Background/Objectives: We investigated the effects of ultraprocessed food (UPF) consumption on metabolic disorders (e.g., adiposity, metabolic associated steatotic liver disease [MASLD], and insulin resistance) in children and adolescents with obesity to improve dietary guidelines and public health strategies. Methods: The dietary intake of 149 participants (aged 8–17 years) was assessed with food diaries. The NOVA classification system was used to classify food according to the degree of processing. Metabolic outcomes, including the fat mass index (FMI), hepatic fat percentage, and insulin resistance, were measured via dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging proton density fat fraction (MRI-PDFF), and biochemical analysis, respectively. Results: Greater UPF consumption from baseline to the 6-month follow-up was significantly associated with increased insulin and decreased total cholesterol and LDL-cholesterol. UPF consumption was positively associated with the prevalence of MASLD (liver MRI-PDFF ≥ 5%; odds ratio _{T3 vs. T1} = 1.75; 95% confidence interval [CI] 1.03, 3.00), moderate-to-severe MASLD (liver MRI-PDFF ≥ 10%; OR _{T3 vs. T1} = 4.19; 95% CI 1.72, 10.22), and insulin resistance (OR _{T3 vs. T1} = 2.44; 95% CI 1.33, 4.48), after adjusting for covariates. A linear dose-response relationship was observed between UPF consumption and the odds of moderate-to-severe MASLD and insulin resistance. Conclusions: Greater UPF consumption was strongly associated with MASLD and insulin resistance in children and adolescents with obesity, underscoring the importance of reducing UPF consumption through dietary guidelines and public health interventions to mitigate the risk of obesity-related metabolic conditions in young populations.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease. Despite intensive research, considerable information on NAFLD development remains elusive. In this study, we examined the effects of vitamin D on age-induced NAFLD, especially in connection with mitochondrial abnormalities. We observed the prevention of NAFLD in 22-month-old C57BL/6 mice fed a vitamin D₃-supplemented (20,000 IU/kg) diet compared with mice fed a control (1000 IU/kg) diet. We evaluated whether vitamin D₃ supplementation enhanced mitochondrial functions. We found that the level of mitochondrial contact site and cristae organizing system (MICOS) 60 (Mic60) level was reduced in aged mice, and this reduction was specifically restored by vitamin D₃. In addition, depletion of Immt, the human gene encoding the Mic60 protein, induced changes in gene expression patterns that led to fat accumulation in both HepG2 and primary hepatocytes, and these alterations were effectively prevented by vitamin D_3. In addition, silencing of the vitamin D receptor (VDR) decreased the Mic60 levels, which were recovered by vitamin D treatment. To assess whether VDR directly regulates Mic60 levels, we performed chromatin immunoprecipitation and reporter gene analysis. We discovered that VDR directly binds to the Immt 5’ promoter region spanning positions −3157 to −2323 and thereby upregulates Mic60. Our study provides the first demonstration that a reduction in Mic60 levels due to aging may be one of the mechanisms underlying the development of aging-associated NAFLD. In addition, vitamin D₃ could positively regulate Mic60 expression, and this may be one of the important mechanisms by which vitamin D could ameliorate age-induced NAFLD.

Age-related frailty and reduced physical activity contribute to a degenerative loss of muscle mass, function, and strength, which is known as sarcopenia. Increasing evidence has shown that vitamin D has beneficial effects on the muscle health. However, the molecular mechanisms of vitamin D have not been fully elucidated. In this study, we aimed to demonstrate whether vitamin D can overcome muscle atrophy due to aging, especially with respect to the regulation of myokines. Young (3-month-old) and aged (18-month-old) C57BL/6 mice were assigned to the following 3 groups: normal diet (1000 IU/kg), vitamin D₃-supplemented diet (20,000 IU/kg), and normal diet plus exercise for 4 months. We found that the reduction in muscle strength and mass due to aging was reversed by vitamin D₃ supplementation. The levels of markers involved in muscle atrophy and cellular senescence in the muscle of the aged mice were substantially decreased by vitamin D₃. Interestingly, we observed that the expression of apelin and its receptor (APJ), which is known to be secreted after exercise, significantly increased in aged muscles with a vitamin D₃-supplemented diet but not in the young mice. Moreover, circulating interleukin-6 (IL-6) and growth differentiation factor 8 (GDF8) levels were significantly increased in the aged mice but were restored by vitamin D₃ treatment. Our present data indicate that vitamin D₃ supplementation ameliorates aging-induced muscle atrophy and senescence, similar to the effects of exercise, suggesting the positive impact of vitamin D as an intervention strategy to prevent aging-induced metabolic diseases.

Muscle atrophy is closely associated with many diseases, including diabetes and cardiac failure. Growing evidence has shown that mitochondrial dysfunction is related to muscle atrophy; however, the underlying mechanisms are still unclear. To elucidate how mitochondrial dysfunction causes muscle atrophy, we used hindlimb‐immobilized mice. Mitochondrial function is optimized by balancing mitochondrial dynamics, and we observed that this balance shifted towards mitochondrial fission and that MuRF1 and atrogin‐1 expression levels were elevated in these mice. We also found that the expression of yeast mitochondrial escape 1‐like ATPase (Yme1L), a mitochondrial AAA protease was significantly reduced both in hindlimb‐immobilized mice and carbonyl cyanide m‐chlorophenylhydrazone (CCCP)‐treated C2C12 myotubes. When Yme1L was depleted in myotubes, the short form of optic atrophy 1 (Opa1) accumulated, leading to mitochondrial fragmentation. Moreover, a loss of Yme1L, but not of LonP1, activated AMPK and FoxO3a and concomitantly increased MuRF1 in C2C12 myotubes. Intriguingly, the expression of myostatin, a myokine responsible for muscle protein degradation, was significantly increased by the transient knock‐down of Yme1L. Taken together, our results suggest that a deficiency in Yme1L and the consequential imbalance in mitochondrial dynamics result in the activation of FoxO3a and myostatin, which contribute to the pathological state of muscle atrophy.

Background/Objectives: Childhood overweight/obesity status is a critical risk factor for adverse cardiometabolic outcomes. We aimed to evaluate the sex-specific associations between a maintained childhood overweight status and late-adolescent cardiometabolic risk factors using data from a Korean longitudinal study. Methods: We used data from the Korean Children-Adolescents Study, a prospective cohort of children enrolled at age 7 and followed annually from 2005 to 2020. Among participants who were followed at least once, a total of 899 children (438 boys, 461 girls) with consistent body mass index (BMI) status at ages 7–9 and 10–12 were included in the analysis. Participants were categorized into two groups on the basis of BMI: normal weight maintenance and overweight maintenance. Multivariable linear regression was used to examine the associations between BMI patterns and cardiometabolic risk factors, with adjustments for covariates. Results: Among the 899 children (mean age: 7.1 ± 0.4 years, 48.7% boys), 12.8% of boys and 5.9% of girls were classified into the overweight maintenance group. Boys in the overweight maintenance group had significantly greater BMIs, waist circumferences (WC), body fat percentages, trunk fat mass, and aspartate aminotransferase and alanine aminotransferase levels at ages 15 and 18. Girls in the same group had elevated BMI, WC, body fat percentage, trunk fat mass, and blood pressure and experienced earlier pubertal onset. Conclusions: Maintaining an overweight status during childhood is associated with adverse cardiometabolic profiles in adolescence, with sex-specific differences. These findings highlight the importance of early, sex-specific interventions to prevent long-term health risks associated with childhood obesity.