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18 pages, 2660 KB  
Article
β-Hydroxybutyrate Modulates Metabolic Signaling and Partially Restores Peripheral Circadian Rhythms in High-Fat Diet-Fed Mice
by Natalie Avital-Cohen, Nava Chapnik and Oren Froy
Foods 2026, 15(8), 1305; https://doi.org/10.3390/foods15081305 (registering DOI) - 9 Apr 2026
Abstract
A high-fat (HF) diet disrupts metabolic homeostasis and impairs peripheral circadian rhythms in key metabolic tissues. β-Hydroxybutyrate (BHB), a major circulating ketone body, functions not only as an energy substrate but also as a signaling metabolite regulating nutrient-sensing and inflammatory pathways. However, its [...] Read more.
A high-fat (HF) diet disrupts metabolic homeostasis and impairs peripheral circadian rhythms in key metabolic tissues. β-Hydroxybutyrate (BHB), a major circulating ketone body, functions not only as an energy substrate but also as a signaling metabolite regulating nutrient-sensing and inflammatory pathways. However, its role in modulating metabolic–circadian interactions under conditions of nutrient excess remains unclear. In this study, we investigated whether BHB supplementation influences metabolic signaling and circadian clock oscillations in liver, skeletal muscle and adipose tissue under chow and HF conditions. Male C57BL/6 mice were fed chow or HF with or without BHB supplementation (500 mg/kg body weight in the diet) for 7 weeks. Metabolic parameters were assessed by indirect calorimetry, and tissues were collected every 4 h across the circadian cycle. HF feeding increased body weight and adiposity (p < 0.01), reduced AMPK activation, enhanced AKT/mTOR signaling, elevated NF-κB levels and dampened clock gene rhythmicity. BHB supplementation significantly decreased food intake in HF-fed mice (p < 0.01) and partially reversed several molecular alterations in a tissue-specific manner. In skeletal muscle and adipose tissue, BHB increased AMPK activation and reduced mTOR and NF-κB signaling (p < 0.05), whereas hepatic effects were more modest. Notably, BHB modulated circadian gene expression, restoring aspects of rhythmic amplitude and/or phase, particularly in adipose tissue. These findings may indicate that BHB supplementation modulates nutrient-sensing pathways and partially restores peripheral circadian rhythms under HF conditions. While some effects may be influenced by reduced energy intake, BHB may serve as a metabolic signal linking nutrient status to circadian regulation. Full article
(This article belongs to the Section Food Nutrition)
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14 pages, 567 KB  
Systematic Review
The Influence of Ultra-Processed Foods on Inflammation and Metabolic Health in Pediatric Obesity: A Systematic Review with a Narrative Synthesis
by Debora Porri, Malgorzata Wasniewska, Alessandra Li Pomi, Elisa La Rosa, Giovanni Luppino, Aurora Lanzafame, Cecilia Lugarà, Roberto Coco, Francesca Franchina, Tiziana Abbate, Carla Fazio, Valentina La Malfa, Letteria Anna Morabito, Giorgia Pepe, Mariella Valenzise, Maria Francesca Messina, Domenico Corica and Tommaso Aversa
Nutrients 2026, 18(8), 1186; https://doi.org/10.3390/nu18081186 (registering DOI) - 9 Apr 2026
Abstract
The increasing prevalence of childhood obesity has been accompanied by an increase in consumption of ultra-processed foods (UPF), characterized by high energy density and low nutritional quality. Emerging evidence suggests that dietary patterns rich in UPF may contribute to low-grade systemic inflammation and [...] Read more.
