益生菌干预合并糖调节受损的非酒精性脂肪肝病的疗效分析

目的观察益生菌对非酒精性脂肪肝病(NAFLD)合并糖调节受损(IGR)患者的临床疗效。方法采用随机、对照、双盲的研究方法将120例合并IGR的NAFLD患者随机分为观察组和对照组,观察组口服多烯磷脂酰胆碱及益生菌力存颗粒,对照组仅服用多烯磷脂酰胆碱。3个月后观察指标变化(ALT、AST、GGT、TC、TG、LDL、HDL、FBG、2hPG、HbA1c)、身高体重指数(BMI)及胰岛素抵抗指数(HOMA-IR)变化情况,统计临床疗效。结果两组患者的肝功能、脂代谢紊乱情况(ALT、AST、GGT、TC、TG、LDL、HDL)均有不同程度改善(两组患者治疗前后比较,P0.05),但观察组肝功及脂代谢紊乱改善更为明显,与对照组相比有统计学意义(P0.05),且治疗后观察组FBG、2hPG、HbA1c、BMI与HOMA-IR水平明显改善(P0.05),对照组差异无统计学意义(P0.05)。结论相对于多烯磷脂酰胆碱单药保肝治疗,益生菌联合治疗可更加显著的改善脂代谢及肝功能,同时可明显改善NAFLD合并IGR患者的糖代谢,加用益生菌治疗此类患者有积极的意义。     

Association between circulating inflammatory molecules and alcoholic liver disease in men

The association between alcoholic liver disease (ALD) and the inflammatory response remains controversial. The aim of this study was to explore this association between ALD and inflammation. We enrolled 214 male participants, who were divided into three age-matched groups: ALD (n?=?135), chronic alcohol ingestion without ALD (non-ALD; n?=?42), and control (n?=?37). The BMI was significantly higher in the ALD group than in the non-ALD and control groups (all P?=?0.000). Further, the constituent ratio of the liver inflammatory level was significantly higher in the ALD group than in the non-ALD and control groups (P?=?0.002 and P?=?0.000, respectively). In addition, the median serum ALT, AST, and GGT levels were significantly higher in the ALD group than in the control group (P?=?0.023, P?=?0.008, and P?=?0.000, respectively); these levels were also significantly higher in the ALD group than in the non-ALD group (P?=?0.013, P?=?0.010, and P?=?0.000, respectively). The median serum CRP level was significantly higher in the ALD group than in the non-ALD and control groups (P?=?0.006 and P?=?0.000, respectively). Further, the median serum TNF-α level was significantly lower in the ALD group than in the non-ALD and control groups (P?=?0.004 and P?=?0.000, respectively). The median serum sOX40L and HSP70 levels were significantly lower in the ALD group than in the control group (P?=?0.008 and P?=?0.018, respectively). In addition, the ALT, AST, and GGT levels were positively correlated with the CRP level (r?=?0.211, P?=?0.002; r?=?0.220, P?=?0.001 and r?=?0.295, P?=?0.000, respectively), and the GGT level was negatively correlated with the TNF-α (r?=??0.225, P?=?0.001), sOX40L (r?=??0.165, P?=?0.016), and HSP70 levels (r?=??0.178, P?=?0.009). Further, the Cr level was negatively correlated with the IL-10 level (r?=??0.166, P?=?0.015). Logistic regression analysis verified that the BMI (OR??=??1.637, 95%CI: 1.374–1.951, P??=??0.000) and GGT level were significantly higher (OR??=??1.039, 95%CI: 1.020–1.059, P??=??0.000) and that the TNF-α (OR??=??0.998, 95%CI: 0.996–1.000, P??=??0.030) and HSP70 levels were significantly lower (OR??=??1.017, 95%CI: 1.003–1.031, P??=??0.029) in the ALD group than in the non-ALD group. Further, the moderate-to-severe ALD patients had a significantly higher serum CRP level (Or?=???1.349, 95%CI: 1.066–1.702, P??=??0.013) and significantly lower HSP60 (OR??=??0.965, 95%CI: 0.938–0.993, P??=??0.014) and HSP70 levels (OR??=??0.978, 95%CI: 0.962–0.995, P??=??0.010) than the mild ALD patients. These results suggest that ALD patients may present with obesity, liver damage, and an imbalanced inflammatory immune response, mainly manifesting as decreased levels of immune inflammatory cytokines. In addition, they suggest that certain liver and kidney function parameters and ALD severity are either positively or negatively correlated with certain inflammatory cytokines. Hence, ALD patients may be at increased risks of obesity- and inflammation-related diseases. Accordingly, to control the inflammatory response, preventative measures for patients with this disease should include weight control and protection of liver and kidney function.     

