Search Results (329)

Background/Objectives: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects—particularly those involving Orexin-A, a peptide implicated in energy regulation—remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. Methods: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m²) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. Results: All participants completed the intervention. The ketogenic diet produced the largest sustained reductions in BMI, fat mass, fasting glucose, and total cholesterol over 12 months. TRF16:8 elicited more rapid early metabolic improvements and showed the most consistent longitudinal increase in Orexin-A levels. The ADF5:2 protocol resulted in moderate improvements across outcomes. In all groups, increases in Orexin-A were associated with markers of improved metabolic flexibility and reduced inflammation; however, mediation analyses were exploratory and non-causal. Between-group differences remained significant for fat mass, glucose, and Orexin-A trajectories after correction for multiple comparisons. Conclusions: The ketogenic diet was associated with the most pronounced long-term metabolic improvements, whereas 16:8 time-restricted eating yielded faster early responses and the most stable enhancement in Orexin-A levels. These findings indicate distinct metabolic and neuroendocrine adaptation profiles across dietary strategies. Given the small sample size, results should be interpreted cautiously, and larger trials are warranted to clarify the role of Orexin-A as a potential biomarker of dietary response in obesity. Full article

Background/Objectives: Sex-specific differences in metabolic dysfunction-associated fatty liver disease (MAFLD)-related hepatocellular carcinoma (HCC) remain poorly understood. This study aimed to clarify sex-associated disparities in disease progression and recovery using a diethylnitrosamine (DEN) plus Western diet/fructose-induced murine model combined with artificial intelligence (AI)-assisted histological analysis. Methods: Male and female C57BL/6J mice received a single diethylnitrosamine injection and were fed a Western diet/fructose regimen for 38 weeks, followed by an 8-week recovery period on standard chow. Serum biochemical parameters were measured, and liver histology was assessed using second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy. Steatosis and fibrosis were quantified within tumor and adjacent non-tumor regions using AI-based image analysis. Results: Male mice developed more severe disease phenotypes, including greater tumor burden and higher serum alanine aminotransferase levels, compared with females. Following dietary recovery, female mice showed substantial reductions in tumor number and hepatic steatosis, particularly in non-tumor regions; in contrast, male mice demonstrated only minimal improvement. AI-assisted quantification confirmed considerable regression of both steatosis and fibrosis in females and moderate fibrosis improvement in both sexes. Conclusions: These findings indicate sexual dimorphism in the progression and regression of MAFLD-related HCC, with females exhibiting enhanced metabolic and histological recovery. The results underscore the importance of considering sex as a biological variable in preclinical metabolic dysfunction–associated fatty liver disease-related hepatocellular carcinoma research and highlight the value of AI-enhanced imaging for precise, objective evaluation of liver histology. Full article

Domesticated cats have evolved from the obligate carnivore Felis silvestris. The instinct to eat small frequent meals and a crepuscular feeding rhythm was conserved during domestication. Declining senses, cognitive impairment, and poor oral health decrease food intake in aging cats. Combined with metabolic and physiological changes, they are at risk of sarcopenia and general body condition impairment. Aging cats may, therefore, benefit from modified nutritional strategies to achieve their metabolic energy requirements; however, little is known about feeding patterns in aging cats and influence of food format. This in-home study of 134 aging cats (≥7 years) assessed ad libitum dry, wet, and wet/dry (‘mixed’) feeding regimens to compare 24 h feeding frequency and caloric intakes. Feeding frequency was significantly different between wet and dry (p = 0.02) and mixed and dry diets (p < 0.001), with cats consuming 6.0 (dry), 6.9 (wet), or 7.2 meals (mixed) per day. Mean caloric intakes were significantly higher for dry (262.6 kcal/d) and mixed (222.6 kcal/d) regimens (both p < 0.001) versus wet (138.1 kcal/d). In conclusion, healthy aging cats eat small frequent meals, with feeding frequency and caloric intake influenced by dietary format. These findings support development of evidence-based feeding guidelines for aging cats. Full article

