Adolescence represents a critical window of metabolic plasticity, during which profound hormonal, neurobiological, and physiological remodelling increases susceptibility to nutritional exposures. In parallel with the rising prevalence of obesity, insulin resistance, metabolic syndrome, and non-alcoholic fatty liver disease among young people, there is growing interest in the potential for functional food components to modulate epigenetic pathways that govern metabolic programming. This narrative review synthesises current evidence (2015-2025) from PubMed, Scopus, Web of Science, and Embase to elucidate how diet-derived bioactive compounds influence epigenetic regulation relevant to adipogenesis, appetite control, insulin signalling, and lipid homeostasis during adolescence. Particular emphasis is placed on molecular mechanisms, including DNA methylation changes in genes regulating adipocyte differentiation, hypothalamic neuropeptide expression, and pancreatic β-cell function; histone modifications, such as acetylation and methylation events that remodel chromatin accessibility in metabolic tissues; and modulation of microRNA networks implicated in lipid metabolism, inflammatory signalling, and insulin secretion. Furthermore, the review examines the interplay between diet, the gut microbiota, and the epigenome, highlighting the role of microbially derived short-chain fatty acids (SCFAs) as endogenous histone deacetylase inhibitors and mediators of epigenetic remodelling in adipose tissue. By linking these mechanisms to specific functional food components, including polyphenols, long-chain omega-3 fatty acids, fermentable dietary fibre, and other bioactive molecules, we demonstrate how nutritional signals can counteract maladaptive metabolic trajectories and potentially reduce the intergenerational transmission of metabolic risk. A deeper understanding of these epigenetic effects provides the foundation for developing personalised nutrition strategies aimed at preventing metabolic disorders from emerging during adolescence and beyond.

Background Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist primarily used to improve glycemic control in patients with type 2 diabetes mellitus (T2DM). It is also recommended as part of the therapeutic strategy for individuals with metabolic syndrome or obesity. This study aimed to evaluate the effects of semaglutide administration on body weight reduction, eating behaviors, energy intake, and appetite control in women with diagnosed obesity and insulin resistance. Material and methods The study included 104 women diagnosed with obesity and insulin resistance who tolerated semaglutide therapy without adverse effects. Results Participants using semaglutide demonstrated a mean decrease in daily energy intake of 103 kcal (p=0.034; d=-0.21) compared with baseline. A significant reduction in body weight (mean -2.85 kg) was observed, along with decreases in body fat content, Body Mass Index (BMI), and waist-to-hip ratio (WHR). Conclusions Semaglutide use was associated with appetite suppression, reduced snacking frequency, and a subsequent decrease in body weight and body fat percentage, indicating its beneficial role in weight management among women with obesity and insulin resistance.

Obesity, defined as excessive fat accumulation that impairs health, is a global challenge with high mortality rates. Sibutramine, a centrally acting anorectic, was widely used in obesity treatment due to its effects on appetite control and weight loss. It represented a key step in anti-obesity pharmacotherapy before being withdrawn in many countries. This study evaluates how a high sibutramine dose (10 mg.kg.day-1 followed by 13 mg.kg.day-1) influences body weight, biochemical profiles, liver and intestinal health, and gut microbiota composition in rats subjected to a cafeteria diet for 16 weeks. Rats treated with sibutramine exhibited a 10.93% reduction in body weight and improved glycemic control compared to untreated groups. Sibutramine modulated lipid profiles by lowering total cholesterol and increasing HDL levels in controlled diet groups. The treatment attenuated liver damage markers (AST and ALT) and increased intestinal crypt depth, suggesting gut integrity. The elevated sibutramine dose led to distinct microbiota shifts, partially reversing cafeteria diet-induced dysbiosis by increasing SCFA-producing genera, including Bacillus, Marvinbryantia, and Bifidobacterium. However, dietary factors remained the dominant driver of microbial composition. These findings underscore the impact of sibutramine's dosing on gut microbiota and reinforce its role in obesity-related health improvements.