Association of KCNJ11 with impaired glucose regulation in essential hypertension

KCNJ11 is one of the candidate genes for type 2 diabetes, confirmed by genome wide association study, but there are little data on the relationship between KCNJ11 and impaired glucose regulation in essential hypertension patients. To identify the effect of E23K and I337V in the KCNJ11 gene on susceptibility to impaired glucose regulation, we conducted a case control study in 1125 essential hypertension patients with or without impaired glucose regulation among a Han Chinese population. We also evaluated the impact of two SNPs on insulin sensitivity and glucose tolerance estimated through an oral glucose tolerance test. In our case control study, no association of E23K and I337V with impaired glucose regulation was found using any genotypic models. However, lysine carriers of E23K showed a significant association with decreased insulin (30 min) and Cederholm index, and valine carriers of I337V showed association with a lower Cederholm index. All the quantitative tests were performed by linear regression, with adjustment for gender, age, body mass index, blood pressure, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment. These findings provided evidence that the KCNJ11 gene plays a role in the pathogenesis of decreased insulin sensitivity in essential hypertension patients.     

Proteoglycan 4 deficiency protects against glucose intolerance and fatty liver disease in diet-induced obese mice

Objective

Proteoglycan 4 (Prg4) has emerged from human association studies as a possible factor contributing to weight gain, dyslipidemia and insulin resistance. In the current study, we investigated the causal role of Prg4 in controlling lipid and glucose metabolism in mice.

Association between non-alcoholic fatty liver disease with the susceptibility and outcome of COVID-19: A retrospective study

This study aims to evaluate the effect of non-alcoholic fatty liver disease (NAFLD) on the susceptibility and consequences of coronavirus disease 2019 (COVID-19). We retrospectively collected data from 218 adult COVID-19 patients who showed no evidence of excessive alcohol consumption and underwent abdominal ultrasound examinations. Of these patients, 39.4% patients had been diagnosed with NAFLD, which indicates a much higher prevalence of NAFLD than that reported in the general population. Significantly elevated white blood cell count (p = 0.008), alanine aminotransferase (p = 0.000), aspartate aminotransferase (p = 0.006) and C reactive protein (p = 0.012) were found in the patients with NAFLD. These patients also had significantly higher proportions of hypertension (p = 0.006) and diabetes (p = 0.049) than the non-NAFLD cases. No significant differences existed in the severity, mortality, viral shedding time and length of hospital stay between patients with or without NAFLD in the sample population. However, subgroup analyses found that in patients with normal body mass index (BMI), NAFLD sufferers were more likely to experience a severe event (30.0% vs 11.5%, p = 0.021). Kaplan-Meier curve (log-rank p = 0.017) and Cox regression (HR = 3.26, 95% CI: 1.17–9.04, p = 0.023) analyses confirmed that before and after adjusting for gender, age and comorbidities, NAFLD patients with normal BMI had a higher incidence of suffering severe events. People with NAFLD may have a higher proportion of COVID-19. NAFLD may be correlated with the severity of COVID-19 patients in the normal BMI group.     

Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease

Increased hepatocyte apoptosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and contributes to the profibrogenic state responsible for the progression to nonalcoholic steatohepatitis (NASH). Strategies aimed at reducing apoptosis may result in better outcomes for individuals with NAFLD. We therefore examined the effect of a short-term exercise program on markers of apoptosis-plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)-in 13 obese individuals with NAFLD [body mass index 35.2 ± 1.2 kg/m(2), >5% intrahepatic lipid (IHL) assessed by (1)H-MR spectroscopy]. Exercise consisted of treadmill walking for 60 min/day on 7 consecutive days at ～85% of maximal heart rate. Additionally, subjects underwent an oral glucose tolerance test and a maximal oxygen consumption (Vo(2max)) test before and after the exercise intervention. The Matsuda index was used to assess insulin sensitivity. We observed significant decreases in CK18 fragments (558.4 ± 106.8 vs. 323.4 ± 72.5 U/l, P < 0.01) and ALT (30.2 ± 5.1 vs. 24.3 ± 4.8 U/l, P < 0.05), and an increase in whole body fat oxidation (49.3 ± 6.1 vs. 69.4 ± 7.1 mg/min, P < 0.05), while decreases in circulating sFasL approached statistical significance (66.5 ± 6.0 vs. 63.0 ± 5.7 pg/ml, P = 0.06), as did the relationship between percent change in circulating CK18 fragments and ALT (r = 0.55, P = 0.05). We also observed a significant correlation between changes in fat oxidation and circulating sFasL (rho = -0.65, P < 0.05). There was no change in IHL following the intervention (18.2 ± 2.5 vs. 17.5 ± 2.1%, NS). We conclude that short-term exercise reduces a circulatory marker of hepatocyte apoptosis in obese individuals with NAFLD and propose that changes in the proapoptotic environment may be mediated through improved insulin sensitivity and increased oxidative capacity.     

Association between impaired glucose tolerance and circulating concentration of Lp(a) lipoprotein in relation to coronary heart disease.

OBJECTIVE--To examine whether impaired glucose tolerance and raised Lp(a) lipoprotein concentrations are associated in subjects with coronary artery disease. DESIGN--Study of two subject populations, one with and one without symptomatic coronary artery disease. Case-control analysis of patients with impaired glucose tolerance and normal glucose tolerance performed in each subject population independently. SETTING--A general practice and a hospital ward in Newcastle upon Tyne. SUBJECTS--517 apparently healthy subjects, 13 with impaired glucose tolerance, and 245 patients who had undergone coronary artery bypass graft surgery 12 months before, 51 with impaired glucose tolerance. MAIN OUTCOME MEASURES--Serum Lp(a) lipoprotein concentration, plasma glucose concentration before and after oral challenge with 75 g glucose monohydrate, and Lp(a) lipoprotein isoforms. RESULTS--In both the asymptomatic subjects and the subjects with coronary artery disease there was no significant difference between subjects with impaired glucose tolerance and subjects with normal and body mass index in serum Lp(a) lipoprotein concentrations (geometric mean 61 (geometric SD 4) mg/l v 83 (5) mg/l for asymptomatic subjects, 175 (3) v 197 (2) for subjects with heart disease), nor was there any difference in the proportion of subjects who had Lp(a) lipoprotein concentrations > 300 mg/l (31% v 23% for asymptomatic subjects, 37% v 37% for subjects with heart disease). For both subject groups there was no significant correlation between Lp(a) lipoprotein concentration and plasma glucose concentration after a glucose tolerance test, nor did Lp(a) lipoprotein concentration vary by quintile of glucose concentration after the test. Examination of Lp(a) lipoprotein isoforms in the subjects with coronary artery disease revealed an inverse relation between isoform size and plasma Lp(a) lipoprotein concentration, but there was no evidence that impaired glucose tolerance was associated with particular Lp(a) lipoprotein isoforms. CONCLUSION--Raised Lp(a) lipoprotein concentrations are not responsible for the association between impaired glucose tolerance and coronary artery disease.     

Calcium-dependent regulation of glucose homeostasis in the liver

A major role of the liver is to integrate multiple signals to maintain normal blood glucose levels. The balance between glucose storage and mobilization is primarily regulated by the counteracting effects of insulin and glucagon. However, numerous signals converge in the liver to ensure energy demand matches the physiological status of the organism. Many circulating hormones regulate glycogenolysis, gluconeogenesis and mitochondrial metabolism by calcium-dependent signaling mechanisms that manifest as cytosolic Ca²⁺ oscillations. Stimulus-strength is encoded in the Ca²⁺ oscillation frequency, and also by the range of intercellular Ca²⁺ wave propagation in the intact liver. In this article, we describe how Ca²⁺ oscillations and waves can regulate glucose output and oxidative metabolism in the intact liver; how multiple stimuli are decoded though Ca²⁺ signaling at the organ level, and the implications of Ca²⁺ signal dysregulation in diseases such as metabolic syndrome and non-alcoholic fatty liver disease.     