The increasing prevalence of childhood obesity has been accompanied by an increase in consumption of ultra-processed foods (UPF), characterized by high energy density and low nutritional quality. Emerging evidence suggests that dietary patterns rich in UPF may contribute to low-grade systemic inflammation and early metabolic dysfunction in children and adolescents. Objective: This systematic review aimed to evaluate the association between UPF consumption and markers of inflammation and metabolic health in pediatric populations. Methods: A systematic literature search was conducted on PubMed in accordance with PRISMA guidelines. Observational and interventional studies evaluating UPF intake or diet-related inflammatory potential in children and adolescents (≤18 years) were included. Outcomes of interest included inflammatory biomarkers (e.g., C-reactive protein, interleukins, tumor necrosis factor-α) and metabolic parameters (e.g., insulin resistance, lipid profile, glucose metabolism). Results: A limited number of studies have directly assessed UPF consumption using the NOVA classification. Overall, these studies suggest a potential association between increased UPF intake and adverse metabolic outcomes, although findings on inflammatory markers remain inconsistent. A larger body of indirect evidence, including studies assessing dietary inflammatory indices and related dietary patterns, consistently supports a link between pro-inflammatory diets and increased inflammation and metabolic dysregulation in pediatric populations. Conclusions: Although direct evidence on UPF consumption remains limited, the available findings, supported by complementary indirect evidence, suggest a plausible relationship between UPF-rich diets, inflammation, and metabolic health in children and adolescents. Further well-designed studies are needed to clarify causality and improve the standardization of dietary assessment methods. Full article
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16 pages, 3310 KB  
Article
Joint Associations of Accelerometer-Derived Intensity Gradient and Diet Quality with Frailty Among Rural Chinese Older Adults
by Ke Chen, Yating Liu, Ming Li, Meng Zhao, Kunli Wang, Ziwen Pan, Si Chen and Kefang Wang
Nutrients 2026, 18(8), 1185; https://doi.org/10.3390/nu18081185 - 9 Apr 2026
Abstract
Background/Objectives: Frailty is common among rural Chinese older adults despite relatively high daily physical activity, a phenomenon known as the “rural frailty paradox.” Conventional moderate-to-vigorous physical activity (MVPA) metrics rely on absolute cut-points and are often highly correlated with activity volume, limiting their [...] Read more.
Background/Objectives: Frailty is common among rural Chinese older adults despite relatively high daily physical activity, a phenomenon known as the “rural frailty paradox.” Conventional moderate-to-vigorous physical activity (MVPA) metrics rely on absolute cut-points and are often highly correlated with activity volume, limiting their ability to distinguish the roles of activity volume and activity intensity distribution. We therefore applied a cut-point-free accelerometer approach using average acceleration (AvAcc) and intensity gradient (IG) to distinguish activity volume from activity intensity distribution and to examine whether activity intensity distribution, together with diet quality, could help explain the rural frailty paradox beyond total activity volume alone. Methods: In this cross-sectional analysis of the Healthy Aging and Lifestyle Enhancement study, 1203 rural older adults were included. Physical activity (PA) was objectively measured using triaxial accelerometers to derive AvAcc and the IG. Diet quality was assessed using the China Prime Diet Quality Score (CPDQS), and frailty was assessed using the Fried frailty phenotype adapted for rural Chinese older adults. Multiple linear regression, joint effect models, and restricted cubic spline analyses were conducted after adjustment for age, sex, chronic disease status, total energy intake, and related covariates. Results: In mutually adjusted models, higher IG and CPDQS were independently associated with lower frailty scores, whereas AvAcc was not. In the fully adjusted model, IG (β = −0.14, p < 0.001) and CPDQS (β = −0.10, p < 0.001) were inversely associated with frailty score, while AvAcc showed no significant association (p = 0.665). In joint analyses, compared with the low-IG/low-CPDQS group, participants with high IG/high CPDQS had the lowest frailty scores (β = −0.28, p < 0.001), followed by those with low IG/high CPDQS (β = −0.20, p = 0.002). Restricted cubic spline analyses indicated a non-linear association between IG and frailty and an approximately linear inverse association for CPDQS. Conclusions: These findings suggest that, among rural older adults, frailty may be more strongly associated with activity intensity distribution than with total activity volume alone. Together with diet quality, this may help explain the rural frailty paradox. Full article
(This article belongs to the Section Geriatric Nutrition)
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14 pages, 606 KB  
Article
Higher Ultra-Processed Food (UPF) Intake Is Associated with Lower Food Literacy in Greek Adults with Overweight or Obesity: Results from a Cross-Sectional Study
by Maria Ioannidou, Marios Skordis, Ioannis Kavvadias, Georgios I. Panoutsopoulos and Evaggelia Fappa
Dietetics 2026, 5(2), 24; https://doi.org/10.3390/dietetics5020024 - 9 Apr 2026
Abstract
Background: Given the limited evidence in the field, the present study aimed to explore the association of UPF intake with food literacy levels in an adult Mediterranean-based population. Methods: Self-reported demographic and anthropometric data were collected from 317 apparently healthy adults (52.5% males) [...] Read more.