The mass rearing of natural enemy insects is a cornerstone of effective green pest control, making the development of optimized artificial diets critical for sustaining large populations. However, existing artificial diets often have limitations, including inhibitory effects on the reproductive development of natural enemies. In this study, we innovatively incorporated 20% catalpol into the artificial diets for Harmonia axyridis, aiming to comprehensively assess the effects of such dietary regimens on larval development, reproductive performance, and the regulation of energy metabolism in H. axyridis. Our results demonstrated that catalpol supplementation significantly shortened the duration of the 4th instar larval and pupal stages and increased pupal weight. Furthermore, catalpol treatment enhanced reproductive capacity, as evidenced by increased fecundity, improved hatching rate stability, and enhanced ovarian development. This effect was directly correlated with the significant upregulation of the vitellogenin genes Vg1 and Vg2 and their receptor gene VgR at 3 days post-emergence. Regarding energy metabolism, catalpol supplementation led to increased glycogen reserves and glucose content. The expression of the membrane-bound trehalase enzyme gene TRE2 was significantly higher than that in the control group, and the expression level of the soluble trehalase enzyme gene TRE1 also showed a significant increase. These findings indicate that catalpol effectively optimized energy metabolism, thereby accelerating developmental processes and enhancing reproductive capacity. In this study, we elucidated the mechanism by which catalpol regulates physiological metabolism in predatory natural enemy insects. For the first time, catalpol was incorporated into the artificial diet of H. axyridis as a synergistic component, significantly enhancing its growth, reproductive capacity, and energy metabolism. These findings provide a scientific basis for developing efficient artificial feeding systems and improving the field adaptability of natural enemy insects. Full article

Natural products are a valuable source of bioactive compounds with established roles in oncology. Their structural diversity and ability to target multiple cancer-related pathways make them promising candidates for anticancer drug development. Increasing preclinical and clinical data highlight their potential not only to exert direct antitumor effects but also to enhance patient tolerance to conventional therapies by reducing side effects and improving treatment adherence. The Mediterranean region, known for its biodiversity and traditional dietary habits, provides a rich array of natural compounds with documented health benefits. Key Mediterranean natural plant products (MNPPs), including bioactives from olive oil, onion, citrus fruits, chili pepper and grapes, exhibit antioxidant, anti-inflammatory, and anti-proliferative properties. This review focuses on the molecular mechanisms of selected MNPPs, such as polyphenols, flavonoids, alkaloids, terpenes, organosulfur and furanocoumarin compounds, which modulate oxidative stress, inflammation, apoptosis, and tumor progression. Evidence from in vitro and in vivo studies supports their role in cancer prevention and as adjuvants in therapy. While further clinical research is needed, these findings suggest that incorporating MNPPs into therapeutic regimens could offer low-toxicity, multi-targeted support in oncology, improving both outcomes and quality of life in cancer patients. Full article

Time-qualified dietary interventions, including time-restricted eating (TRE), intermittent fasting (IF), and periodic fasting-mimicking diets (FMDs), have emerged as strategies to improve metabolic health. While preclinical studies consistently demonstrate robust effects on energy metabolism, cardiometabolic function, and longevity, translation to humans remains heterogeneous. In free-living settings, most metabolic improvements observed with TRE and IF appear primarily driven by spontaneous caloric restriction rather than meal timing per se, and isocaloric randomized controlled trials generally show no additional benefits compared to standard calorie restriction. Evidence supporting circadian-specific advantages, particularly for early TRE, is promising but inconsistent and often context-dependent. Important uncertainties also persist regarding long-term efficacy, lean mass preservation, safety in specific populations, and the physiological impact of extended fasting windows. Despite these controversies, time-qualified diets represent a paradigm shift in nutritional science by integrating chronobiology with dietary patterns. Future directions include tailoring eating windows to individual chronotypes, combining fasting regimens with high-quality dietary patterns and structured physical activity, and clarifying the molecular mechanisms that may mediate calorie-independent benefits. Large, long-term, mechanistically informed human trials are essential to determine whether aligning eating behaviors with circadian biology can produce durable clinical improvements. Such work will ultimately shape the role of personalized chrononutrition in preventive and therapeutic nutrition. Full article