Growing evidence supports early eating to control appetite and energy balance but there are few controlled studies to assess the amount and/or type of breakfast meal. This randomized, within-participant, diet intervention examined the effects of higher-fibre (HF) and higher-protein (HP) breakfasts in adults with overweight/obesity. Nineteen healthy adults consumed two randomized 28 day weight loss (WL) diets; as higher-fibre (HFWL) or higher protein (HPWL), with all food provided. Both WL diets were designed as 45%, 35% and 20% of calories to be consumed at the morning, afternoon and evening, respectively. The primary outcome was energy balance, analysed by body weight changes. The secondary outcomes were gut health (assessed by changes in faecal microbiota composition and microbial metabolite concentrations) and subjective appetite assessed with visual analogue scales (VAS). There was a diet effect on WL, with mean loss of -4.87 kg and -3.87 kg for the HFWL and HPWL diets, respectively (P=0.002). The HPWL diet was superior to the HFWL diet for suppressing subjective appetite (P=0.003). The faecal microbiota analysis showed beneficial groups of bacteria, including bifidobacteria, and the butyrate-producers Faecalibacterium and Roseburia, were significantly increased in proportional abundance on the HFWL diet. Breakfast composition has an important role in influencing subjective appetite with the higher-protein diet promoting greater feelings of satiety. The proportional abundance of putatively beneficial groups of gut microbiota was markedly higher on the fibre-enriched diet, which may be preferable for gut health.

Physical activity promotes gut adaptation, nutrient responsiveness, and sensitivity to gut peptides in male mice.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin important for neuronal survival and synaptic plasticity that also plays a role in metabolic regulation (energy homeostasis and appetite control). Lower circulating BDNF levels have been associated with obesity, metabolic risk factors, and poorer cognitive and mental health outcomes, whereas higher levels are linked to more favorable profiles. In this study we sought to systematically evaluate the effects of dietary weight-loss interventions on circulating BDNF levels in adults with overweight or obesity. A comprehensive literature search of PubMed, Web of Science, Scopus, and Google Scholar was conducted from inception through April 2025 to identify clinical trials investigating dietary weight-loss or calorie-restriction interventions in adults with overweight or obesity that reported data regarding circulating BDNF outcomes. Eligible studies were clinical trials with interventions lasting ≥4 weeks to investigate circulating BDNF concentrations before and after dietary interventions that were conducted in adults (≥18 years old) with baseline overweight or obesity. This systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Risk of bias was assessed using the Cochrane risk-of-bias tool. Data on study design, participant characteristics, dietary interventions, and BDNF outcomes were extracted and synthesized qualitatively. A summary table of the included studies was generated. Fifteen clinical studies (n = 862 total participants) met inclusion criteria (11 randomized trials and 4 single-arm trials). Diet modalities included continuous calorie restriction (typically 20%-30% caloric deficit), intermittent fasting (eg, alternate-day fasting, time-restricted eating), ketogenic diets (KDs), Mediterranean-type diets, and other weight-loss diets. Duration of interventions ranged from 6 to 26 weeks. Responses to BDNF varied by intervention. In adults with overweight/obesity, weight-loss dietary interventions demonstrated heterogeneous effects on circulating BDNF. We categorized the included studies into 3 groups based on the effects of dietary weight loss on BDNF: increases, no significant change, or decreases. Approximately half of the studies showed no significant effect, while a few interventions showed a decrease. Intermittent fasting regimens and certain dietary patterns (eg, the Mediterranean-DASH [Dietary Approaches to Stop Hypertension] [MIND] diet, and the KD) tend to elevate BDNF levels, whereas continuous calorie restriction often shows no change, and very rapid weight loss may paradoxically reduce BDNF in some cases. These findings suggest that diet-induced weight loss can influence neurotrophic status, potentially modulating brain health. However, results are inconsistent across studies. Overall, interventions involving intermittent calorie restriction, MIND, and/or KD, more frequently reported BDNF increases, whereas continuous calorie restriction produced mixed results.

