Search Results (354)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the liver fat content in patients with obesity and T2D. However, its effect on liver-specific outcomes such as steatosis and fibrosis remains incompletely characterized. Low-energy ketogenic therapy (LEKT), a nutritional strategy characterized by carbohydrate restriction and nutritional ketosis, may enhance hepatic β-oxidation and reduce hepatic lipogenesis. To date, however, the combination of TZP and LEKT has not been studied in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the hepatic and metabolic effects of TZP combined with either LEKT or a conventional low-calorie diet (LCD) over a 12-week period. Methods: Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group. As primary endpoints, the controlled attenuation parameter (CAP, an index of hepatic steatosis) and liver stiffness measurement (LSM, an index of liver fibrosis) were assessed at the baseline and after 12 weeks using FibroScan^®. Secondary outcomes included changes in body mass index (BMI), glycated hemoglobin (HbA1c), and liver enzymes. Adherence to both diet and pharmacological treatment, as well as tolerability, were systematically monitored throughout the intervention period. Results: Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665). CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP −12.5%, p < 0.001; LSM −22.7%, p < 0.001) versus LCD (CAP −6.7%, p = 0.014; LSM −9.2%, p = 0.022). Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03). Conclusions: Based on these preliminary findings, we support the hypothesis that the combination of TZP and LEKT may be superior to TZP with an LCD in reducing hepatic steatosis and stiffness in individuals with obesity. Full article

Background/Objectives: Daily caloric restriction (DCR) is a common dietary weight loss strategy, but leads to metabolic and behavioral adaptations, including maladaptive eating behaviors and dysregulated appetite. Intermittent fasting (IMF) may mitigate these effects by offering diet flexibility during energy restriction. This secondary analysis compared changes in eating behaviors and appetite-related hormones between 4:3 intermittent fasting (4:3 IMF) and DCR and examined their association with weight loss over 12 months. Methods: Adults with overweight or obesity were randomized to 4:3 IMF or DCR for 12 months. Both randomized groups received a matched targeted weekly dietary energy deficit (34%), comprehensive group-based behavioral support, and a prescription to increase moderate-intensity aerobic activity to 300 min/week. Eating behaviors were assessed using validated questionnaires at baseline and months 3, 6, and 12. Fasting levels of leptin, ghrelin, peptide YY, brain-derived neurotrophic factor, and adiponectin were measured at baseline and months 6 and 12. Linear mixed models and Pearson correlations were used to evaluate outcomes. Results: Included in this analysis were 165 adults (mean ± SD; age 42 ± 9 years, BMI 34.2 ± 4.3 kg/m², 74% female) randomized to 4:3 IMF (n = 84) or DCR (n = 81). At 12 months, binge eating and uncontrolled eating scores decreased in 4:3 IMF but increased in DCR (p < 0.01 for between-group differences). Among 4:3 IMF, greater weight loss was associated with decreased uncontrolled eating (r = −0.27, p = 0.03), emotional eating (r = −0.37, p < 0.01), and increased cognitive restraint (r = 0.35, p < 0.01) at 12 months. There were no between-group differences in changes in fasting appetite-related hormones at any time point. Conclusions: Compared to DCR, 4:3 IMF exhibited improved binge eating and uncontrolled eating behaviors at 12 months. This may, in part, explain the greater weight loss achieved by 4:3 IMF versus DCR. Future studies should examine mechanisms underlying eating behavior changes with 4:3 IMF and their long-term sustainability. Full article

