, Na -activated inhibitory neurons suppress salt-appetite neuron's activity, whereas salt deficiency reduces thirst neuron's activity through cholecystokinin. Prolonged dehydration increases the Na sensitivity of Na via increased endothelin expression in the SFO. So far, patients with essential hypernatremia have been reported to lose thirst and antidiuretic hormone release due to Na -targeting autoantibodies. Inflammation in the SFO underlies the symptoms. Furthermore, Na activation in the OVLT, driven by Na retention, stimulates the sympathetic nervous system via acid-sensing ion channels, contributing to a blood pressure elevation.
Topics: Humans; Sodium; Thirst; Blood Pressure; Appetite; Dehydration; Sodium Chloride; Brain; Sodium Chloride, Dietary
PubMed: 38479999
DOI: 10.14814/phy2.15970 -
International Journal of Molecular... Feb 2024In the field of nutritional science and metabolic disorders, there is a growing interest in natural bitter compounds capable of interacting with bitter taste receptors... (Randomized Controlled Trial)
Randomized Controlled Trial
In the field of nutritional science and metabolic disorders, there is a growing interest in natural bitter compounds capable of interacting with bitter taste receptors (TAS2Rs) useful for obesity management and satiety control. This study aimed to evaluate the effect of a nutraceutical formulation containing a combination of molecules appropriately designed to simultaneously target and stimulate these receptors. Specifically, the effect on CCK release exerted by a multi-component nutraceutical formulation ( bark, , and roots in a 1:1:1 ratio, named Gengricin) was investigated in a CaCo-2 cell line, in comparison with alone. In addition, these nutraceutical formulations were tested through a 3-month randomized controlled trial (RCT) conducted in subjects who were overweight-obese following a hypocaloric diet. Interestingly, the Gengricin group exhibited a significant greater weight loss and improvement in body composition than the Placebo and groups, indicating its effectiveness in promoting weight regulation. Additionally, the Gengricin group reported higher satiety levels and a significant increase in serum CCK levels, suggesting a physiological basis for the observed effects on appetite control. Overall, these findings highlight the potential of natural nutraceutical strategies based on the combination of bitter compounds in modulating gut hormone release for effective appetite control and weight management.
Topics: Adult; Humans; Overweight; Appetite; Obesity; Appetite Regulation; Dietary Supplements
PubMed: 38473841
DOI: 10.3390/ijms25052596 -
BMJ Open Mar 2024Obesity increases the risk of morbidity and mortality. A major driver has been the increased availability of ultra-processed food (UPF), now the main UK dietary energy...
UPDATE trial: investigating the effects of ultra-processed versus minimally processed diets following UK dietary guidance on health outcomes: a protocol for an 8-week community-based cross-over randomised controlled trial in people with overweight or obesity, followed by a 6-month behavioural...
INTRODUCTION
Obesity increases the risk of morbidity and mortality. A major driver has been the increased availability of ultra-processed food (UPF), now the main UK dietary energy source. The UK Eatwell Guide (EWG) provides public guidance for a healthy balanced diet but offers no UPF guidance. Whether a healthy diet can largely consist of UPFs is unclear. No study has assessed whether the health impact of adhering to dietary guidelines depends on food processing. Furthermore, our study will assess the impact of a 6-month behavioural support programme aimed at reducing UPF intake in people with overweight/obesity and high UPF intakes.
METHODS AND ANALYSIS
UPDATE is a 2×2 cross-over randomised controlled trial with a 6-month behavioural intervention. Fifty-five adults aged ≥18, with overweight/obesity (≥25 to <40 kg/m), and ≥50% of habitual energy intake from UPFs will receive an 8-week UPF diet and an 8-week minimally processed food (MPF) diet delivered to their home, both following EWG recommendations, in a random order, with a 4-week washout period. All food/drink will be provided. Participants will then receive 6 months of behavioural support to reduce UPF intake. The primary outcome is the difference in weight change between UPF and MPF diets from baseline to week 8. Secondary outcomes include changes in diet, waist circumference, body composition, heart rate, blood pressure, cardiometabolic risk factors, appetite regulation, sleep quality, physical activity levels, physical function/strength, well-being and aspects of behaviour change/eating behaviour at 8 weeks between UPF/MPF diets, and at 6-month follow-up. Quantitative assessment of changes in brain MRI functional resting-state connectivity between UPF/MPF diets, and qualitative analysis of the behavioural intervention for feasibility and acceptability will be undertaken.
ETHICS AND DISSEMINATION
Sheffield Research Ethics Committee approved the trial (22/YH/0281). Peer-reviewed journals, conferences, PhD thesis and lay media will report results.
TRIAL REGISTRATION NUMBER
NCT05627570.