Background: Given the limited evidence in the field, the present study aimed to explore the association of UPF intake with food literacy levels in an adult Mediterranean-based population. Methods: Self-reported demographic and anthropometric data were collected from 317 apparently healthy adults (52.5% males) Food literacy and dietary intake of this population were also assessed. Foods were classified as ultra-processed according to the NOVA system, and their contribution to total daily energy intake (%) was calculated. Then, participants were grouped into the (1) higher UPF intake (HUPFI), and (2) lower UPF intake (LUPFI) groups, based on the median value of this population as a cut-off. Results: Between-group analysis revealed that LUPFI scored statistically significantly higher than the HUPFI group in total food literacy (93.5 [84.0–104.0] vs. 86.0 [78.0–99.0], p < 0.001) and in three out of five food literacy sub-dimensions. Sub-analysis revealed no differences between LUPFI and HUPFI groups of individuals with normal weight. In participants with overweight or obesity, the LUPFI group scored lower than the HUPFI in the total food literacy score (95.0 [87.0–104.0] vs. 81.0 [70.0–94.0], p < 0.001) and in each sub-dimension. Conclusions: Higher UPF intake was associated, in adults with overweight or obesity, with lower levels of food literacy. Full article
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18 pages, 2187 KB  
Review
A Conceptual Framework for Managing Oral Intake in Head and Neck Cancer Patients Undergoing Chemoradiotherapy
by Marco Cintoni, Elena Leonardi, Pauline Celine Raoul, Silvia Longo, Mariangela Massaccesi, Marta Palombaro, Gabriele Egidi, Francesco Pastore, Emanuele Rinninella, Esmeralda Capristo, Antonio Gasbarrini, Maria Antonietta Gambacorta and Maria Cristina Mele
Nutrients 2026, 18(8), 1180; https://doi.org/10.3390/nu18081180 - 9 Apr 2026
Abstract
Patients with head and neck cancer (HNC) face a high risk of malnutrition and sarcopenia, often exacerbated by the toxicities of chemoradiotherapy, such as dysphagia, xerostomia, and mucositis. These Nutritional Impact Symptoms significantly compromise oral intake and negatively affect quality of life. This [...] Read more.
Patients with head and neck cancer (HNC) face a high risk of malnutrition and sarcopenia, often exacerbated by the toxicities of chemoradiotherapy, such as dysphagia, xerostomia, and mucositis. These Nutritional Impact Symptoms significantly compromise oral intake and negatively affect quality of life. This paper presents a conceptual framework designed to support clinicians in optimizing oral intake through personalized nutritional management. Central to this approach is the integration of systematic screening using MUST, the Malnutrition Universal Screening Tool (MUST), and the Nutritional Risk Screening 2002 (NRS-2002). Furthermore, functional assessment of swallowing via instrumental studies (VFSS/FEES) is essential for tailoring dietary textures according to the International Dysphagia Diet Standardization Initiative framework. Key nutritional strategies include high-energy and high-protein oral fortification, the use of oral nutritional supplements, and specific dietary adjustments addressing pain management and sensory alterations. A multidisciplinary approach involving nutritionists, speech-language pathologists, and oncologists is paramount to transition from reactive symptom management to proactive “adaptive nutrition,” ultimately improving clinical outcomes and patient survival. Full article
(This article belongs to the Section Clinical Nutrition)
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13 pages, 282 KB  
Article
Serum 25-Hydroxyvitamin D Concentration and Aerobic Performance in Estonian Female Adolescent Athletes
by Jaak Jürimäe, Liina Remmel, Priit Purge and Vallo Tillmann
Appl. Sci. 2026, 16(8), 3643; https://doi.org/10.3390/app16083643 - 8 Apr 2026
Abstract
Vitamin D insufficiency is highly prevalent in athletic populations residing at northern latitudes, particularly among young athletes training predominantly indoors. The impact of vitamin D on musculoskeletal health is well-established, while its influence on physical performance is not entirely clear. The aim of [...] Read more.