Association between light exposure at night and insomnia in the general elderly population: The HEIJO-KYO cohort

Chronic circadian misalignment between the internal and environmental rhythms, which is typically related to night-shift work and clock-gene variants, is associated with disruption of suprachiasmatic nucleus function and increased risk of insomnia. Under controlled laboratory conditions, light at night (LAN) suppresses melatonin secretion, delays the internal biological rhythm, and reduces sleepiness. Therefore, LAN exposure may cause circadian misalignment and insomnia, though it remains unclear in real-life situations whether LAN exposure is associated with insomnia. To evaluate an association between LAN exposure and sleep quality in home settings, we conducted a cross-sectional community-based study in 857 elderly individuals (mean age, 72.2 years). We evaluated bedroom light intensity using a light meter and subjectively and objectively measured sleep quality using the Pittsburgh Sleep Quality Index and an actigraph, respectively, along with urinary 6-sulfatoxymelatonin excretion. Compared with the lowest quartile group of LAN intensity, the highest quartile group revealed a significantly higher odds ratio (OR) for subjective insomnia in a multivariate model adjusted for age, gender, body mass index, daytime physical activity, urinary 6-sulfatoxymelatonin excretion, bedtime, rising time, and day length (adjusted OR, 1.61, 95% confidence interval, 1.05–2.45, p?=?0.029). In addition, higher OR for subjective insomnia was significantly associated with the increase in quartiles of LAN intensity (p_trend?=?0.043). Consistently, we observed significant association trends between the increase in quartiles of LAN intensity and poorer actigraphic sleep quality, including decreased sleep efficiency, prolonged sleep-onset latency, increased wake-after-sleep onset, shortened total sleep time, and delayed sleep-mid time in multivariate models adjusted for the covariates mentioned above (all p_trend?<?0.001). In conclusion, we demonstrated that LAN exposure in home settings is significantly associated with both subjectively and objectively measured sleep quality in a community-based elderly population.     

Interaction between insulin and estradiol in regulation of cardiac glucose and free fatty acid transporters

The estrogen binding to specific extranuclear receptors (ER) activates several intracellular pathways that are activated by insulin as well. Moreover, insulin and estradiol (E2) influence cardiac energy substrates, blood glucose and free fatty acids (FFAs), and both hormones exert cardio-beneficial effects. In view of these facts, we suggest that cross-talk between their signaling pathways might have an important role in regulation of cardiac energy substrate transport. Ovariectomized rats were treated with insulin, estradiol (E2), or their combination 20, 30, or 40?min before analysis of blood glucose and FFA level, as well as cardiac plasma membranes (PM) and low density microsomes (LDM) content of glucose (GLUT4 and GLUT1) and FFA (CD36) transporters. Insulin, given alone, or in combination with E2, decreased plasma glucose level at all time points, but did not influence FFA level, while E2 treatment itself did not change glucose and FFA concentration. Insulin increased PM GLUT4 and GLUT1 content 30 and 40?min after treatment and the increases were partially accompanied by decrease in transporter LDM content. E2 increased PM content and decreased LDM content only of GLUT4 at 30?min. Insulin generally, and E2 at 20?min increased CD36 content in PM fraction. Both hormones decreased CD36 LDM content 20?min after administration. Effect of combined treatment mostly did not differ from single hormone treatment, but occasionally, particularly in distribution of GLUT4, combined treatment emphasized single hormone effect, suggesting that insulin and E2 act synergistically in regulation of energy substrate transporters in cardiac tissue.     

Association between body mass index and muscularity in healthy older Japanese women and men

Background

Body mass index (BMI), expressed as the ratio of body mass to height squared (kg/m²), involves not only fat but also lean mass. The present study aimed to clarify how BMI is associated with total muscle mass (TMM) in older Japanese women and men.