Background: The gut microbiota is increasingly recognized as a key modulator in obesity management, influencing host energy balance, lipid metabolism, and inflammatory pathways. With obesity prevalence continuing to rise globally, dietary interventions that promote beneficial microbial shifts are essential for enhancing weight loss outcomes and long-term health. Objective: This study investigated the effects of the multicomponent Weight Loss Maintenance 3 Phases Program (WLM3P), which integrates caloric restriction, a high-protein low-carbohydrate diet, time-restricted eating (10h TRE), dietary supplementation (prebiotics and phytochemicals), and digital app-based support on gut microbiota composition compared to a standard low-carbohydrate diet (LCD) in adults with obesity. The analysis focused exclusively on the 6-month weight loss period corresponding to Phases 1 and 2 of the WLM3P intervention. Methods: In this sub-analysis of a randomized controlled trial (ClinicalTrials.gov Identifier: NCT04192357), 58 adults with obesity (BMI 30.0–39.9 kg/m²) were randomized to the WLM3P (n = 29) or LCD (n = 29) groups. Stool samples were collected at baseline and 6 months for 16S rRNA sequencing. Alpha and beta diversity were assessed, and genus-level differential abundance was determined using EdgeR and LEfSe. Associations between microbial taxa and clinical outcomes were evaluated using regression models. Results: After 6-month, the WLM3P group showed a significant increase in alpha diversity (p = 0.03) and a significant change in beta diversity (p < 0.01), while no significant changes were observed in the LCD group. Differential abundance analysis revealed specific microbial signatures in WLM3P participants, including increased levels of Faecalibacterium. Notably, higher Faecalibacterium abundance was associated with greater reductions in fat mass (kg, %) and visceral adiposity (cm²) in the WLM3P group compared to LCD (p < 0.01). Conclusions: These findings suggest a potential microbiota-mediated mechanism in weight loss, where Faecalibacterium may enhance fat reduction effectiveness in the context of the WLM3P intervention. Full article

Background/Objectives: Proper management of food services aimed at preventing malnutrition and weight loss among residents of long-term care facilities is a critical priority. Accordingly, accurate prediction of energy intake requirements is necessary. This study aimed to estimate the energy intake required to prevent weight loss in residents of Japanese long-term care facilities. Methods: Body weight and 12-day dietary intake were measured from residents aged ≥75 years with a body mass index (BMI) < 25.0 kg/m² who were consuming a regular or chopped diet. In the survey, individuals with oral intake were included, while those with swallowing problems, serious illnesses, dietary restrictions, or medications causing appetite loss were excluded. The rate of body-weight loss and the energy intake per kilogram of body weight (kcal/kg BW) during each 6-month period were calculated. The energy intake per kilogram of body weight corresponding to the rate of body-weight loss of 0% was estimated from the regression line between the rate of body-weight loss and energy intake per kilogram of body weight. Results: The data was analyzed for 99 residents (15 men and 84 women, age 89.3 ± 5.0 years, BMI 20.3 ± 2.6 kg/m²). From the regression results in all participants, the energy intake per kilogram of body weight corresponding to the rate of body-weight loss of 0% was 31.4 kcal/kg BW overall and 33.4 kcal/kg BW for those with a BMI < 18.5 kg/m². Conclusions: The calculation of energy intake using a regression line may be able to predict the energy intake required for weight maintenance without using instrumental measurements or estimation equations, especially in the case of underweight individuals. Full article

Next to adrenergic signalling, purinergic pathways mediated by extracellular adenine nucleotides have been described to shape thermogenic and metabolic functions in brown adipose tissue (BAT). Here we describe high expression of P2X5 that is activated by ATP in mature adipocytes of BAT and differentiated brown adipocytes in vitro. The levels of other P2X family members were much lower, or expression was restricted to tissue-resident macrophages or endothelial cells. Global and brown adipocyte-specific P2rx5 deficiency resulted in lower expression of the uncoupling protein 1 (UCP1). However, indirect calorimetry studies showed that P2X5 did not affect systemic energy expenditure. Of note, glucose tolerance was impaired under chow and obesogenic high-fat diet conditions, which can be explained by lower glucose disposal into BAT but not into other organs. In summary, these data indicate a modulatory role of P2X5 in systemic and BAT-specific glucose metabolism. Full article