Vitamin D insufficiency is highly prevalent in athletic populations residing at northern latitudes, particularly among young athletes training predominantly indoors. The impact of vitamin D on musculoskeletal health is well-established, while its influence on physical performance is not entirely clear. The aim of this study was to determine the prevalence of vitamin D insufficiency in Estonian female adolescent athletes and to examine associations of serum 25-hydroxyvitamin D [25(OH)D] with body composition, energy intake, physical performance and ferritin. Seventy-three female athletes aged 14–18 years participated. Body composition was assessed by dual-energy X-ray absorptiometry; physical performance by peak oxygen consumption (VO2peak/kg) and countermovement jumps; dietary intake was estimated using repeated 24 h recalls; and fasting blood samples were analyzed for 25(OH)D and ferritin. The mean serum 25(OH)D concentration was 67.6 ± 21.4 nmol.L−1 and ranged from 27.4 to 118.0 nmol.L−1. Vitamin D insufficiency (25(OH)D < 75 nmol.L−1) was present in 67% of participants, leaving only one-third with sufficient levels. Serum 25(OH)D concentration was positively associated with VO2peak/kg (r = 0.26; p = 0.043) independent of confounding variables. In conclusion, these findings suggest that vitamin D insufficiency is highly prevalent among Estonian female adolescent athletes, and 25(OH)D concentration is associated with aerobic performance. Full article
(This article belongs to the Special Issue Children's Exercise Medicine: Bridging Science and Healthy Futures)
12 pages, 236 KB  
Article
Linking Inflammation to Reduced Food Intake in Advanced Cancer: A Prospective Observational Study
by Asta Bye, Trude Rakel Balstad, Ida Ervik Raaness, Tora Skeidsvoll Solheim, Ragnhild Habberstad, Pål Klepstad, Erik Torbjørn Løhre, Olav Faisal Dajani, Stein Kaasa, Nina Aass and Ola Magne Vagnildhaug
Curr. Oncol. 2026, 33(4), 209; https://doi.org/10.3390/curroncol33040209 - 8 Apr 2026
Abstract
Background: Undernutrition and cachexia are common in advanced cancer and often linked to systemic inflammation. While inflammation is associated with poorer prognosis, accelerated weight loss, and reduced treatment tolerance, its direct impact on food intake remains insufficiently investigated. Aim: To examine [...] Read more.
Background: Undernutrition and cachexia are common in advanced cancer and often linked to systemic inflammation. While inflammation is associated with poorer prognosis, accelerated weight loss, and reduced treatment tolerance, its direct impact on food intake remains insufficiently investigated. Aim: To examine the association between systemic inflammation and energy and protein intake over time in patients with advanced cancer. Methods: A total of 170 patients from the Palliative Radiotherapy and Inflammation Study were included. Nutritional status was assessed using PG-SGA SF. Dietary intake was recorded using repeated 24 h recalls. Systemic inflammation was defined as CRP > 10 mg/L. Mixed linear models were applied to evaluate the association between inflammation energy and protein intake over time. Results: Systemic inflammation (CRP >10 mg/L) was present in 87 (51%) patients and associated with significantly lower energy (−3.6 kcal/kg, p = 0.04) and lower protein intake (−0.25 g/kg, p = 0.003). Patients with inflammation were more often undernourished and had shorter survival. Conclusions: Systemic inflammation is likely associated with clinically relevant reductions in energy and protein intake in advanced cancer. CRP may help identify patients for whom standard nutritional support is insufficient. Full article
(This article belongs to the Special Issue Palliative Care in Oncology: Current Advances)
4 pages, 201 KB  
Editorial
New Updates in Adipocytes and Adipose Tissue: 2nd Edition
by Endre Kristóf and Éva Csősz
Life 2026, 16(4), 619; https://doi.org/10.3390/life16040619 - 7 Apr 2026
Abstract
Long-term imbalance between energy intake and expenditure, coupled with genetic susceptibility, results in excess adiposity associated with deleterious outcomes across a broad range of cell and tissue types [...] Full article
(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue: 2nd Edition)
16 pages, 294 KB  
Article
The Relationship Between Eating Habits and Anthropometric Values in High School Adolescents
by Lucija Firi, Dubravka Mihaljević, Ivan Prošić, Kristina Kralik, Ana Stupin, Ivana Jukić and Ines Drenjančević
Life 2026, 16(4), 618; https://doi.org/10.3390/life16040618 - 7 Apr 2026
Abstract
Objectives: The present study aimed to examine the relationship between dietary habits and anthropometric characteristics of high school adolescents. Participants and Methods: This cross-sectional study involved randomly selecting 104 students (34 boys and 70 girls) who were 17–19 years old. To evaluate dietary [...] Read more.