Findings

Using a B-mode ultrasound apparatus, muscle thickness was measured at nine sites (forearm, upper arm anterior and posterior, thigh anterior and posterior, lower leg anterior and posterior, abdomen, and subscapular) for 346 women (BMI 16.40 to 33.11 kg/m²) and 286 men (BMI 16.86 to 31.18 kg/m²) aged 60.0 to 79.5 yrs. TMM was estimated using the product of the sum of the muscle thicknesses at the nine sites with height as an independent variable. For both sexes, the estimated TMM relative to height squared was significantly correlated with BMI (r = 0.688, P<0.0001 for women; r = 0.696, P<0.0001 for men), but the percentage of the estimated TMM in body mass was not.

Conclusion

These results indicate that, for older Japanese women and men, BMI is a simple and convenient index for assessing total muscularity.     

Association between molecular markers and blast resistance in an advanced backcross population of rice

An advanced backcross population consisting of 80 BC₃F₃ lines derived from rice vars. Vandana/Moroberekan was analysed for blast resistance and genotyped with 50 candidate genes and 23 simple sequence repeat (SSR) markers. Six candidate defence response genes [thaumatin, three nucleotide-binding site-leucine-rich repeat sequences from maize and two resistance gene analogue (RGA) markers] and one SSR marker (RM21) were significantly associated with partial blast resistance in rice (P=0.01). These markers accounted for phenotypic variation ranging from 9.6% to 29.4% and contributed to 76% of the total variation of percentage diseased leaf area (DLA) observed under natural infection. Four candidate genes (oxalate oxidase, 14-3-3 protein and two RGA markers) and four SSR markers (RM21, RM168, RM215 and RM250) were significantly associated with resistance to a single pathogen isolate, PO6-6. Among these, two markers were for DLA, five for lesion number and one for lesion size. These markers accounted for 9.1–28.7% of the phenotypic variation. A moderate correlation (r=0.48, P<0.01) was found between the level of partial resistance measured in the greenhouse and that measured under natural conditions. Analysis of BC₃F₄ progeny using genotypes of BC₃F₃ confirmed the phenotypic contribution of these markers. Cluster analysis of DNA profiles showed that the BC₃ population was genetically similar (>85%) to the recurrent parent Vandana. Although no obvious relationship between DNA profiles and resistant phenotypes was observed, three lines (VM19, VM46 and VM76) in a cluster with high similarity to Vandana (89–96%) expressed a high level of partial blast resistance in the field. Analysis of disease progress in the field confirmed the performance of selected lines based on greenhouse and nursery analyses. The advanced backcross progeny with resistance phenotypes tagged by markers will be useful for accumulating blast resistance in upland rice.Communicated by G. Wenzel     

Role of fatty acid transport protein 4 in metabolic tissues: insights into obesity and fatty liver disease

Fatty acid (FA) metabolism is a series of processes that provide structural substances, signalling molecules and energy. Ample evidence has shown that FA uptake is mediated by plasma membrane transporters including FA transport proteins (FATPs), caveolin-1, fatty-acid translocase (FAT)/CD36, and fatty-acid binding proteins. Unlike other FA transporters, the functions of FATPs have been controversial because they contain both motifs of FA transport and fatty acyl-CoA synthetase (ACS). The widely distributed FATP4 is not a direct FA transporter but plays a predominant function as an ACS. FATP4 deficiency causes ichthyosis premature syndrome in mice and humans associated with suppression of polar lipids but an increase in neutral lipids including triglycerides (TGs). Such a shift has been extensively characterized in enterocyte-, hepatocyte-, and adipocyte-specific Fatp4-deficient mice. The mutants under obese and non-obese fatty livers induced by different diets persistently show an increase in blood non-esterified free fatty acids and glycerol indicating the lipolysis of TGs. This review also focuses on FATP4 role on regulatory networks and factors that modulate FATP4 expression in metabolic tissues including intestine, liver, muscle, and adipose tissues. Metabolic disorders especially regarding blood lipids by FATP4 deficiency in different cell types are herein discussed. Our results may be applicable to not only patients with FATP4 mutations but also represent a model of dysregulated lipid homeostasis, thus providing mechanistic insights into obesity and development of fatty liver disease.