The prevalence of fatty liver in children is unknown and its relationship to obesity is poorly defined. The present study of 810 northern Japanese children (4-12 years old) determined the prevalence of fatty liver in the pediatric population and its relationship to obesity. Diagnosis of fatty liver was based on established real-time ultrasonographic criteria. The overall prevalence of fatty liver was 2.6% and was higher for boys (3.4%) than for girls (1.8%), although not statistically significant (P = 0.15). Fatty liver was found in children as young as 6 years of age. There was no significant association between the prevalence of fatty liver and height (physical growth). There was a strong positive correlation between fatty liver prevalence and established obesity indices: Rohrer's Index--chi 2 linear trend = 59.2, P < 0.0001; body mass index--chi 2 linear trend = 91.6, P < 0.0001; and age-gender-adjusted Japanese standard index of weight for height--chi 2 linear trend = 93.2, P < 0.0001. However, direct measurement of abdominal subcutaneous fat thickness by ultrasonography was the best predictor of fatty liver: chi 2 linear trend = 159, P < 0.0001. These results indicate that fatty liver may develop very early in life, and there is a direct relationship between degree of obesity and fatty liver in children.
Aging is broadly defined as the functional decline that occurs in all body systems. The accumulation of senescent cells is considered a hallmark of aging and thought to contribute to the aging pathologies. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that regulates a myriad of cellular processes and has important roles in embryonic development, physiological tissue homeostasis, and various pathological conditions. TGF-β exerts potent growth inhibitory activities in various cell types, and multiple growth regulatory mechanisms have reportedly been linked to the phenotypes of cellular senescence and stem cell aging in previous studies. In addition, accumulated evidence has indicated a multifaceted association between TGF-β signaling and aging-associated disorders, including Alzheimer’s disease, muscle atrophy, and obesity. The findings regarding these diseases suggest that the impairment of TGF-β signaling in certain cell types and the upregulation of TGF-β ligands contribute to cell degeneration, tissue fibrosis, inflammation, decreased regeneration capacity, and metabolic malfunction. While the biological roles of TGF-β depend highly on cell types and cellular contexts, aging-associated changes are an important additional context which warrants further investigation to better understand the involvement in various diseases and develop therapeutic options. The present review summarizes the relationships between TGF-β signaling and cellular senescence, stem cell aging, and aging-related diseases.
This study was conducted to determine if there is an association between shift work and risk factors for coronary heart disease (CHD) in Japanese male blue-collar shift workers. Health check-up data on serum lipid concentration and anthropometric indices of 33 three-shift workers and 27 two-shift workers were compared with those of day workers. The average years in age of the shift workers and day workers were 34.5 (SD = 7.1) and 32.7 (SD = 7.6), respectively. Serum total cholesterol levels of three-shift, two-shift and day workers were 5.70 (SD = 1.19) mmol/l, 4.81 (SD = 1.01) mmol/l, 4.98 (SD = 0.95) mmol/l, respectively, and the cholesterol levels of three-shift workers were significantly higher than the other workers (p < 0.05). In addition, the abdominal to hip circumference ratios were 0.905 (SD = 0.060) for three-shift workers and 0.877 (SD = 0.054) for day workers, with a significant difference (p < 0.05). In the present Japanese population, three-shift workers had higher risks of CHD than day workers, which was characterized by higher levels of serum total cholesterol and tendency to central obesity. These findings held when lifestyle factors were taken into account.
Retinoblastoma (RB) protein inactivation during tumor progression is often associated with acquisition of immature phenotypes and resistance to therapy. Determination of an RB inactivation signature in a context of gaining undifferentiated phenotype in a p53-null sarcoma system revealed a critical role for interleukin (IL)-6. Using a Gene Set Enrichment Analysis (GSEA), we discovered that poorly differentiated breast cancers are enriched for this RB inactivation signature. Accelerated IL-6 secretion following RB inactivation in an RB-intact luminal-type breast cancer cell line MCF-7 promoted a positive feed forward loop between IL-6 and STAT3 driving tumor growth and endocrine therapy resistance. In addition, some of RB-intact basal-like type breast cancer cell lines exhibited a similar phenotype following RB depletion. The mechanism whereby RB inactivation increases IL-6 production in MCF-7 cells appeared to involve fatty acid oxidation (FAO)-dependent mitochondrial metabolism and c-Jun NH(2)-terminal kinase (JNK). In addition, IL-6, via STAT3-mediated feedback to mitochondria, autonomously adjusts mitochondrial superoxide to levels suitable to maintain stem cell-like activity. The gene expression profile of luminal-type breast cancer patients with low RB expression revealed high enrichment of genes involved in mitochondrial respiration and downstream targets of IL-6. These findings unveiled an unexpected strategy whereby RB suppresses malignant features of cancer cells through metabolic reprogramming and cell-autonomous inflammation.
Objectives To investigate the prevalence of non-alcoholic fatty liver disease (NAFLD) in children and its relationship to metabolic syndrome, insulin resistance, and waist circumference (WC). Methods This was a population-based cross-sectional, case-control study. Cases were selected among students of a primary and junior high school, respectively, and ageand sex-matched control subjects were selected randomly (ratio of cases to control subject was 37:113). Results Of the 846 students, aged between 6 and 15 years, enrolled in the study and screened by ultrasonography, 37 children were diagnosed as having NAFLD (score C 1). There was a significant sex difference in the prevalence of NAFLD(P = 0.003). The trend test revealed a strong doseresponse relationship (P \ 0.001) between pediatric NA-FLD and the number of the proposed components of pediatric metabolic syndrome in Japan (MetS-JC), such as a clustering of the components of MetS-JC. Additionally, the linear trend of the odds ratios (ORs) with increasing percentile of the homeostasis model assessmentinsulin resistance (HOMA-IR) was statistically significant (P \ 0.001). However, when WC was added to the logistic model, the ORs were no longer significant, whereas WC turned out to be an independent risk factor for NAFLD regardless of the HOMA-IR index. Conclusion The prevalence of NAFLD in children and adolescents is closely related to metabolic syndrome, insulin resistance, and WC.
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