Objectives: The present study aimed to examine the relationship between dietary habits and anthropometric characteristics of high school adolescents. Participants and Methods: This cross-sectional study involved randomly selecting 104 students (34 boys and 70 girls) who were 17–19 years old. To evaluate dietary habits, a validated and standardized EPIC-Norfolk frequency food questionnaire was used, and anthropometric characteristics of the participants were assessed. Results: The most often consumed foods during the week were meats and fruits, while the least frequently consumed were fish and vegetables. For all participants, intake below the recommended levels was for alpha-carotene, total carbohydrate sugars, vitamin D, milk, dairy products, nuts, and seeds. Intake of proteins and iron was below the recommended levels in girls. Boys had a lower intake of proteins and fruits compared to girls. No differences were observed in the consumption of macronutrients. The median of all anthropometric values was within the reference values. Boys were slightly older and had significantly higher values of body weight and height, BMI, waist circumference, and waist-to-hip-ratio (WHR) compared to girls. In addition, systolic blood pressure (SBP) was significantly higher in males than in females. Participants with increased arterial blood pressure (ABP) showed significantly higher energy intake from fat, sodium intake, and total fat intake compared to those with normal ABP. Participants with increased WHR had significantly higher energy intake, intake of sodium, and total carbohydrates compared to those with normal WHR. Conclusions: This study shows that adolescents’ eating habits (particularly intake of fat and sodium) were associated with anthropometric values, ABP, and WHR, which present risks for cardiometabolic diseases in adulthood. Full article
(This article belongs to the Section Physiology and Pathology)
31 pages, 7511 KB  
Article
Synergistic Analysis of Methanol–Diesel Combustion for a Marine Diesel Engine: An Integrated CFD and Experimental Method
by Zixiao Ye, Ke Chen, Jialiang Huang, Zibin Yin, Peicun Zhang, Yuchen Liu, Jinyu Fan and Zhiqing Zhang
Energies 2026, 19(7), 1794; https://doi.org/10.3390/en19071794 - 7 Apr 2026
Abstract
With the growth of global maritime transportation volume and fuel shortages caused by excessive oil consumption, energy conservation and emission reduction technologies for marine diesel engines have become a core research focus. A three-dimensional (3D) CFD model of a methanol–diesel dual-fuel marine diesel [...] Read more.