N-lactoyl-phenylalanine (Lac-Phe) has emerged as a signaling metabolite connecting cellular metabolism to systemic physiology. Synthesized through carnosine dipeptidase 2-mediated conjugation of lactate and phenylalanine, Lac-Phe increases acutely in response to exercise and feeding, the primary drivers of its elevation under physiologic conditions. In preclinical models, Lac-Phe acts as a potent regulator of energy balance. Its administration suppresses appetite and reduces body weight in obesity, whereas pharmacologic interventions such as metformin elevate circulating Lac-Phe to produce similar anorexigenic effects. Converging evidence implicates central mechanisms, including inhibition of orexigenic agouti-related peptide neurons, positioning Lac-Phe as a mediator linking peripheral metabolic signals to appetite control. The first human Lac-Phe clinical trial in individuals with obesity began dosing in 2025, evaluating appetite suppression and glucose-lowering effects. Beyond metabolism, Lac-Phe promotes anti-inflammatory macrophage polarization, conferring protection in murine models of colitis and spinal cord injury. Circulating Lac-Phe also rises in conditions such as mitochondrial dysfunction, sepsis, and phenylketonuria, suggesting broader associations with perturbed energy metabolism and systemic stress responses. This review integrates current knowledge spanning molecular mechanisms, physiological regulation, and clinical translation. We examine Lac-Phe biosynthesis, tissue distribution, and regulatory patterns across physiological and disease states, and highlight emerging mechanisms of action in metabolic and inflammatory signaling. Finally, we discuss key knowledge gaps, highlighting the need to define targets, transporters, and tissue sources to shape the next phase of discovery. Collectively, these advances position Lac-Phe at the forefront of exerkine biology and as a promising molecular link between metabolism, immunity, and therapeutic innovation. SIGNIFICANCE STATEMENT: Evidence across molecular, physiological, and translational domains positions Lac-Phe as a promising therapeutic target. This review frames our understanding of Lac-Phe biology-from its biosynthesis to its roles in energy balance and outlines the key questions that will define ongoing discovery.

Background: South Africa faces the world’s highest HIV burden, disproportionately affecting women, alongside rising Type 2 Diabetes (T2D). Weight gain associated with preferred dolutegravir (DTG)-based antiretroviral therapy may worsen obesity and T2D risk. This process evaluation explored the implementation of a 12-month time-restricted eating (TRE) intervention for weight management in women with HIV and overweight/obesity in Khayelitsha, Cape Town. Methods: Using the RE-AIM framework, the study investigated the implementation journey. Data were collected from three groups: RCT participants, healthcare workers (n = 21), and fieldworkers (n = 3). Methods included structured informal interviews with TRE participants throughout the intervention and semi-structured in-depth interviews (IDIs) with a subset (n = 19) at 12 months. IDIs and focus group discussions were conducted with healthcare staff. Results: Implementation faced significant contextual challenges, including high food insecurity, economic constraints, and high crime levels. Cultural norms around food hospitality also posed barriers. Despite this, TRE was highly feasible and acceptable. Participants reported positive behavioural changes, establishing eating routines and consuming healthier foods. Perceived health benefits included improved appetite control, wellbeing, sleep, and weight management. Key facilitators were the intervention’s flexibility and, importantly, the non-judgmental, empathetic support from fieldworkers, which drove engagement and retention. Healthcare workers expressed willingness to integrate TRE into existing HIV counsellor-led services, and nearly all participants desired to continue TRE post-intervention. Conclusions: This process evaluation demonstrates that TRE is a contextually suitable and acceptable intervention from an implementation perspective. Its success in practice, however, depends on mitigating complex multi-level barriers through a flexible program design and high-quality, relationship-focused support integrated into existing healthcare infrastructure. Trial registration: PACTR202302484999720, 8 February 2023.