Background/Objectives: Inborn errors of amino acid metabolism (IEAAMs) are inherited disorders caused by defects in amino acid catabolism, biosynthesis, or transport. In this review, we aimed to synthesise recent evidence on the clinical manifestations and current and future therapeutic strategies for major IEAAMs. Methods: A narrative review was undertaken on studies published up to November 2025. No fixed start date was set. Instead, earlier studies were included if historically significant or frequently cited in contemporary guidelines, and emphasis was placed on recent developments over the last 5–10 years. Evidence was identified through structured searches of PubMed, clinical trial registries, and public communications on selected IEAAMs, which were synthesised in textual and tabular form. Results: Management across IEAAMs involves the restriction of amino acids or natural proteins, disease-specific dietary formulations, micronutrient optimisation, cofactor or enzyme replacement, and pharmacological chaperones. This is supported by structured monitoring and emergency regimens to prevent catabolic crises. Organ transplantation remains crucial for select indications, such as liver transplantation in hereditary tyrosinaemia with liver disease. Novel approaches include substrate reduction, the pharmacological targeting of upstream pathways, viral vector gene transfer, and liver-directed mRNA therapy. Several of these novel approaches have entered clinical trials, but many remain in the preclinical stage. Conclusions: Despite advances in the treatment of IEAAMs, many patients still experience significant morbidity. Future focus should be on further refining emerging molecular and gene-based treatments and optimising neuroprotective and metabolic targets. The equitable implementation of personalised, life-spanning treatments within multidisciplinary rare disease services will be essential. Full article

This study examined how meal frequency under isocaloric conditions affects triglyceride accumulation in adipocytes, focusing on the role of insulin dynamics. Using a mathematical model of carbohydrate–lipid metabolism, we simulated feeding regimens from one to eight meals/day while holding calories and macronutrient ratios constant. A simplified model allowed independent variation in insulin peak amplitude, width, and overlap Results show that, relative to thrice-daily feeding (the reference regimen with stable triglyceride content over one month), infrequent meals (1–2/day) reduce, while frequent meals (5–8/day) increase triglyceride accumulation—most strongly in healthy individuals and attenuated in type 2 diabetes, as parameterized from the literature. Crucially, fat accumulation correlates not with average insulin levels but with its dynamic profile. Metabolic flux analysis revealed that triglyceride accumulation is driven not by changes in synthesis rate but by suppression of lipolysis, which depends on the amplitude, duration, and degree of overlap of insulin peaks. Thus, fat mass is shaped not only by caloric intake but by meal timing, which defines the insulin signal’s temporal structure. These findings highlight that insulin dynamics—not mean concentration—govern lipid metabolism, urging dietary guidelines to account for meal pattern, not just composition or total energy. Full article

Background: Obesity is a metabolic condition that may impair insulin sensitivity and disrupt glucose homeostasis. Since insulin and glucose affect insulin-like growth factor-1 (IGF-1), disruptions in this axis may elevate the risk of chronic diseases. Intermittent fasting (IF) modulates metabolic parameters, but the impacts on glucose regulation and IGF-1 remain underexplored. This study aimed to assess the short-term effects of two IF types, time-restricted feeding (TRF) and alternate-day modified fasting (ADMF), on fasting blood glucose (FBG) and IGF-1 in obese young women. Methods: A quasi-experimental pretest–posttest control group design was conducted over 20 days. The 31 subjects were allocated into ADMF (n = 10), TRF (n = 11), and Control (n = 10). After excluding dropouts and outliers, the final sample consisted of 22 subjects (ADMF = 7, TRF = 8, Control = 7). FBG and IGF-1 serum were measured pre- and post-intervention. Results: The FBG post-intervention significantly increased in TRF (p = 0.001) and ADMF (p = 0.036) groups, but not in Controls. Only the TRF group showed a significant reduction in IGF-1 levels (p < 0.001). Nevertheless, the ADMF group exhibited substantial decreases in body weight (p = 0.047) and visceral fat (p = 0.017). Conclusions: A 20-day IF in obese young women induced distinct metabolic effects: TRF lowered IGF-1, ADMF reduced adiposity, and both regimens increased FBG. These findings suggest that early changes in glucose regulation are highly dependent on the specific dietary regimen used. Specifically, TRF predominantly influences endocrine regulation (IGF-1 axis), while ADMF favours adiposity reduction. The concurrent rise in FBG may reflect a transient shift in glucose homeostasis during the early stages of fasting. Full article

With the advancement of modern competitive sports, specialized training regimens and tailored dietary patterns collectively shape a distinctive gut microbiota in athletes. This unique ecosystem exhibits high microbial diversity and is enriched with beneficial bacteria—such as short-chain fatty acid-producing strains—that contribute to enhanced athletic performance, support energy homeostasis and neural coordination, and mitigate exercise-induced injuries, thereby improving competitive outcomes. This review elaborates on the characteristics of the athlete gut microbiome across different exercise modalities, examines how microbial changes may benefit or pose risks to athlete health, and provides a unique perspective for developing microbiota-driven personalized nutrition strategies aimed at optimizing athletic performance. Full article