Background/Objectives: More children and adolescents are adopting vegetarian diets. A balanced diet is particularly important for growth and bone development in children. It is important to clarify whether a vegetarian diet affects these processes. A systematic literature review was conducted to identify studies investigating differences in anthropometric data, nutrient intake, and biomarkers between vegetarian and omnivorous children. Methods: PUBMED, MEDLINE, and Web of Science Core Collections were searched between the end of 2014 and 2023. We included peer-reviewed randomized controlled trials, intervention, or observational studies that were published in English or German and investigated the differences between healthy children and adolescents from high-income countries who consumed either a vegetarian or an omnivorous diet. The review was conducted in accordance with the PRISMA guidelines. If at least five values with the same unit were available from different studies, a cumulative analysis of selected parameters was conducted. Due to the participants’ varying ages across the studies, limited cumulative analyses were conducted additionally by age category. Results: A total of 1681 studies were screened, of which 20 met the inclusion criteria. Significant differences were found in fiber and energy intake from carbohydrates and proteins. The results were strengthened by the restricted cumulative analysis of the 2–10 age category, which also revealed significant differences when comparing VG and OM. Conclusions: A higher intake of fiber, more energy from carbohydrates, and sufficient energy from proteins and less from fat can be regarded as the benefits of a vegetarian diet, according to this review. There are also the first indications of enhanced vitamin C and E, iron, folate, and magnesium intake. These characteristics can be regarded as potential benefits of a vegetarian diet. A lower vitamin B12 and vitamin D intake has been identified as a potential risk factor. Further longitudinal, prospective, observational studies are needed. Prospero registration date and number: 6 March 2023, CRD42023402301. Full article

Obesity and metabolic disorders remain major global health concerns, traditionally attributed to excessive caloric intake and poor diet quality. Recent studies emphasize that the timing of meals plays a crucial role in determining metabolic health. This review explores chrononutrition, a growing field that examines how food intake patterns interact with endogenous circadian rhythms to influence energy balance, glucose and lipid metabolism, and cardiometabolic risk. The circadian system, which includes a central clock in the suprachiasmatic nucleus and peripheral clocks in metabolic tissues, regulates physiological functions on a 24 h cycle. While light entrains the central clock, feeding schedules act as key synchronizers for peripheral clocks. Disrupting this alignment—common in modern lifestyles involving shift work or late-night eating—can impair hormonal rhythms, reduce insulin sensitivity, and promote adiposity. Evidence from clinical and preclinical studies suggests that early time-restricted eating, where food intake is confined to the morning or early afternoon, offers significant benefits for weight control, glycemic regulation, lipid profiles, and mitochondrial efficiency, even in the absence of caloric restriction. These effects are particularly relevant for populations vulnerable to circadian disruption, such as adolescents, older adults, and night-shift workers. In conclusion, aligning food intake with circadian biology represents a promising, low-cost, and modifiable strategy to improve metabolic outcomes. Integrating chrononutrition into clinical and public health strategies may enhance dietary adherence and treatment efficacy. Future large-scale studies are needed to define optimal eating windows, assess long-term sustainability, and establish population-specific chrononutritional guidelines. Full article

Background/Objectives: N-lactoyl-phenylalanine (Lac-Phe), an exercise-induced metabolite, has been shown to reduce food intake, decrease body weight and adiposity, and improve glucose homeostasis without affecting energy expenditure. Until now, Lac-Phe has mainly been investigated in blood plasma, showing its appetite-suppressing effects. Interestingly, these beneficial effects were caused by a temporary increase in Lac-Phe levels after exercise. Second, despite the central role of the central nervous system in the homeostatic control of energy metabolism, little is known about the presence and function of Lac-Phe in the brain. The goal of this study is to investigate how Lac-Phe concentrations in the brain change during the 24 h light/dark cycle. Methods: We conducted an experiment in rats in which time-restricted running was combined with time-restricted feeding (TRF) of a high-calorie diet, after which Lac-Phe levels were measured in the hypothalamus and cortex using stable isotope dilution LC-MS/MS. Microglia were isolated from rat brains to study Lac-Phe-related gene expression. Results: We found that Lac-Phe levels changed over time within the 24 h light/dark cycle in the hypothalamus and/or cortex, even without exercise. Our study indicates that brain Lac-Phe is not only induced by exercise but also by high-calorie diet intake independent of exercise. Finally, we showed that microglial cells are cytosolic nonspecific dipeptidase 2 (CNDP2) positive and therefore able to produce Lac-Phe. Hereby, we identified SLC16A1 in microglia as a possible key mediator of Lac-Phe production. Conclusions: We conclude that high-calorie diet consumption induces Lac-Phe changes in the brain in a time-of-day manner independent of exercise. This study provides new knowledge on the presence and production of Lac-Phe in the brain. Further research is needed to elucidate the potential mechanism by which Lac-Phe reduces food intake and body weight by targeting appetite-suppressing neurons. Full article

