Keywords: Chronic kidney disease; Hepatocellular carcinoma; Hepatic resection Author Affiliation: (1) Department of General and Gastroenterological Surgery, Osaka Medical College Mishima-Minami ...Hospital, 8-1 Tamagawa-shinmachi, 569-0856, Takatsuki City, Osaka, Japan (2) Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, 2-7 Daigaku-machi, 569-8686, Takatsuki City, Osaka, Japan (3) Second Department of Internal Medicine, Osaka Medical College Hospital, 2-7 Daigaku-machi, 569-8686, Takatsuki City, Osaka, Japan (4) Department of Internal Medicine, Osaka Medical College Mishima-Minami Hospital, 8-1 Tamagawa-shinmachi, 569-0856, Takatsuki City, Osaka, Japan (a) sur129@osaka-med.ac.jp Article History: Registration Date: 10/18/2020 Received Date: 04/12/2020 Accepted Date: 10/17/2020 Online Date: 10/27/2020 Byline:
We sought to investigate the relationship between insulin resistance (IR) and body composition as assessed by bioelectrical impedance analysis in Japanese health check-up recipients (1186 men and ...1441 women). IR was defined as a Homeostasis Model Assessment of IR (HOMA-IR) ≥ 2.5. In body-composition-related parameters, the fat mass index (F index) was defined as fat mass divided by the height squared (kg/m2). The fat-free mass index (FF index) was defined as fat-free mass divided by the height squared (kg/m2). The F index to FF index ratio (F-FF ratio) was defined as the F index divided by the FF index. Factors related to HOMA-IR were examined. The median HOMA-IR was 1.54 in men and 1.30 in women (p < 0.0001). The median F index was 4.9 kg/m2 in men and 6.1 kg/m2 in women (p < 0.0001). The median FF index was 18.2 kg/m2 in men and 15.1 kg/m2 in women (p < 0.0001). The median F-FF ratio was 0.272 in men and 0.405 in women (p < 0.0001). The F-FF ratio was an independent factor associated with HOMA-IR in the multivariate analysis in both genders, while the F index and FF index were not in both genders. In conclusion, fat and skeletal muscle balance can be controlled by IR in Japanese adults.
Epoxyxanthophylls (epoxide-containing xanthophylls), a group of carotenoids, are ubiquitously distributed in edible plants. Among them, neoxanthin in green leafy vegetables and fucoxanthin in brown ...algae have been reported to exhibit an antiproliferative effect on several human cancer cells in vitro. However, there is little information about the intestinal absorption and metabolic fate of dietary epoxyxanthophylls in humans. To estimate the intestinal absorption of neoxanthin and fucoxanthin in humans, we evaluated the plasma epoxyxanthophyll concentrations before and after 1-week dietary interventions with spinach (Spinacia oleracea) and wakame (Undaria pinnatifida). The epoxyxanthophylls and their metabolites in the plasma extracts were determined by HPLC after partial purification and concentration with solid-phase extraction cartridges. Even after 1 week of spinach intake (3·0 mg neoxanthin/d), the plasma concentrations of neoxanthin and its metabolites (neochrome stereoisomers) remained very low (about 1 nmol/l), whereas those of β-carotene and lutein were markedly increased. Similarly, the plasma concentration of fucoxanthinol, a gastrointestinal metabolite of fucoxanthin, was < 1 nmol/l after 1 week of wakame intake (6·1 mg fucoxanthin/d). These results indicated that the plasma response to dietary epoxyxanthophylls was very low in humans even after 1-week intake of epoxyxanthophyll-rich diets.
Background and Aims
Real‐world data for treatment effectiveness and renal outcomes in chronic hepatitis B (CHB) patients who were switched to the new and safer prodrug tenofovir alafenamide (TAF) ...from tenofovir disoproxil fumarate (TDF) are limited. Therefore, we aimed to evaluate treatment and renal outcomes of this population.