With the growth of global maritime transportation volume and fuel shortages caused by excessive oil consumption, energy conservation and emission reduction technologies for marine diesel engines have become a core research focus. A three-dimensional (3D) CFD model of a methanol–diesel dual-fuel marine diesel engine was developed in AVL-FIRE and coupled with a CHEMKIN reaction mechanism. The model was validated against experimental data, with errors in cylinder pressure, heat release rate, and major emissions below 5%. Based on the validated model, the effects of the methanol blending ratio (0–30%), injection advance angle, intake temperature, intake pressure, and EGR rate on combustion and emissions were investigated. The results show that increasing the methanol blending ratio reduced cylinder pressure, in-cylinder temperature, and NO and soot emissions, while increasing the peak heat release rate. Advancing injection timing improved combustion and reduced CO and soot emissions but increased NO formation. Higher intake temperature worsened combustion performance and increased NO, CO, and soot emissions. Orthogonal analysis and regression-based optimization identified an optimal condition with a methanol blending ratio of 27%, an EGR of 12.5%, an injection advance angle of 21.2 °CA, an intake temperature of 319.05 K, and an intake pressure of 0.223 MPa. Under this condition, the NOx mass fraction was 1.65 × 10−5. Full article
(This article belongs to the Topic Advanced Bioenergy and Biofuel Technologies)
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16 pages, 1159 KB  
Article
Development and Validation of an Algorithm for Constructing an Amino Acid Database for Application to the Korean Genome and Epidemiology Study Cohort
by Su-Jin Lee and Ji-Yun Hwang
Nutrients 2026, 18(7), 1147; https://doi.org/10.3390/nu18071147 - 2 Apr 2026
Viewed by 275
Abstract
Background/Objectives: The Korean Genome and Epidemiology Study (KoGES) is a large population-based cohort designed to investigate chronic disease risk using long-term dietary and health data. However, comprehensive amino acid information for estimating long-term intake from food frequency questionnaire (FFQ) data remains limited. This [...] Read more.
Background/Objectives: The Korean Genome and Epidemiology Study (KoGES) is a large population-based cohort designed to investigate chronic disease risk using long-term dietary and health data. However, comprehensive amino acid information for estimating long-term intake from food frequency questionnaire (FFQ) data remains limited. This study aimed to develop and validate a standardized, rule-based algorithm for food matching and substitution and to construct an amino acid database applicable to the KoGES FFQ. Methods: The algorithm sequentially evaluated food name concordance, preparation forms, substitutability of similar foods, and differences in energy, macronutrients, and moisture (±20%). Amino acid composition data were derived from domestic and international food composition tables and published literature, with protein–nitrogen conversion factors applied by food group. Results: Amino acid information was established for 475 FFQ food items covering 19 amino acids. Of the database values, 31.0% were analytical, 64.2% were calculated, and 4.8% were substituted. Overall database coverage across all amino acid–food item combinations was 98.8%. The constructed database was applied to dietary data from the second follow-up (Phase 3) of the KoGES Ansan and Ansung community-based cohorts, showing that total amino acid intake accounted for 86.7% of total protein intake, reflecting the inclusion of non-protein nitrogen in conventional protein estimates. Based on the Estimated Average Requirement (EAR) criteria, the proportions of participants with intakes below the EAR for protein and essential amino acids varied across age and sex groups. Overall and in both men and women, lysine showed the highest proportion of participants below the EAR, whereas tryptophan showed the lowest proportion. Conclusions: This standardized algorithm provides a reproducible framework for constructing amino acid databases and can be applied to large-scale cohort and dietary survey data. Full article
(This article belongs to the Section Nutritional Epidemiology)
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20 pages, 628 KB  
Article
Nutritional Status and Dietary Assessment in Kidney Transplant Recipients
by Martyna Magalska and Sylwia Małgorzewicz
Nutrients 2026, 18(7), 1145; https://doi.org/10.3390/nu18071145 - 2 Apr 2026
Viewed by 287
Abstract
Background: Proper nutrition plays a crucial role in post-kidney transplantation care, influencing graft function, body composition, and the risk of metabolic complications. Protein intake is of particular importance due to its role in preserving muscle mass and preventing protein energy wasting. Objective: This [...] Read more.