Anorexia of ageing - the age-related reduction in appetite and food intake - is a public health concern for an ageing global population. However, current understanding of the aetiology of the condition is limited. In this review, evidence of gut hormone responses to feeding in older adults is reviewed, and it is proposed that a dysregulation of this process is a mechanism driving low appetite in later life. The evidence is synthesised to critically present this case, spotlighting recent data demonstrating a highly anorexigenic gut hormone profile in older adults exhibiting low appetite, which is not observed in older adults exhibiting a "healthy" appetite. These findings and this theory are interrogated with an appreciation that appetite control is complex and multifactorial, not least in the context of anorexia of ageing; it is posited that changes in gut hormone secretions are a mechanism rather than the mechanism, but propose that this may explain certain presentations of anorexia of ageing. The current knowledge base is contextualised for practical implications and priorities for future research are highlighted.

It is difficult to imagine that an individual living with obesity may gain body weight in response to a diet and physical activity program aiming at a negative energy balance. However, this type of case is a matter of usual occurrence in obesity clinics and has been traditionally explained by a lack of adherence to guidelines. While a link between adherence to a weight loss intervention and its outcome has been demonstrated, there is growing evidence showing that unsuccessful response to weight-reducing programs may happen in some individuals despite adequate adherence, be it imposed experimentally or spontaneously expressed in a free-living context. As described in this paper, the response to a weight loss program may range from a weight gain to a greater than expected weight loss. Based on our research findings and available literature, an unsuccessful body-weight response is seen in 5% to 20% of individuals and is attributable to behavioral and metabolic changes affecting appetite control and thermogenesis. Experimental evidence also shows that the response to a negative-energy balance is genetically determined. Globally, these observations emphasize the importance of future research in precision medicine to develop treatment approaches that progressively become more individualized.

Sleep is a vital biological function that directly influences metabolic regulation, hormonal balance, and energy homeostasis. Recent scientific evidence demonstrates that sleep duration and quality play a decisive role in physiological weight loss, affecting fat oxidation, appetite control, insulin sensitivity, and body composition. This paper presents the relationship between sleep and weight loss. Through an in-depth review of contemporary scientific literature and synthesis of experimental findings, the study highlights that insufficient or disrupted sleep significantly reduces fat loss efficiency while promoting hormonal dysregulation and lean mass loss. The results emphasize that sleep optimization should be considered a core component of evidence-based weight management strategies.

Background: Metabolic syndrome is a multifactorial condition characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, leading to increased cardiometabolic risk. Conventional therapies often show limited long-term success due to poor compliance. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, is emerging as a potential adjunct in managing obesity-related metabolic disorders by modulating neural circuits responsible for appetite and impulse control. Aims and Objectives: To evaluate the effect of high-frequency rTMS on anthropometric, behavioral, and biochemical parameters in obese individuals with metabolic syndrome. Materials and Methods: This randomized, single-blind, sham-controlled trial included 30 obese adults divided equally into intervention (real rTMS) and control (sham) groups. The intervention group received 12 sessions of 10 Hz rTMS over the left dorsolateral prefrontal cortex for 4 weeks. Assessments were conducted at baseline, post-therapy, 15 days, and 30 days. Outcomes included body mass index (BMI), waist circumference (WC), body weight, food craving questionnaire-trait (FCQ-T) scores, fasting blood sugar, hemoglobin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), and serum cortisol. Data were analyzed using the Statistical Package for the Social Sciences v21, with P<0.05 considered significant. Results: rTMS produced significant reductions in BMI (−1.06±0.684 kg/m2), WC (−1.59±1.140 cm), body weight (−2.98±1.731 kg), and FCQ-T scores (−14.13±8.927) over 30 days (P=0.001). Triglycerides and hs-CRP decreased significantly, while high-density lipoprotein cholesterol showed mild improvement. Glycemic parameters showed marginal, non-significant changes. Conclusion: High-frequency rTMS is a safe and effective non-pharmacological adjunct that improves obesity-related anthropometric and behavioral outcomes and exerts favorable metabolic effects in patients with metabolic syndrome.