Approach and Results
We analyzed 834 patients with CHB previously treated with TDF for ≥12 months who were switched to TAF in routine practice at 13 US and Asian centers for changes in viral (HBV DNA < 20 IU/mL), biochemical (alanine aminotransferase ALT < 35/25 U/L for male/female), and complete (viral+biochemical) responses, as well as estimated glomerular filtration rate (eGFR; milliliters per minute per 1.73 square meters) up to 96 weeks after switch. Viral suppression (P < 0.001) and ALT normalization (P = 0.003) rates increased significantly after switch, with a trend for increasing complete response (Ptrend = 0.004), while the eGFR trend (Ptrend > 0.44) or mean eGFR (P > 0.83, adjusted for age, sex, baseline eGFR, and diabetes, hypertension, or cirrhosis by generalized linear modeling) remained stable. However, among those with baseline eGFR < 90 (chronic kidney disease CKD stage ≥2), mean eGFR decreased significantly while on TDF (P = 0.029) but not after TAF switch (P = 0.90). By week 96, 21% (55/267) of patients with CKD stage 2 at switch improved to stage 1 and 35% (30/85) of CKD stage 3‐5 patients improved to stage 2 and 1.2% (1/85) to stage 1.
Conclusions
Overall, we observed continued improvement in virologic response, ALT normalization, and no significant changes in eGFR following switch to TAF from TDF.
The increase in the number of patients with diabetes has become a worldwide healthcare issue, with numbers predicted to reach approximately 600 million by 2035. In Asia-Pacific region, the prevalence ...of type 2 diabetes has increased dramatically in recent decades, of which the major causes are believed to be modern lifestyle changes, e.g., Western dietary pattern and reduced physical activity, on their genetic basis of lower insulin secretory capacity. Particularly, in East Asian countries, the amount of fat intake has increased nearly three-fold over this half of century; dietary fat appears to be the major culprit of type 2 diabetes pandemic in East Asia. However, convincing evidence has not yet been provided as to whether high-fat diet causes type 2 diabetes in epidemiological cohort studies. Here, we summarize clinical studies regarding fat intake and type 2 diabetes, and animal studies on high-fat diet-induced diabetes including our recent works on the novel mouse lines (selectively bred diet-induced glucose intolerance-prone SDG-P and -resistant SDG-R) to address the etiology of high-fat diet-induced diabetes. These epidemiological and experimental findings would provide further insight into the etiology of type 2 diabetes under the modern nutritional environment, namely in the context of increased fat intake.
Many people were forced to stay at home, including non-alcoholic steatohepatitis (NASH) patients, however it is unclear how this home-life has affected the prognosis of NASH. In this study, we ...examined the influences of living at home during the coronavirus disease 2019 (COVID-19) pandemic NASH patients. In this study, we compared the clinical parameters of NASH patients without COVID-19 infection 3 months before with those 3 months after the declaration of a state of emergency. In the results, the changes of aspartate transaminase and alanine aminotransferase in the 3 months before (aspartate transaminase, –3.6 ± 13.8 U/L; alanine aminotransferase, –6.8 ± 19.5 U/L) was significantly exacerbated in the 3 months after (aspartate transaminase, 2.3 ± 7.5 U/L; alanine aminotransferase, 1.7 ± 10.4 U/L). Furthermore, the changes of the fibrosis-4 index in the 3 months before (–0.27 ± 0.84) was also significantly exacerbated in the 3 months after (0.38 ± 0.96). In conclusion, liver dysfunctions in NASH patients were exacerbated due to the emergency declaration and outing restriction which accompanied COVID-19.
To identify the upstream signaling of aluminum-induced malate secretion through aluminum-activated malate transporter 1 (AtALMT1), a pharmacological assay using inhibitors of human signal ...transduction pathways was performed. Early aluminum-induced transcription of AtALMT1 and other aluminum-responsive genes was significantly suppressed by phosphatidylinositol 4-kinase (PI4K) and phospholipase C (PLC) inhibitors, indicating that the PI4K-PLC metabolic pathway activates early aluminum signaling. Inhibitors of phosphatidylinositol 3-kinase (PI3K) and PI4K reduced aluminum-activated malate transport by AtALMT1, suggesting that both the PI3K and PI4K metabolic pathways regulate this process. These results were validated using T-DNA insertion mutants of PI4K and PI3K-RNAi lines. A human protein kinase inhibitor, putatively inhibiting homologous calcineurin B-like protein-interacting protein kinase and/or Ca-dependent protein kinase in Arabidopsis, suppressed late-phase aluminum-induced expression of AtALMT1, which was concomitant with the induction of an AtALMT1 repressor, WRKY46, and suppression of an AtALMT1 activator, Calmodulin-binding transcription activator 2 (CAMTA2). In addition, a human deubiquitinase inhibitor suppressed aluminum-activated malate transport, suggesting that deubiquitinases can regulate this process. We also found a reduction of aluminum-induced citrate secretion in tobacco by applying inhibitors of PI3K and PI4K. Taken together, our results indicated that phosphatidylinositol metabolism regulates organic acid secretion in plants under aluminum stress.
