lifestyle related diseases
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Worldwide prevalence of obesity is associated with the increase of lifestyle-related diseases. The accumulation of intermuscular adipose tissue (IMAT) is considered a major problem whereby obesity leads to sarcopenia and metabolic disorders and thus is a promising target for treating these pathological conditions. However, whereas obesity-associated IMAT is suggested to originate from PDGFRα+ mesenchymal progenitors, processes underlying their adipogenesis remain largely unexplored. Here, we comprehensively investigated intra- and extracellular changes associated with these processes using single-cell RNA sequencing (scRNA-Seq) and mass spectrometry. Our scRNA-Seq analysis identified a small PDGFRα+ cell population in obese mice directed strongly toward adipogenesis. Proteomic analysis showed that the appearance of this cell population is accompanied by an increase in galectin-3 in interstitial environments, which was found to activate adipogenic PPARγ signals in PDGFRα+ cells. Moreover, IMAT formation during muscle regeneration was significantly suppressed in galectin-3 KO mice. Our findings, together with these multi-omics datasets, could unravel microenvironmental networks during muscle regeneration highlighting possible therapeutic targets against IMAT formation in obesity.

AbstractRecent studies have demonstrated the association of altered epigenomes with lifestyle-related diseases. Epigenetic regulation promotes biological plasticity in response to environmental changes, and such plasticity may cause a ‘memory effect’, a sustained effect of transient treatment or an insult in the course of lifestyle-related diseases. We investigated the significance of epigenetic changes in several genes required for renal integrity, including the nephrin gene in podocytes, and the sustained anti-proteinuric effect, focusing on the transcription factor Krüppel-like factor 4 (KLF4). We further reported the role of the DNA repair factor lysine-acetyl transferase 5 (KAT5), which acts coordinately with KLF4, in podocyte injury caused by a hyperglycemic state through the acceleration of DNA damage and epigenetic alteration. In contrast, KAT5 in proximal tubular cells prevents acute kidney injury via glomerular filtration regulation by an epigenetic mechanism as well as promotion of DNA repair, indicating the cell type-specific action and roles of DNA repair factors. This review summarizes epigenetic alterations in kidney diseases, especially DNA methylation, and their utility as markers and potential therapeutic targets. Focusing on transcription factors or DNA damage repair factors associated with epigenetic changes may be meaningful due to their cell-specific expression or action. We believe that a better understanding of epigenetic alterations in the kidney will lead to the development of a novel strategy for chronic kidney disease (CKD) treatment.

Background: Movement restrictions during the coronavirus disease 2019 (COVID-19) pandemic have inflicted stress and affected drinking behavior. However, limited information is available on the changes in alcohol use among the Japanese population.Method: This retrospective study included 371 subjects aged 20–74 years who underwent medical checkups at Fuyoukai Murakami Hospital before (April 1, 2019 to December 31, 2019) and during the COVID-19 pandemic (April 1, 2020 to May 31, 2020). All data were extracted from medical records. Changes in alcohol consumption and severity were also investigated. A logistic regression model was used to identify the risk factors associated with increased drinking, and seven variables were sequentially introduced into the model—age (≤ 49 years), male sex, prior instructions for alcohol restriction, medication for lifestyle-related diseases (e.g., hypertension, dyslipidemia, type 2 diabetes mellitus, and hyperuricemia), depression or insomnia, essential workers, and smoking.Results: The median age was 46 years, and 81.7% subjects were men. In total, 25.1% subjects increased their alcohol intake, and 24.5% subjects reduced their alcohol intake. The rates of excessive alcohol consumption (≥ 60 g ethanol per day) were 15.9% and 16.7% in the pre-COVID-19 period and during the COVID-19 pandemic, respectively. Multivariate analysis identified only age ≤ 49 years as a risk factor for increased drinking (adjusted odds ratio, 2.20; 95% confidence interval, 1.22–3.99; p = 0.009).Conclusion: Approximately one-fourth of the subjects reported increased drinking, although the overall severity remained stable. The importance of alcohol reduction, particularly among young people, should be emphasized.

Humans usually get dietary carotenoids from foods such as green and yellow vegetables and algae. Carotenoids have been reported to effectively reduce the risk of developing lifestyle-related diseases. β-Cryptoxanthin, which is an antioxidative carotenoid and a type of provitamin A, is metabolically converted to vitamin A. β-Cryptoxanthin has recently gained attention for its risk-reducing effects on lifestyle-related diseases, especially on non-alcoholic fatty liver disease (NAFLD), from epidemiological, interventional, and mechanistic studies. Retinoids (vitamin A) have also been reported to be useful as a therapeutic agent for NAFLD. Provitamin A is known to serve as a supply source of retinoids through metabolic conversion by the regulated activity of β-carotene 15,15′-monooxygenase 1 (BCMO1) to the retina only when retinoids are deficient. From mechanistic studies using NAFLD-model mice, β-cryptoxanthin has been shown to contribute to the improvement of NAFLD through a multifaceted approach, including improved insulin resistance, suppression of oxidative stress and inflammation, a reduction of macrophages and a shift of their subsets, and control of lipid metabolism by peroxisome proliferator-activated receptor (PPAR) family activation, which are also expected to have clinical applications. β-Cryptoxanthin has the potential to prevent lifestyle-related diseases from different angles, not only as an antioxidant but also as a retinoid precursor.