Background: Proper nutrition plays a crucial role in post-kidney transplantation care, influencing graft function, body composition, and the risk of metabolic complications. Protein intake is of particular importance due to its role in preserving muscle mass and preventing protein energy wasting. Objective: This study aimed to assess dietary intake, with emphasis on protein consumption, and to analyze its associations with nutritional status, anthropometric indices, and metabolic complications in kidney transplant recipients. Materials and Methods: A cross-sectional study was conducted in 71 adult kidney transplant recipients. Dietary intake was assessed using a 24 h dietary recall and the FFQ-6 questionnaire. Anthropometric measurements were performed, and multiple indices of body composition and central obesity were calculated. Associations between dietary intake, anthropometric parameters, age, and kidney graft function were analyzed. Results: Mean BMI was within the upper normal range; however, a high prevalence of central adiposity was observed. Age was positively correlated with indices of visceral obesity (ABSI, AVI, WHtR, and CI). Protein intake was positively associated with calf circumference, indicating a relationship with muscle mass preservation. Dietary analysis revealed excessive sodium intake and insufficient intake of potassium, calcium, vitamin D, and unsaturated fatty acids. Post-transplant diabetes mellitus was present in 25.35% of participants. Conclusions: Kidney transplant recipients frequently present with unfavorable body composition and dietary imbalances that are not adequately reflected by BMI alone. Comprehensive nutritional assessment and individualized dietary counseling are important strategies that may help reduce the risk of metabolic complications and support long-term transplant outcomes. Full article
(This article belongs to the Special Issue Kidney Nutrition and Metabolism)
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11 pages, 705 KB  
Perspective
The Emerging Role of N-Lactoyl-Phenylalanine (Lac-Phe) in Metabolic Regulation and Disease: From Exercise-Induced Metabolite to Therapeutic Candidate
by Julia Chu-Ning Hsu, Chia-Hui Chen, Ming-Wei Chen, Wen-Hua Chen and Tzong-Shyuan Lee
Antioxidants 2026, 15(4), 441; https://doi.org/10.3390/antiox15040441 - 1 Apr 2026
Viewed by 332
Abstract
N-Lactoyl-phenylalanine (Lac-Phe), identified in 2022 as an exercise-inducible signaling metabolite, is formed by carnosine dipeptidase 2 via conjugation of lactate and phenylalanine. Its circulating levels rise sharply after intense exercise in mice, humans, and racehorses, reflecting increased glycolytic flux. Beyond exercise, Lac-Phe also [...] Read more.
N-Lactoyl-phenylalanine (Lac-Phe), identified in 2022 as an exercise-inducible signaling metabolite, is formed by carnosine dipeptidase 2 via conjugation of lactate and phenylalanine. Its circulating levels rise sharply after intense exercise in mice, humans, and racehorses, reflecting increased glycolytic flux. Beyond exercise, Lac-Phe also rises with feeding and metformin, positioning it as a potential integrator of energy intake, expenditure, and metabolic homeostasis. Centrally, Lac-Phe may contribute to appetite suppression by inhibiting hypothalamic orexigenic agouti-related protein neurons, primarily observed in obese rodent models, while sparing anorexigenic pro-opiomelanocortin neurons, thereby reducing food intake, promoting weight loss, and improving glucose tolerance in obese models without altering energy expenditure. Peripherally, it drives anti-inflammatory M2 macrophage polarization, ameliorating colitis and aiding recovery after spinal cord injury via NF-κB suppression and reactive oxygen species reduction. As a biomarker, Lac-Phe may offer advantages over lactate in reflecting mitochondrial dysfunction in conditions such as MELAS, sepsis, and NADH-reductive stress; however, these observations derive mainly from small-scale or exploratory studies and require prospective validation. Recent studies from 2024 to 2025 further reveal its partial and context-dependent role in mediating metformin’s effects, intensity- and sex-dependent responses, renal clearance via SLC17A1/3 transporters, and links to exercise-induced redox adaptations. The first human phase I trial (NCT06743009), launched in 2025, is assessing the metabolic effects of Lac-Phe in obesity. This Perspective summarizes Lac-Phe biosynthesis, physiological mechanisms, including its emerging but largely correlative connections to redox homeostasis, and therapeutic promise, underscoring its potential relevance for exercise-mimicking strategies in metabolic, inflammatory, and redox-related disorders. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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29 pages, 2064 KB  
Review
Circadian Timekeeping Through Nutritional and Metabolic Sensory Networks
by Erin N. Doherty and Lauren N. Woodie
Nutrients 2026, 18(7), 1133; https://doi.org/10.3390/nu18071133 - 31 Mar 2026
Viewed by 414
Abstract
Circadian rhythms are predictable biological patterns that recur about every 24 h and, in mammals such as humans, are entrained to daylight by the hypothalamic suprachiasmatic nucleus (SCN). Although light is a potent zeitgeber for the SCN, cells outside of the SCN can [...] Read more.
