Nutrition, Obesity and Metabolic Diseases

Background: Obesity is a chronic metabolic disease characterized by lipid overload, low-grade inflammation, oxidative stress, and progressive organ dysfunction. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been increasingly implicated in obesity-related complications. However, an acute cell death-centered model does not fully explain the chronic senescence-like decline observed in metabolic tissues. The recently proposed concept of ferro-aging provides a potential framework for linking iron-dependent lipid peroxidation to cellular senescence and metabolic aging. Methods: In this review, we combined bibliometric mapping with mechanistic synthesis to characterize the evolving research landscape of ferroptosis in obesity and integrate the emerging concept of ferro-aging into this field. Bibliometric analysis was performed to screen qualified literature, and keyword co-occurrence and co-citation analyses were conducted to extract mainstream research hotspots. We further systematically summarized the pathological microenvironment constructed by obesity and the core molecular mediator connecting ferroptosis and ferro-aging, and proposed a pathological continuum hypothesis for obesity-mediated lipid peroxidation injury. Results: A total of 564 eligible publications were identified, including 455 original articles and 109 reviews, with a marked increase in publication output after 2020. Keyword and co-citation analyses highlighted oxidative stress, lipid peroxidation, iron metabolism, GPX4/Nrf2-mediated antioxidant defense, mitochondrial dysfunction, gut microbiota, NAFLD, and DCM as major research themes. Mechanistically, obesity creates a pro-ferroperoxidative microenvironment through iron dysregulation, polyunsaturated fatty acid enrichment, chronic inflammation, mitochondrial stress, and impaired antioxidant capacity. Within this context, ACSL4 is proposed as a candidate molecular hub that may link acute ferroptotic injury with chronic iron-lipid peroxidation-driven cellular senescence. We proposed a hypothesis-generating framework. In this framework, acute lipid peroxidation may promote ferroptotic cell death. Persistent sublethal iron-lipid peroxidation stress may contribute to ferro-aging-like senescence. Conclusions: To our knowledge, this is the first review to place ferro-aging within the obesity-ferroptosis framework. Targeting the ACSL4-lipid peroxidation axis and restoring antioxidant defense, particularly through Nrf2-GPX4-related pathways, may provide new translational opportunities for stratifying and managing obesity-related complications. However, clinical validation of ferro-aging biomarkers and intervention strategies remains urgently needed. Full article

Diet-induced obesity contributes to chronic inflammation, mitochondrial dysfunction, and progressive kidney injury, while increased dietary acid load may further impair renal homeostasis. In our previous studies, we showed that ammonium hydroxide enhancement (AHE) of dietary protein, prior to incorporation into the complete diet, increases dietary alkalinity and has improved longevity, decreased secretion of adipocytokines, and beneficially affected the microbiome in high-fat diet fed C3H/HeJ mice. However, its effects on renal molecular and structural responses remain unknown. In this study, kidney tissues from male C3H/HeJ mice fed control casein (CC), ammonium hydroxide-enhanced casein (CCN), high-fat casein (HFC), ammonium hydroxide-enhanced high-fat casein (HFCN), high-fat beef (HFB), or ammonium hydroxide-enhanced high-fat beef (HFBN) diets were analyzed using quantitative PCR, Western blotting, and histological morphometry. Results showed that AHE reduced renal inflammatory signaling, evidenced by decreased TLR4, TNFα, Il1-β, IL6, and NFκB expression. Apoptosis-associated signaling was attenuated through reduced Caspase-3 and p53 expressions and increased BCL2 levels. AHE also modulated mitochondrial-associated markers. Increased markers of mitochondrial biogenesis and fusion, and decreased fission-associated markers were observed, along with increased PINK1 expression, while Parkin remained unchanged. In addition, expression levels of the ammonia transporters, RHBG and RHCG, were elevated, indicating altered renal ammonia transporter expression. Histological and morphometric analyses demonstrated AHE-associated changes in tubular areas, while glomerular and Bowman’s capsule areas remained largely unchanged. Collectively, these findings suggest that long-term dietary AHE is associated with alterations in renal inflammatory and apoptotic signaling, mitochondrial-associated pathways, ammonia transporter expression, and renal histomorphometry in male C3H/HeJ mice. Full article