Weight gain can be a concern for some women, with some considering a body conforming to specific beauty standards as an ideal or desired goal. The use of progesterone hormone injections, which affect the appetite control center in the hypothalamus, can increase appetite and potentially lead to weight gain. This research employs a descriptive-analytical method with a quantitative approach conducted at the Independent Midwife Practice in the working area of the Kragilan Serang Community Health Center, Banten, using secondary data from medical records. Data collection involved 96 respondents divided into 48 samples of 1-month injectable contraceptive (KB Suntik) users and 48 samples of 3-month injectable contraceptive users. The total research sample size is 96 respondents, with the majority falling in the 20–40 age group and the remainder aged >40 years. The results indicate that among the 48 respondents using the 1-month injectable contraceptive, the average weight gain is 0. 938 kg, while for the 3-month injectable contraceptive, the average weight gain is 4. 251 kg.

This review aims to (1) provide an overview of research investigating the relationship between body composition, specifically fat-free mass (FFM) and fat mass (FM), appetite and energy intake (EI) and (2) to investigate potential mechanisms underlying these relationships, with a focus on ageing. Appetite and EI are influenced by complex, multifactorial pathways involving physiological, psychological, environmental, social and cultural factors. Early research investigating the association of body composition with appetite and EI focused on FM; however, the role of FFM in appetite control is gaining increasing attention. Studies have shown that FFM is positively associated with EI in younger populations, including infants, adolescents and adults. In contrast, FM appears to have no association or a weak inverse association with appetite/EI. However, research in older adults is limited, and the underlying mechanisms are not fully understood. It has been suggested that one way in which FFM may influence appetite and EI is by impacting resting metabolic rate (RMR). FFM, which includes metabolically active tissues including skeletal muscle and organs, represents the largest determinant of RMR and therefore may influence appetite and EI by ensuring the energetic requirements of crucial tissue-organs and metabolic processes are reached. Given that declines in FFM and RMR are common with ageing, they may be possible targets for interventions aimed at improving appetite and EI. While current evidence in older adults supports a positive association between FFM and appetite, further longitudinal studies are needed to explore this relationship in different contexts, along with the underlying mechanisms.

Obesity management medications influence eating behavior and promote substantial weight reduction in individuals with obesity or overweight. Existing patient-reported outcome measures do not adequately measure appetite and eating behavior concepts relevant to individuals with these conditions. This study presents psychometric properties of the Eating Behavior and Appetite Questionnaire (EBAQ), a new patient-reported outcome measure to assess appetite and eating behaviors in adults with obesity or overweight. Participants (n=120) completed two web-based surveys (baseline, week 2). Survey 1 included the 21-item EBAQ, Control of Eating Questionnaire, Food Cravings Questionnaire-Trait-reduced, Impact of Weight on Quality of Life-Lite Clinical Trials Version, and Patient Global Impression of Severity (PGIS) items for appetite, eating control, cravings, and overall eating behavior. Survey 2 included the EBAQ and PGIS items. Factor structure, reliability, and validity of the EBAQ were assessed. Exploratory factor analysis of the EBAQ supported a 2-factor structure. Items loaded moderately to strongly (≥0.48) on factors corresponding to appetite control or eating behavior (inter-factor correlation 0.57). Four items with factor loadings≤0.43 were dropped. Internal consistency for the 17-item EBAQ was good/excellent for the domain scores (0.84-0.91) and excellent for the total score (0.92). Test-retest reliability was good (intraclass correlation coefficients≥0.84). Convergent validity was demonstrated via large correlations with the Control of Eating Questionnaire craving subscales, Food Cravings Questionnaire-Trait-reduced total score, and PGIS items, and smaller correlations with less similar PRO measures. EBAQ domain and total scores demonstrated known-groups validity, with higher EBAQ scores in participants who reported a well-controlled appetite, feeling in control of their eating, fewer food cravings, and better eating habits (i.e., higher PGIS scores). Results support the 2-factor structure, reliability, and validity of the final 17-item EBAQ. The EBAQ can be used in observational studies, clinical trials, and clinical practice to comprehensively assess appetite and eating behaviors in individuals with obesity or overweight.