Topics: Adult; Humans; Overweight; Obesity; Diet; Energy Intake; United Kingdom; Randomized Controlled Trials as Topic
PubMed: 38471681
DOI: 10.1136/bmjopen-2023-079027 -
Frontiers in Insect Science 2024To maintain energetic homeostasis the energetic state of the individual needs to communicate with appetite regulatory mechanisms on a regular basis. Although hunger...
INTRODUCTION
To maintain energetic homeostasis the energetic state of the individual needs to communicate with appetite regulatory mechanisms on a regular basis. Although hunger levels indicated by the energetic state and appetite levels, the desire for food intake, tend to be correlated, and on their own are well studied, how the two cross-talk and regulate one another is less known. Insects, in contrast to vertebrates, tend to have trehalose as the primary sugar found in the hemolymph, which could possibly serve as an alternative monitor of the energetic state in comparison to the glucose-insulin signaling pathway, found in vertebrates.
METHODS
We investigate how manipulating hemolymph sugar levels alter the biogenic amines in the honey bee brain, appetite levels, and insulin like peptide gene expression, across three age classes, to determine how the energetic state of the honey bee might be connected to appetite regulation.
RESULTS
We found that only in the forager bees, with a lowering of hemolymph trehalose levels, there was an increase in octopamine and a decrease in tyramine levels in the honey bee brain that corresponded with increased appetite levels, while there was no significant changes in gene expression.
DISCUSSION
Our findings suggest that hemolymph trehalose levels aid in regulating appetite levels, in forager bees, via octopamine and tyramine, and this regulation appears to be functioning independent of the glucose insulin signaling pathway. Whether this potentially more direct and rapid appetite regulatory pathway can be generalized to other insects, which also undergo energy demanding activities, remains to be investigated.
PubMed: 38469335
DOI: 10.3389/finsc.2024.1335350 -
Applied and Environmental Microbiology Apr 2024Humans and mammals need to ingest essential amino acids (EAAs) for protein synthesis. In addition to their importance as nutrients, EAAs are involved in brain...
Humans and mammals need to ingest essential amino acids (EAAs) for protein synthesis. In addition to their importance as nutrients, EAAs are involved in brain homeostasis. However, elderly people are unable to efficiently consume EAAs from their daily diet due to reduced appetite and variations in the contents of EAAs in foods. On the other hand, strains of the yeast that accumulate EAAs would enable elderly people to intakegest adequate amounts of EAAs and thus might slow down the neurodegenerative process, contributing to the extension of their healthy lifespan. In this study, we isolated a mutant (strain HNV-5) that accumulates threonine, an EAA, derived from a diploid laboratory yeast by conventional mutagenesis. Strain HNV-5 carries a novel mutation in the gene encoding the Ala462Thr variant of aspartate kinase (AK). Enzymatic analysis revealed that the Ala462Thr substitution significantly decreased the sensitivity of AK activity to threonine feedback inhibition even in the presence of 50 mM threonine. Interestingly, Ala462Thr substitution did not affect the catalytic ability of Hom3, in contrast to previously reported amino acid substitutions that resulted in reduced sensitivity to threonine feedback inhibition. Furthermore, yeast cells expressing the Ala462Thr variant showed an approximately threefold increase in intracellular threonine content compared to that of the wild-type Hom3. These findings will be useful for the development of threonine-accumulating yeast strains that may improve the quality of life in elderly people.IMPORTANCEFor humans and mammals, essential amino acids (EAAs) play an important role in maintaining brain function. Therefore, increasing the intake of EAAs by using strains of the yeast that accumulate EAAs may inhibit neurodegeneration in elderly people and thus contribute to extending healthy lifespan and improving their quality of life. Threonine, an EAA, is synthesized from aspartate. Aspartate kinase (AK) catalyzes the first step in threonine biosynthesis and is subject to allosteric regulation by threonine. Here, we isolated a threonine-accumulating mutant of by conventional mutagenesis and identified a mutant gene encoding a novel variant of AK. In contrast to previously isolated variants, the Hom3 variant exhibited AK activity that was insensitive to feedback inhibition by threonine but retained its catalytic ability. This resulted in increased production of threonine in yeast. These findings open up the possibility for the rational design of AK to increase threonine productivity in yeast.
Topics: Humans; Animals; Aged; Saccharomyces cerevisiae; Threonine; Aspartate Kinase; Feedback; Quality of Life; Mammals
PubMed: 38456673
DOI: 10.1128/aem.00155-24 -
Nature Communications Mar 2024Nicotinamide adenine dinucleotide (NAD) serves as a crucial coenzyme in numerous essential biological reactions, and its cellular availability relies on the activity of...