β-hydroxybutyrate (BHB) serves as an alternative cellular fuel during states of low glucose availability, such as fasting or carbohydrate restriction, when the body shifts to using fats and ketone bodies for energy. While BHB has shown potential metabolic benefits, its mechanisms of action in the context of obesity are not fully understood. In this study, we examined the effects of BHB supplementation on subcutaneous adipose tissue (SAT) metabolism in a diet-induced obesity (DIO) mouse model. Adult male mice were first fed a high-fat diet for six weeks, followed by a standard diet with or without BHB supplementation for an additional six weeks. BHB supplementation led to significant body weight loss independent of food intake. This weight reduction was associated with decreased adipocyte differentiation, reflected by reduced peroxisome proliferator-activated receptor gamma (PPARγ) protein levels and lower uncoupling protein 1 (UCP1) expression, indicating altered SAT function. Transcriptomic analysis of SAT revealed upregulation of genes involved in fatty acid activation and transport (e.g., Slc27a2, Plin5, Acot4, Acsm3, Rik). Functional enrichment highlighted the activation of the PPAR signaling pathway and enrichment of peroxisomal components in the BHB group. Together, these results suggest that BHB promotes lipid remodeling in SAT, enhancing fatty acid metabolism while suppressing thermogenic pathways, and thus may represent a novel mechanism contributing to adiposity reduction and metabolic improvement. Full article

Background: Dietary consumption of insulinogenic amino acids (IAA) is known to contribute to the development of insulin resistance. It remains to be studied whether dietary IAA restriction improves glucose metabolism and insulin sensitivity and whether this improvement is related to alterations in glucose metabolism in peripheral tissues. The objective of this study was to examine the effect of IAA restriction on glucose metabolism in a piglet model. Methods: Following the acclimation period, thirty-two seven-day-old male piglets were randomly assigned into one of three groups for three weeks as follows (n = 10–11/group): (1) NR (control): basal diet without IAA restriction; (2) R50: basal diet with IAA restricted by 50%; (3) R75: basal diet with IAA restricted by 75%. IAA were alanine (Ala), arginine (Arg), isoleucine (Ile), leucine (Leu), lysine (Lys), threonine (Thr), phenylalanine (Phe), and valine (Val) as suggested by previous studies. Thermal images, body weight, and growth parameters were recorded weekly, oral glucose tolerance tests were performed on week 2 of the study, and blood and tissue samples were collected on week 3 after a meal test. Results: R75 improved glucose tolerance and, together with R50, reduced blood insulin concentration and homeostatic model assessment for insulin resistance (HOMA-IR) value, which is suggestive of improved insulin sensitivity following IAA restriction. R75 increased thermal radiation and decreased adipocyte number in white adipose tissue (WAT). R75 had a greater transcript of glucose transporter 1 (GLUT1), phosphofructokinase, liver type (PFKL), and pyruvate kinase, liver, and RBC (PKLR) in the liver and glucokinase (GCK) in WAT indicating a higher uptake of glucose in the liver and greater glycolysis in both liver and WAT. R75 increased the mRNA abundance of insulin receptor substrate 1 (IRS1) and protein kinase B (AKT1) in skeletal muscle suggestive of enhanced insulin signaling. Further, R75 had a higher mRNA of fibroblast growth factor 21 (FGF-21) in both the liver and hypothalamus and its upstream molecules such as activating transcription factor 4 (ATF4) and inhibin subunit beta E (INHBE) which may contribute to increased energy expenditure and improved glucose tolerance during IAA restriction. Conclusions: IAA restriction improves glucose tolerance and insulin sensitivity in piglets while not reducing body weight, likely through improved hepatic glycolysis and insulin signaling in skeletal muscle, and induced FGF-21 signaling in both the liver and hypothalamus. Full article