Based on the results of a previous WHO-CARDIAC study, this study was designed to test the effect of the daily consumption of a diet rich in potassium with optimal salt content, rich in fish meat and soy isoflavones, corresponding to the ingredients of a traditional Japanese diet. The test meals were a Balanced Lunch (BL) with chicken as the main dish and a Fortified Lunch (FL) with fish and soy as the main dish, which appeared the same. A double-blind, randomized controlled trial was conducted in 64 relatively obese men (47.2 ± 5.5 years old) who consumed the lunch at their work site for 4 weeks. All participants underwent fasting blood sampling, 24-h urine collection, as well as measurements of height, weight, and blood pressure before and after the intervention. Body mass index, blood pressure, and HbA1c were significantly improved and a 3-g reduction of salt intake was proven by 24-h urine collection in both groups. Moreover, HDL cholesterol and the Atherogenic Index (AI) were significantly improved in the FL group. In conclusion, the risks of lifestyle-related diseases in working men were reduced by one meal per day intervention of optimally-salted traditional Japanese diets containing soy and fish nutrients with high vegetable ingredients.

An enzyme-linked immunosorbent assay (ELISA) can be used for quantitative measurement of proteins, and improving the detection sensitivity to the ultrasensitive level would facilitate the diagnosis of various diseases. In the present review article, we first define the term ‘ultrasensitive’. We follow this with a survey and discussion of the current literature regarding modified ELISA methods with ultrasensitive detection and their application for diagnosis. Finally, we introduce our own newly devised system for ultrasensitive ELISA combined with thionicotinamide adenine dinucleotide cycling and its application for the diagnosis of infectious diseases and lifestyle-related diseases. The aim of the present article is to expand the application of ultrasensitive ELISAs in the medical and biological fields.

AbstractThe aim of this study was to clarify risk factors for esophageal candidiasis (EC) in immunocompetent patients in a community hospital. 7736 patients who underwent esophagogastroduodenoscopy at our hospital from April 2012 to July 2018 were enrolled. The relationships between EC and the following factors: age, gender, body mass index, lifestyle, lifestyle-related diseases, medication, and endoscopic findings were analyzed. EC was observed in 184 of 7736 cases (2.4% morbidity rate). Multivariate analysis revealed that significant risk factors for the development of EC were: diabetes mellitus {odds ratio (OR): 1.52}, proton pump inhibitor (PPI) use (OR: 1.69), atrophic gastritis (AG) (OR: 1.60), advanced gastric cancer (OR: 4.66), and gastrectomy (OR: 2.32). When severe EC (Kodsi grade ≥ II) was compared to mild EC (grade I), the most significant risk factors were advanced gastric cancer (OR: 17.6) and gastrectomy (OR: 23.4). When considering the risk of AG and PPI use with EC development, the risk increased as follows: AG (OR: 1.59), PPI use (OR: 2.25), and both (OR: 3.13). PPI use, AG, advanced gastric cancer and post-gastrectomy are critical risk factors for the development of EC. We suggest close monitoring for EC development when PPIs are administered to patients with these factors.

Purpose: Quercetin has been reported as a more potent inhibitor of fat accumulation than other flavonoids. However, little information is available regarding the strength and mechanism of the repressive action of luteolin on fat accumulation. Therefore, the aim of the present study was to evaluate the comparative effects of luteolin and quercetin on the differentiation of 3T3-L1 preadipocytes into mature adipocytes. Methods: 3T3-L1 preadipocytes were differentiated by treatment with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine in the presence of luteolin or quercetin. Alterations in triacylglycerol (TG) levels, lipid-filled adipocyte quantity, and the mRNA and protein expression levels of CCAAT-enhancer-binding protein α (C/EBPα) and peroxisome proliferator–activated receptor γ (PPARγ) were measured. Results: Both luteolin and quercetin reduced TG levels, the number of lipid-filled adipocytes, and the mRNA expression levels of C/EBPα and PPARγ; however, these effects occurred with lower concentrations of luteolin than quercetin. Conclusions: These results suggest that luteolin may be more potent than quercetin in inhibiting adipocyte differentiation. These effects may be explained by differences in the inhibitory effects of the two compounds on C/EBPα and PPARγ expression. This study suggests that luteolin might be a beneficial dietary supplement for obesity and lifestyle-related diseases.

Rapid postprandial blood glucose elevation can cause lifestyle-related diseases, such as type II diabetes. The absorption of food-derived glucose is primarily mediated by sodium/glucose cotransporter 1 (SGLT1). Moderate SGLT1 inhibition can help attenuate postprandial blood glucose elevation and prevent lifestyle-related diseases. In this study, we established a CHO cell line stably expressing human SGLT1 and examined the effects of phytochemicals on SGLT1 activity. Among the 50 phytochemicals assessed, tangeretin and cardamonin inhibited SGLT1 activity. Tangeretin and cardamonin did not affect the uptake of L-leucine, L-glutamate, and glycyl-sarcosine. Tangeretin, but not cardamonin, inhibited fructose uptake, suggesting that the inhibitory effect of tangeretin was specific to the monosaccharide transporter, whereas that of cardamonin was specific to SGLT1. Kinetic analysis suggested that the suppression of SGLT1 activity by tangeretin was associated with a reduction in Vmax and an increase in Km, whereas suppression by cardamonin was associated with a reduction in Vmax and no change in Km. Oral glucose tolerance tests in mice showed that tangeretin and cardamonin significantly suppressed the rapid increase in blood glucose levels. In conclusion, tangeretin and cardamonin were shown to inhibit SGLT1 activity in vitro and lower blood glucose level in vivo.