Nicotinamide adenine dinucleotide (NAD) serves as a crucial coenzyme in numerous essential biological reactions, and its cellular availability relies on the activity of the nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed salvage pathway. Here we show that treatment with saturated fatty acids activates the NAD salvage pathway in hypothalamic astrocytes. Furthermore, inhibition of this pathway mitigates hypothalamic inflammation and attenuates the development of obesity in male mice fed a high-fat diet (HFD). Mechanistically, CD38 functions downstream of the NAD salvage pathway in hypothalamic astrocytes burdened with excess fat. The activation of the astrocytic NAMPT-NAD-CD38 axis in response to fat overload induces proinflammatory responses in the hypothalamus. It also leads to aberrantly activated basal Ca signals and compromised Ca responses to metabolic hormones such as insulin, leptin, and glucagon-like peptide 1, ultimately resulting in dysfunctional hypothalamic astrocytes. Our findings highlight the significant contribution of the hypothalamic astrocytic NAD salvage pathway, along with its downstream CD38, to HFD-induced obesity.
Topics: Male; Mice; Animals; NAD; Dietary Fats; Astrocytes; Obesity; Hypothalamus; Cytokines
PubMed: 38453901
DOI: 10.1038/s41467-024-46009-0 -
Neurobiology of Disease Apr 2024Recent research highlights the profound impact of the gut microbiome on neuropsychiatric disorders, shedding light on its potential role in shaping human behavior. In...
Influence of the gut microbiome on appetite-regulating neuropeptides in the hypothalamus: Insight from conventional, antibiotic-treated, and germ-free mouse models of anorexia nervosa.
Recent research highlights the profound impact of the gut microbiome on neuropsychiatric disorders, shedding light on its potential role in shaping human behavior. In this study, we investigate the role of the gut microbiome in appetite regulation using activity-based anorexia (ABA) mouse model of anorexia nervosa (AN) - a severe eating disorder with significant health consequences. ABA was induced in conventional, antibiotic-treated, and germ-free mice. Our results show the clear influence of the gut microbiome on the expression of four orexigenic (neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, and orexin) and four anorexigenic peptides (cocaine- and amphetamine-regulated transcript, corticotropin-releasing hormone, thyrotropin-releasing hormone, and pro-opiomelanocortin) in the hypothalamus. Additionally, we assessed alterations in gut barrier permeability. While variations were noted in germ-free mice based on feeding and activity, they were not directly attributable to the gut microbiome. This research emphasizes that the gut microbiome is a pivotal factor in AN's appetite regulation beyond just dietary habits or physical activity.
Topics: Humans; Mice; Animals; Appetite; Anorexia Nervosa; Gastrointestinal Microbiome; Neuropeptides; Hypothalamus
PubMed: 38432539
DOI: 10.1016/j.nbd.2024.106460 -
Neuropeptides Jun 2024The neuropeptide Y receptor (YR), a rhodopsin-like G protein-coupled receptor (GPCR) and the hormone pancreatic polypeptide (PP) are members of the neuropeptide Y family... (Review)
Review
The neuropeptide Y receptor (YR), a rhodopsin-like G protein-coupled receptor (GPCR) and the hormone pancreatic polypeptide (PP) are members of the neuropeptide Y family consisting of four receptors (YR, YR, YR, YR) and three highly homologous peptide ligands (neuropeptide Y, peptide YY, PP). In this family, the YR is of particular interest as it is the only subtype with high affinity to PP over NPY. The YR, as a mediator of PP signaling, has a pivotal role in appetite regulation and energy homeostasis, offering potential avenues for the treatment of metabolic disorders such as obesity. PP as anorexigenic peptide is released postprandial from the pancreas in response to food intake, induces satiety signals and contributes to hamper excessive food intake. Moreover, this system was also described to be associated with different types of cancer: overexpression of YR have been found in human adenocarcinoma cells, while elevated levels of PP are related to the development of pancreatic endocrine tumors. The pharmacological relevance of the YR advanced the search for potent and selective ligands for this receptor subtype, which will be significantly progressed through the elucidation of the active state PP-YR cryo-EM structure. This review summarizes the development of novel PP-derived ligands, like Obinepitide as dual YR/YR agonist in clinical trials or UR-AK86c as small hexapeptide agonist with picomolar affinity, as well as the first allosteric modulators that selectively target the YR, e.g. VU0506013 as potent YR positive allosteric modulator or (S)-VU0637120 as allosteric antagonist. Here, we provide valuable insights into the complex physiological functions of the YR and PP and the pharmacological relevance of the system in appetite regulation to open up new avenues for the development of tool compounds for targeted therapies with potential applications in metabolic disorders.
Topics: Humans; Pancreatic Polypeptide; Receptors, Neuropeptide Y; Animals; Ligands
PubMed: 38430725
DOI: 10.1016/j.npep.2024.102416