Background: It is widely accepted that low-grade chronic inflammation in obesity worsens the metabolic state and threatens patients’ lives in a long-term manner. In fact, diet therapy is the first-line treatment in which relevant nutrients such as the omega-3 polyunsaturated fatty acids (ω-3 PUFA) must be adequately consumed to counteract the established inflammation. In particular, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been identified as agonists of cellular receptors, including the free fatty acid receptor 4 (FFAR4), which regulates anti-inflammatory pathways associated with enhanced insulin sensitivity. However, the expression and activation of this receptor in peripheral blood mononuclear cells (PBMC) remains poorly investigated in humans. Objective: This study aimed to evaluate the effect of a diet supplemented with marine ω-3 PUFA on FFAR4 receptor activation and inflammatory markers in peripheral blood mononuclear cells in subjects with obesity. Methodology: A double-blind, randomized clinical trial (NCT05068557) was conducted over two months (eight weeks) in 55 obese individuals (aged 25–59 years). Participants were randomly assigned to one of two groups: an active placebo group (1.6 g/day of alpha-linolenic acid) or a marine ω-3 group (1080 mg of EPA and 720 mg of DHA). Both groups followed a dietary regimen with progressive calorie restriction (−200 kcal/day during weeks 0–4 and −400 kcal/day during weeks 4–8) in addition to supplementation. Results: Following the intervention, both groups showed significant improvements in body composition and biochemical parameters. Supplementation with EPA and DHA enhanced FFAR4 activation at the end of the intervention. Moreover, there was a reduction in the expression of JNK and IKKβ genes, as well as in serum levels of TNF-α, IL-6, and IL-18. In contrast, IL-10 levels increased significantly both within and between the groups. Conclusions: Marine ω-3 PUFA supplementation, in the context of a dietary intervention, promotes FFAR4 activation, thereby contributing to the modulation of the inflammatory response in human PBMC. Full article

This research aimed to examine the combined influence of Astragalus polysaccharide (APS) and Isatis indigotica extract (IIE) dietary supplements on oxidative-inflammatory status, cellular homeostasis, and intestinal integrity in large yellow croaker (Larimichthys crocea). Three replicates of experimental fish (n = 160) received one of five dietary regimens: a basal control (CON) diet, the CON diet containing 0.1% APS (AP), and the AP diet supplemented with 0.05%, 0.1%, and 0.15% IIE (AI1, AI2, and AI3) for 8 weeks. The combined supplements, particularly in the AI2 group, significantly improved intestinal morphology and enhanced the activities of key digestive enzymes. Gene expression analysis revealed that the APS-IIE combination consistently upregulated the intestinal mRNA abundance of major tight junction proteins (CLDN4, OCLN, ZO1, ZO2) compared to the CON or AP groups. Liver antioxidant capacity was strengthened (enhanced CAT capacity), as evidenced by a significant reduction in lipid peroxidation (MDA) levels. In the head kidney, the combination downregulated the expression of pro-inflammatory cytokines (IL8, TNF) and toll-like receptors (TLR1, TLR2, TLR5), and promoted the expression of anti-inflammatory cytokines (IL10, TGFB1). Furthermore, dietary supplementation modulated the crosstalk between autophagy and apoptosis, indicated by altered expression of key marker genes (e.g., increased MAP1LC3B and decreased CASP3/8/9). In conclusion, the simultaneous inclusion of APS and IIE in diets promotes intestinal health, strengthens antioxidant status, and alleviates inflammatory responses, with the 0.1% APS + 0.1% IIE (AI2) formulation demonstrating the most pronounced benefits. Full article

Proteins elicit various metabolic and physiological functions that are related to physical performance. Due to increased need in athletes, protein supplementation has been widely used to support recovery and performance. However, the extent to which acute gains in muscle protein synthesis translate into measurable performance remains debated. This narrative review synthesizes evidence from trials on supplemental proteins across resistance, endurance, and mixed-modality training, comparing sources (whey, casein, soy, pea, and blends). Moreover, this review summarizes dosing and timing strategies, with notes for master, diabetic, and female athletes. It is well-established that supplemental protein enhances fat-free mass and, to a lesser extent, strength when baseline dietary protein is suboptimal. However, the effects are smaller when habitual intake already meets athletic targets. Whey, as a rapid protein and rich in leucine, reliably elicits an acute anabolic response, while casein provides prolonged elevated aminoacidemia. When total intake and leucine thresholds are matched, plant proteins and blends can yield comparable long-term adaptations. In addition, studies showed that the distribution and strategic timing around exercise (post-exercise first, with optional pre-sleep casein or blends) support recovery during high-frequency training or energy deficit. Protein co-ingested with carbohydrate in endurance and high-intensity functional training (HIFT) can also help glycogen restoration and attenuate muscle-damage markers, though effects on sport outcomes are inconsistent. The evidence in diabetic athletes is limited; guidance extrapolates from diabetes and athlete studies, with benefits apparent when intake, quality, or distribution are limited. Furthermore, evidence indicates that anabolic resistance in master athletes requires higher per-meal doses and distribution, with post-exercise and pre-sleep feedings valuable. Consistently, female athletes partaking in aerobic and resistance training while supplementing with protein demonstrate desired body composition adaptations. Overall, although supplemental protein helps close gaps between intake and physiological demand, various factors may influence its regimen. Protein source may help the kinetics balance, amino-acid profile, and dietary preferences. Alternatively, timing may influence the protein effects on training and recovery. Full article