Introduction: Sarcopenia and obesity are increasingly recognized as overlapping conditions that contribute to adverse health outcomes, particularly in rapidly urbanizing populations. The coexistence of both conditions, termed sarcopenic obesity, represents a complex phenotype with potentially greater metabolic burden, yet its differentiation from non-obese sarcopenia remains insufficiently explored. Aim: This study aimed to compare metabolic and cardiometabolic profiles between sarcopenic obesity and non-obese sarcopenia in an urban population. Methods: A cross-sectional study was conducted using secondary data from the PRIMBON 2025 database in Jakarta, Indonesia. Participants were adults aged ≥18 years diagnosed with sarcopenia based on the 2025 Asian Working Group for Sarcopenia (AWGS) criteria. Sarcopenic obesity was defined according to the 2025 AOASO–IAGG consensus using BMI ≥ 25 kg/m² and visceral fat level > 10. A total of approximately 604 participants were included from five administrative regions of Jakarta. Data were analyzed using Mann–Whitney U test and Chi-square test, with results presented as median (min–max), mean rank, and odds risk (OR). A dot-and-whisker plot was used to visualize effect sizes. Results: Sarcopenic obesity was associated with older age and a higher proportion of males (p < 0.01). Significant differences were observed in systolic and diastolic blood pressure, fasting blood glucose, triglycerides, and HDL (all p < 0.01), indicating a more adverse cardiometabolic profile. No significant differences were found for hemoglobin, total cholesterol, LDL, uric acid, and handgrip strength. Conclusions: Sarcopenic obesity represents a more severe metabolic phenotype compared to non-obese sarcopenia. Full article

Background/Objective: Maternal diet is an important determinant of gut microbiota composition in dams and offspring. This study investigated whether HDCA supplementation during maternal high-fat diet (HFD) exposure was associated with gut microbiota composition in dams and offspring and with selected obesity-related phenotypes. Methods: Nineteen C57BL/6J female mice were assigned to a control diet group (CON), a high-fat diet group (HFD), and a high-fat diet supplemented with 0.5% hyodeoxycholic acid group (HFD+HDCA). Fecal samples were collected from the dams before mating, following 8 weeks of dietary intervention, and from the offspring at weaning. All samples were analyzed using 5R 16S rRNA gene sequencing. Body weight was monitored in both dams and offspring, and liver histology was assessed by hematoxylin and eosin staining. Results: HFD exposure was associated with obesity-related phenotypes in dams and offspring, including increased maternal body weight and greater hepatic lipid accumulation and visceral adiposity in offspring. LEfSe and ANCOM-BC2 analyses identified concordant microbial changes between dams and offspring under corresponding dietary conditions. Lachnospiraceae_Unknown_genus3261 and Coprococcus increased with HFD exposure in both dams and offspring, whereas Bifidobacterium, Coprococcus, and Allobaculum decreased following HDCA supplementation. These findings indicate maternal–offspring concordance in microbiota responses to HFD and HDCA, without establishing direct vertical transmission. PICRUSt2 analysis suggested group association differences in predicted functional potential for pathways annotated to propionate, pyruvate, and β-alanine metabolism. Conclusions: HDCA supplementation during maternal HFD exposure was associated with differences in offspring gut microbiota at weaning and with attenuation of selected obesity-related phenotypes. These findings suggest a potential role of the gut microbiota–bile acid axis in mediating intergenerational dietary effects. However, the study does not establish direct microbial transmission, altered metabolic activity, or causality; these findings require confirmation in litter-aware and mechanistic studies. Full article

Background and Objectives: The pandemic caused by the SARS-CoV-2 infection has been named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). Cancer patients may have been more adversely affected during the COVID-19 Pandemic due to their receipt of immunosuppressive treatments, higher burden of comorbidities, and greater nutritional vulnerability compared to the general population. The aim of our study is to identify potential measures by detecting changes in the nutritional statuses of patients with an oncological diagnosis who presented to our hospital during the COVID-19 pandemic, using the globally accepted NRS-2002 questionnaire. Materials and Method: Our study included 324 patients diagnosed with malignancy who applied to the outpatient clinic of Gaziantep University, Şahinbey Training and Research Hospital, Gaziantep/Türkiye, between December 2021 and January 2022 or were hospitalized in the service. Patients included in the study were evaluated in terms of clinical–demographic information and COVID-19-related characteristics using a sociodemographic data form we developed, and then the NRS-2002 questionnaire was administered. Results: Our study included 324 patients. Overall, 49.07% (159 patients) of the patients were male, and 50.93% (165 patients) were female. A total of 20.37% of our patients (66 patients) had COVID-19 disease. While those living with their families constituted 96.91% of the patients, at least one of the family members of 36.42% of the patients had COVID-19 disease. While 76.23% (247 patients) of the patients were vaccinated, 23.77% (77 patients) were not vaccinated. When NRS analyses were examined according to the type of malignancy, a statistically significant difference was found between NRS analyses according to the type of diagnosis. When NRS analyses were examined according to the stages of the diseases, it was determined that stage 4 patients were in the risk group in terms of nutrition. When NRS analyses according to age were examined, it was determined that patients over the age of 65 were in the risk group in terms of nutrition. When NRS analyses by gender were examined, it was found that male patients were in the risk group in terms of nutrition. When the NRS analyses were examined according to whether or not radiotherapy was administered, it was determined that the patients who received radiotherapy were in the risk group in terms of nutrition. Contrary to the literature, no statistically significant difference was found according to whether or not chemotherapy was administered. Conclusions: According to NRS analysis, no statistically significant differences were found in terms of nutritional status according to COVID-19 transmission and vaccination status. When NRS analyses were examined according to the delay of treatment during the pandemic period, it was found that patients who postponed treatment were in the risk group in terms of nutrition, while patients who did not postpone treatment were mostly in the follow-up group. In multivariable analyses, however, no independent relationship was identified between this parameter and NRS-2002 risk. Full article