Circadian rhythms are predictable biological patterns that recur about every 24 h and, in mammals such as humans, are entrained to daylight by the hypothalamic suprachiasmatic nucleus (SCN). Although light is a potent zeitgeber for the SCN, cells outside of the SCN can synchronize to daily nutrient and metabolic cues. In these tissues, nutrient metabolic processes are regulated by the molecular clock in anticipation of food availability or scarcity. Furthermore, nutrients and metabolic processes themselves may act upon members of the molecular clock to regulate their expression and activity. These interactions maintain synchrony between the SCN and food-entrainable clocks when activity and nutrient intake align. However, the light-entrainable SCN and food-entrainable clocks can become desynchronized, particularly in modern society where humans are commonly exposed to shift work and jet lag. Therefore, the mechanisms for sensing nutrients at specific times of day are critical components of circadian timekeeping and organismal homeostasis. In the following narrative review, we aim to synthesize current evidence on time-of-day-dependent nutrient sensing in mammalian systems, examine how nutrient-derived signals and metabolic processes interact with molecular clock mechanisms across cellular and tissue levels, and evaluate the integration of central and peripheral clocks in regulating gene expression, energy utilization, and organismal homeostasis, including the impacts of feeding cycles and circadian disruption. While previous reviews have discussed circadian nutrient metabolism, this review provides conceptual support for the role of nutrients as time-of-day signaling mechanisms. Full article
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14 pages, 371 KB  
Article
Association Between Mineral Intake and Cognitive Performance in Spanish Adults with Overweight and Obesity: A Cross-Sectional Study
by Mario Tomé-Fernández, Laura Martín-Manchado, Miriam Sánchez-Sansegundo, Ana Zaragoza-Martí, Jorge Azorín-López and José Antonio Hurtado-Sánchez
Nutrients 2026, 18(7), 1129; https://doi.org/10.3390/nu18071129 - 31 Mar 2026
Viewed by 302
Abstract
Background/Objectives: While adequate mineral intake is essential for brain health and cognitive function across the lifespan, the potential impact of excessive consumption remains underexplored. This study aimed to examine the association between dietary intake of selected minerals, with particular focus on iron [...] Read more.
Background/Objectives: While adequate mineral intake is essential for brain health and cognitive function across the lifespan, the potential impact of excessive consumption remains underexplored. This study aimed to examine the association between dietary intake of selected minerals, with particular focus on iron and zinc, and cognitive performance in Spanish adults with obesity, particularly in executive-related domains such as reasoning, cognitive flexibility, and working memory. Methods: A cross-sectional study was conducted in 230 Spanish adults (18–65 years) from the Tech4Diet-Person project. Sociodemographic, dietary, and cognitive data were collected between 2021 and 2024. Cognitive function was assessed using the validated computerized CogniFit battery, and mineral intake was estimated through a food frequency questionnaire (93 items). Individuals with neurological, metabolic, or psychiatric disorders, as well as pregnant or lactating women, were excluded. Results: Participants had a mean age of 45.91 (±9.92) years. Nominal differences in mineral intake were observed across specific executive cognitive domains. Higher dietary iron intake was associated with lower performance in reasoning and cognitive flexibility, while higher zinc intake was associated with lower working memory performance. In adjusted logistic regression models, higher iron intake was independently associated with increased odds of low reasoning performance (OR = 1.25; p = 0.006), and higher zinc intake was associated with increased odds of low working memory performance (OR = 1.36; p = 0.024), after controlling for age, educational level, BMI, and total energy intake. Conclusions: Higher self-reported intake of iron and zinc showed nominal associations with lower performance in specific executive domains. These findings should be considered exploratory and require confirmation in longitudinal and biomarker-based studies. Full article
(This article belongs to the Section Micronutrients and Human Health)
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