Reducing dietary crude protein (CP) while sustaining growth performance and minimizing nitrogen emissions is a critical challenge in swine production. Beyond growth efficiency, the influence of low-protein diets (LPDs) on meat quality traits, gut microbiota, and systemic metabolism in finishing pigs remains insufficiently understood. In this study, 180 healthy crossbred finishing pigs (Duroc × Liangguang Small Spotted; initial body weight 85.49 ± 4.90 kg) were assigned to three dietary regimens for 35 days (six replicate pens per treatment, ten pigs per pen, male/female = 1:1): Control (CON, 15.5% CP), Low-Protein 1 (LP1, 14.5% CP), and Low-Protein 2 (LP2, 13.5% CP). Growth performance and nutrient digestibility were not impaired by protein reduction. Notably, LP1 pigs exhibited thicker backfat (p < 0.05), while LP2 pigs showed decreased concentrations of specific fatty acids (C12:0–C22:1n9) and essential amino acids (aspartic acid, glutamic acid, lysine) compared with LP1 (p < 0.05), indicating that dietary protein levels affected muscle composition. Cecal microbiota analysis revealed distinct shifts, with Prevotella spp., Faecalibacterium spp., and Plesiomonas spp. enriched in CON, whereas LP1 promoted Eubacteriaceae spp., Christensenellaceae spp., and Clostridia spp. (p < 0.05). Serum metabolomics further distinguished groups: LP1 reduced bile secretion and cholesterol metabolism pathways (p < 0.05) and LP2 further suppressed cholesterol metabolism and primary bile acid biosynthesis (p < 0.05), with a trend toward reduced phenylalanine metabolism (p = 0.07). Collectively, these findings demonstrate that moderate dietary protein reduction, when balanced with essential amino acids, maintains growth, reduces nitrogen output, and beneficially alters muscle composition, gut microbiota, and host metabolic pathways, offering nutritional strategies to enhance pork quality and promote sustainable pig production. Full article

Nutritional factors play a crucial role in many gynecological disorders, particularly those influenced by estrogen. Uterine fibroids are benign tumors that affect a large proportion of women of reproductive age, especially between 30 and 40 years. These lesions may cause significant symptoms, including pelvic pain, heavy menstrual bleeding, and infertility. In younger women, the onset of fibroids is often associated with familial and genetic predisposition, whereas in adulthood, hormonal influences linked to environmental factors and states of exogenous or endogenous hyperestrogenism are more frequently observed. In both contexts, supportive management through an appropriate diet may provide clinical benefit. Although the precise pathogenesis remains incompletely understood, hormonal, genetic, and environmental components—particularly hyperestrogenism—are considered key contributors to fibroid development. Current evidence suggests that consumption of saturated fats, particularly from red meat and full-fat dairy, may raise circulating estrogen concentrations and contribute to the development of fibroids. In contrast, diets abundant in fiber, fruits, and vegetables appear to exert a protective effect, potentially lowering fibroid risk. Obesity, through increased aromatization and consequent estrogen production, also represents an established risk factor. This narrative review aims to explore the role of nutritional determinants in the onset and progression of uterine fibroids, with a specific focus on the impact of individual nutrients, foods, and dietary patterns on clinical outcomes. Particular emphasis is placed on obesity and macronutrient composition (e.g., high-fat versus high-fiber dietary regimens) as potential modulators of circulating estrogen levels and, consequently, fibroid growth dynamics. Furthermore, the potential of nutritional strategies as complementary therapeutic approaches, capable of integrating established clinical practices, is examined. Full article