Maternal obesity has been associated with offspring fetal programming, increasing the risk of developing chronic diseases in adulthood, including type 2 diabetes, hypertension, and behavioral disorders such as anxiety and depression. Milk whey (MW) peptides, administered as a supplement, reduce food intake and body weight in overweight rodents. The aim of this work was to study the possible metabolic and behavioral restorative effects of a bovine MW supplement against the negative fetal programming of juvenile offspring. Dam Wistar rats were fed during gestation and lactation with a standard (SD) or a hypercaloric diet (HD); after weaning, the male offspring were fed SD or SD and MW. HD dams showed increases in blood cholesterol, body weight, and calorie intake, while administering MW in offspring from HD mothers reduced these alterations. Serum corticosterone, LDL cholesterol, fasting blood glucose, and glucose intolerance were significantly higher in offspring from HD dams; however, MW did not affect these changes. Offspring from HD dams showed signs of anxiety that were not reversed by MW, as well as a reduction in hippocampal BDNF that was partially restored with MW. Maternal HD consumption during pregnancy and lactation elicited negative developmental programming of adult offspring metabolism, which was partially restored by bovine MW supplementation. Full article

Background: Classical phenylketonuria (PKU) requires the lifelong dietary restriction of phenylalanine-containing foods. In this study, we aimed to evaluate the effects of a phenylalanine-restricted diet on carnitine, amino acid, vitamin, and mineral status in children with classical PKU. Methods: This case–control study included 30 children with classical PKU and 30 age- and sex-matched healthy controls. Dietary adherence was categorized as good, moderate, or poor according to blood phenylalanine concentrations during the preceding year. Dried blood spot amino acid and acylcarnitine profiles combined with serum micronutrient and hematological parameters were analyzed. Results: No significant differences were observed between the PKU and control groups regarding tyrosine, free carnitine (C0), acetyl carnitine (C2), valine, or methionine concentrations (p > 0.05). Arginine levels were significantly lower in the PKU group than in controls (40.14 ± 29.89 vs. 48.25 ± 16.08 µmol/L, p = 0.008). Vitamin B12, folate, 25-hydroxyvitamin D, and mean corpuscular volume were significantly higher in patients with PKU (all p < 0.05). Dietary adherence exhibited a strong negative correlation with phenylalanine concentrations (r = −0.86, p < 0.001), a moderate negative correlation with the phenylalanine-to-tyrosine ratio (r = −0.56, p = 0.001), and a moderate negative correlation with body mass index (r = −0.55, p = 0.002). Conclusions: Children with classical PKU receiving long-term dietary treatment maintained adequate carnitine and micronutrient status. Reduced arginine concentrations observed in treated children with classical PKU warrant further investigation, although their clinical significance remains uncertain. Full article

Smoking and central obesity have both been linked to periodontitis, but their combined relationship with periodontal disease may be influenced by demographic and behavioral factors. This cross-sectional study analyzed records of 420 adult dental patients attending the College of Dentistry at the University of Baghdad. Data included demographic characteristics, smoking status, periodontal clinical findings, body mass index (BMI), and waist-to-height ratio (WHtR). Periodontitis was defined according to the 2018 classification framework, and logistic regression models were used to examine the associations of smoking and obesity-related indicators with periodontitis. The overall prevalence of periodontitis was 36.4%. Participants with periodontitis were significantly older than those without periodontitis (46.0 vs. 28.9 years; p < 0.0001). In the fully adjusted model, age remained the strongest factor associated with periodontitis (OR = 1.15 per year; 95% CI: 1.11–1.18; p < 0.001). The apparent association between smoking and periodontitis was substantially influenced by age, as current smoking was more common among younger participants in this sample. The association between smoking status and periodontitis appeared to differ according to WHtR category (interaction term p = 0.016); however, this finding should be interpreted cautiously because of the cross-sectional design and age imbalance across exposure groups. Overall, the findings suggest that age was the dominant factor associated with periodontitis in this dental patient sample, while the relationship between smoking, central obesity, and periodontitis requires further investigation in longitudinal studies with detailed smoking and metabolic data. Full article