A number of epidemiological studies demonstrated that postprandial hyperglycemia is a risk factor for cardiovascular disease in individuals with impaired glucose tolerance. Although several ...laboratory studies have addressed the plausible causal role of postprandial acute hyperglycemia (glucose spikes) in the development of atherosclerosis, there is little convincing evidence in vivo whether the atherosclerotic lesion formation can be accelerated solely by glucose spikes. Here, we assessed the effect of repetitive glucose spikes on atherosclerotic lesion formation in mice.
Female C57BL/6 mice were fed an atherogenic diet from 8 to 28 weeks of age. During the atherogenic diet feeding period, the mice orally received a glucose solution (50 mg glucose/mouse; G group) or water (W group) twice daily, 6 days a week. Atherosclerotic lesion formation in the aortic sinus was quantitatively analyzed in serial cross-sections by oil red O staining.
G group mice showed transient increases in blood glucose level (~5 mmol/L above W group), and the levels returned to levels similar to those in W group mice within 60 min. No significant differences in glucose tolerance, insulin sensitivity, and plasma lipid profiles were observed after the 20-week repetitive administration between the 2 groups. G group mice showed an approximately 4-fold greater atherosclerotic lesion size in the aortic sinus than W group mice. Gene expression levels of Cd68 and Icam1 in the thoracic aorta were higher in G group mice than in W group mice.
These results indicate that glucose spikes can accelerate atherosclerotic lesion formation, with little influence on other metabolic disorders. Repetitive glucose administration in wild-type mice may serve as a simple and useful approach to better understanding the causal role of glycemic spikes in the development of atherosclerosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Malnutrition is a major contributor to muscle loss and muscle dysfunction, known as sarcopenia. Malnutrition is common in patients with inflammatory bowel disease (IBD). IBD includes ulcerative ...colitis (UC) and Crohn’s disease (CD). The number of patients with IBD has recently been increasing. More severe malnutrition is often seen in CD compared to UC, probably due to CD affecting the main site of nutrient absorption, extensive mucosal lesions, fistulas, short bowel syndrome after resection, or obstruction of the gastrointestinal tract. A recent meta-analysis showed the high prevalence of sarcopenia in patients with IBD, and thus sarcopenia is a very important problem for IBD. Although IBD is more common in younger patients, sarcopenia can develop through a variety of mechanisms, including malnutrition, chronic inflammation, increased inflammatory status in adipose tissue, vitamin deficiency, and imbalance of the muscle–gut axis. In addition, sarcopenia has a negative impact on postoperative complications and hospital stay in patients with IBD. Appropriate intervention for sarcopenia may be important, in addition to clinical remission and endoscopic mucosal healing in patients with IBD. Much more attention will thus be paid to sarcopenia in patients with IBD. In this review, we outline IBD and sarcopenia, based on the current evidence.
Nonalcoholic fatty liver disease (NAFLD) can develop into end-stage disease that includes cryptogenic cirrhosis and hepatocellular carcinoma. Bacterial endotoxin, for example lipopolysaccharide ...(LPS), plays an important role in the pathogenesis of NAFLD. The aim of this study was to assess the role of LPS in the development of NAFLD. Twenty-one male Zucker (fa/fa) rats were divided into three groups: rats fed for twelve weeks on a diet rich in disaccharide (D12 group), rats similarly managed but treated with LPS (LPS group), and those on the same diet for 24 weeks (D24 group). Histological examination demonstrated that this protocol induced hepatic steatosis in the LPS and D24 groups. Significant, marked accumulation of lipid droplets was observed in the LPS group, compared with the D24 group. Rats from the LPS group showed a decrease in plasma adiponectin levels, an increase in plasma leptin levels, and greater expression of FAS and SREBP-1c mRNA in the liver, compared with rats from the D24 group. These finding coincided with histological findings. We therefore suggest that LPS may accelerate the progression of hepatic steatosis.
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