Effects of commercial genetic selection on gene expression in the developing neuroendocrine system of broilers

Investigation of cholecystokinin-8s-induced hypophagia in neonatal broiler chicks: Roles of central adrenergic and serotonergic systems

Dietary fiber is a key human nutritional component with multiple overall health benefits, especially for preventing chronic diseases like type 2 diabetes, cardiovascular diseases, obesity and colorectal cancer. Despite decades of research confirming its importance, many reviews fail to link its chemical properties to in vivo mechanisms and public health roles. This paper integrates these by summarizing its chemical composition, physical properties, classification and associating them with health-effect nutritional mechanisms. The results of this paper show that dietary fiber acts via multiple pathways. It regulates blood glucose and cholesterol, improves gut health, aids appetite control and reduces inflammation. Soluble fibers with high viscosity and fermentability, such as β-glucan and pectin, are most effective for better metabolic outcomes. However, global intake is far below the WHO’s 25-30g daily recommendation. This gap highlights the need for nutrition education, improved food labeling and fiber-fortified foods. Future research should optimize fiber classification beyond “soluble vs. insoluble” and explore personalized nutrition to enhance its chronic disease prevention effects.

The gut-brain axis is a bidirectional communication network in which gut microbiota and their metabolites influence central nervous system (CNS) function. Among these metabolites, bile acids have emerged as key signaling molecules that modulate metabolic and neuroendocrine pathways. Microbiota-mediated modifications of bile acid composition affect receptors such as farnesoid X receptor (FXR)and Takeda G protein-coupled receptor 5 (TGR5), thereby influencing neuronal activity, appetite control, glucose metabolism, and energy balance. Emerging evidence indicates that bile acids act both directly on the CNS and indirectly via endocrine and immune mediators, linking microbial metabolism to brain function. By integrating microbiological, metabolic, and neuroendocrine perspectives, bile acids can be viewed as critical messengers in the communication between the gut microbiota and the CNS. The purpose of this review is thus to synthesize current mechanisms underlying these interactions and highlight their therapeutic potential in metabolic and neurodegenerative disorders.

The central melanocortin system links nutrition to energy expenditure. Melanocortin-4 receptor (MC4R) controls appetite and food intake, and its signaling is potentiated by melanocortin-2 receptor accessory protein 2 (MRAP2). Human mutations in MC4R and MRAP2 are associated with obesity. Here, we sought to determine whether MRAP2 affected the activity of MC3R, which is structurally similar to MC4R and which regulates sexual maturation, linear growth rate, and lean mass accumulation. Single-molecule pull-down assays showed that MC3R and MRAP2 interacted in HEK293 cells. Analysis of fluorescence photobleaching steps showed that MC3R and MRAP2 readily formed heterodimers, most commonly with a 1:1 stoichiometry. Mining of previously published human single-nucleus and spatial transcriptomic data showed coexpression of MRAP2 and MC3R in hypothalamic neurons that function in energy homeostasis and appetite control. In HEK293 cells, MRAP2 enhanced cAMP signaling downstream of MC3R, impaired β-arrestin recruitment to MC3R, and reduced MC3R internalization. The ability of MRAP2 to promote MC3R signaling was suppressed by alanine mutagenesis of five MRAP2 and two MC3R transmembrane residues identified by structural homology models as important for the interaction. We showed that variants of MRAP2 found in individuals who are overweight or obese did not enhance MC3R-driven signaling. Thus, these studies implicate MRAP2 as an important regulator of MC3R function and provide further evidence for the crucial role of MRAP2 in energy homeostasis.