Over the years, caloric intake has remained a subject of profound scrutiny. Within the scientific community, there has been rigorous debate to ascertain which path is most ideal for enhancing quality of life and extending the human lifespan. Caloric restriction has been shown to be a promising contributor towards longevity and delaying the onset of age-related diseases. This diet consists of a reduction in caloric intake while maintaining essential energy and nutritional requirements to achieve optimal health while avoiding malnutrition. However, the effects of this nutritional regimen on male reproductive health have not yet been comprehensively studied. Nevertheless, such a complex process will certainly be regulated by a variety of metabolic sensors, likely sirtuins. Evidence has been gathered regarding this group of enzymes, and their ability to regulate processes such as chromatin condensation, the cell cycle, insulin signaling, and glucose and lipid metabolism, among many others. Concerning testicular function and male fertility, sirtuins can modulate certain metabolic processes through their interaction with the hypothalamic–pituitary–gonadal axis and mitochondrial dynamics, among many others, which remain largely unexplored. This review explores the impact of caloric restriction on male fertility, highlighting the emerging role of sirtuins as key regulators of male reproductive health through their influence on cellular metabolism. Full article

Obesity (OB) has become a serious health issue owing to its ever-increasing prevalence over the past few decades due to its contribution to severe metabolic and inflammatory disorders such as cardiovascular disease, type 2 diabetes, and cancer. The unbalanced energy metabolism in OB is associated with substantial epigenetic changes mediated by the gut microbiome (GM) structure and composition alterations. Remarkably, experimental evidence also indicates that OB-induced epigenetic modifications in adipocytes can lead to cellular “memory” alterations, predisposing individuals to weight regain after caloric restriction and subsequently inducing inflammatory pathways in the liver. Various environmental factors, especially diet, play key roles in the progression or prevention of OB and OB-related disorders by modulating the GM structure and composition and affecting epigenetic mechanisms. Here, we will first focus on the key role of epigenetic aberrations in the development of OB. Then, we discuss the association between abnormal alterations in the composition of the microbiome and OB and the interplays between the microbiome and the epigenome in the development of OB. Finally, we review promising strategies, including prebiotics, probiotics, a methyl-rich diet, polyphenols, and herbal foods for the prevention and/or treatment of OB via modulating the GM and their metabolites influencing the epigenome. Full article

Background: Calorie restriction is increasingly recognized as a strategy for glycemic management in type 2 diabetes mellitus (DM) by promoting weight loss and potentially achieving diabetes remission. This study evaluated the feasibility of a 12-week structured calorie-restricted dietary intervention based on healthy Korean dietary patterns for adults with early type 2 DM. Methods: Adults aged 18–60 years with a body mass index (BMI) greater than 25 kg/m² and a short duration of diabetes were recruited. The intervention comprised two phases: a 6-week weight loss phase, targeting a 3% reduction every two weeks, starting with an 800 kcal/day diet and increasing by 200 kcal per phase, with all meals provided via home delivery, followed by a 6-week self-managed weight maintenance period, preceded by a one-week reintroduction phase with meals provided. Results: Among 27 participants, 24 completed the intervention (89% retention). Mean weight reduction at 6 weeks was 6.4 kg (7.6%), primarily achieved during Phase 1 (5.1%). By 12 weeks, the average weight reduction further improved to 7.4 kg (8.7%). Dietary adherence ranged from 80% to 90%, with energy intake closely aligning with the prescribed targets. Non-achievers exhibited a smaller initial reduction (2.5 kg vs. 3.9 kg), with the gap persisting throughout the study. Postprandial glycemic response to a mixed meal (65% carbohydrate) significantly improved from baseline to week 5. Conclusions: This structured dietary intervention demonstrated substantial weight reduction and improved glycemic response in adults with type 2 DM, highlighting its feasibility and effectiveness as a guided strategy for weight management. Full article

Background: This randomized controlled study sought to determine the effect of intermittent fasting on anthropometric measurements, fibroblast growth factor (FGF)-21, and autophagy markers, as well as on hepatic steatosis and fibrosis levels in overweight or obese patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: Patients were randomly assigned into two groups: received a dietary treatment involving 22–25 kcal/kg/day of energy for 8 weeks and followed the same dietary intervention and a 16:8 pattern. The extent of hepatic steatosis and fibrosis was determined using transient elastography on a FibroScan^® device. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), determined by transient elastography, reflect hepatic steatosis and fibrosis, respectively. In duplicate, serum levels of FGF-21, Beclin-1, and ATG-5 were determined using enzyme-linked immunosorbent assay. Results: The study included 48 patients with a mean age of 48.2 ± 1.4 years (27 female and 21 male). Improvements in anthropometric measurement and CAP and LSM levels and a decrease in serum FGF-21 levels were found in both groups (p < 0.05). Changes in the CAP and FGF-21 levels were higher in the energy + time-restricted diet group (p < 0.05). Autophagy-related protein (ATG)-5 levels increased only in the energy + time-restricted diet group [(0.74 (0.46–1.29) ng/mL vs. 0.95 (0.73–1.32) ng/mL, p = 0.03]. Conclusions: Intermittent fasting was potentially practical in the management of MAFLD. In particular, changes in FGF-21 and ATG-5 levels indicate the potential of intermittent fasting to regulate metabolic processes and autophagy. However, methodological limitations should be taken into consideration when interpreting the study results. Full article

Background: Sarcopenia is characterized by a loss of muscle mass, strength, and function. At present, there are no effective methods available for prevention or treatment. Oxidative Balance Score (OBS) has been shown to be significantly correlated with a decreased risk of sarcopenia. Nevertheless, gender-specific studies still exhibit certain limitations. Methods: Individuals who completed dual-energy X-ray absorptiometry and the diet and lifestyle questionnaires from the National Health and Nutrition Examination Survey were enrolled. OBSs were calculated according to dietary or lifestyle variables and physical activity. Sarcopenia with low muscle mass (SLM) was identified based on the ratio of appendicular skeletal muscle mass to body mass index. A logistic regression analysis investigated the association between OBS and the risk of SLM in different gender groups. Kaplan–Meier survival and subgroup analyses and Cox regression analyses were used to explore the relationship between OBS and mortality in individuals with SLM in each gender subgroup. Results: The level of OBS in the SLM group was lower (20.40 vs. 17.07, p < 0.05). A multivariate logistic regression analysis showed that the OR between individual dietary nutrients and lifestyle and the risk of SLM exhibition was gender-specific. Stratified analyses revealed that total OBS, as well as diet and lifestyle OBS were negatively associated with the risk of SLM within each gender subgroup (all p < 0.05, all trends p < 0.05). Furthermore, a restriction cubic spline regression analysis showed that diet and lifestyle OBSs were negatively correlated with the risk of SLM in females (nonlinear p = 0.0469, nonlinear p = 0.0254). The KM curve showed that OBS was not significantly associated with all-cause mortality in the male and female subgroups (female, p = 0.064, male, p = 0.53). Conclusions: This study establishes a significant negative correlation between OBS and the risk of SLM, particularly among females. Consequently, adopting an antioxidant diet and lifestyle may prove to be more advantageous for females. Full article