Abnormal metabolism of nonesterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), an LD‐binding protein, regulates the storage and hydrolysis of TG in LD. However, its roles and underlying mechanisms in the liver remain unknown. Here we found that Plin5 expression was increased in steatotic livers. Using Plin5 knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller‐sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. Plin5‐deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression and activity of PPARα stimulated by the increased NEFA levels. Meanwhile, Plin5‐deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically, we found that Plin5 blocks adipose triglyceride lipase (ATGL)‐mediated lipolysis by competitively binding to comparative gene identification‐58 (CGI‐58) and disrupting the interaction between CGI‐58 and ATGL. Conclusion: Plin5 is an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis. This provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity. (Hepatology 2015;61:870–882)
Background and Purpose
The gut microbial metabolite butyrate is linked to the modulation of metabolic disease. The mechanism by which butyrate effects in atherosclerosis is unknown. Hence, the present investigation into effects of butyrate on high‐fat diet‐fed ApoE−/− mice after 16 weeks' administration.
Experimental Approach
Gut microbiota composition was analysed via 16S rRNA gene sequencing of caecal contents. The effects of butyrate on atherosclerosis were evaluated in vivo using the ApoE−/− mice model. Serum lipids and glucose were analysed for physiological changes and differentially expressed genes in liver samples were identified by hepatic transcriptome profiling. The proteins involved in reverse cholesterol transport were quantified by Western blot and immunohistochemical staining. Finally, the up‐regulatory effects of butyrate on ATP‐binding cassette sub‐family A member 1 (ABCA1) were further evaluated in RAW 264.7 cells along with role of specificity protein 1 by inhibition and silencing.
Key Results
Oral gavage of butyrate altered microbiota composition and enhanced gut microbial diversity that was decreased by high fat diet (HFD). Butyrate treatment significantly inhibited the HFD‐induced atherosclerosis as well as hepatic steatosis without changing body weight gain in ApoE−/− mice. Butyrate had metabolic effects on the liver by regulation of gene expression involved in lipid/glucose metabolism. Furthermore, ABCA1 was significantly induced by butyrate in vivo, ex vivo and in vitro and Sp1 pathway was identified as a potential mechanism.
Conclusion and Implications
Butyrate ameliorates HFD‐induced atherosclerosis in ApoE−/− mice via ABCA1‐mediated cholesterol efflux in macrophages, which suggesting a promising therapeutic strategy for protecting against atherosclerosis.
Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.
CHCs and hospitals face different challenges regarding patient satisfaction. Further healthcare reform in China need to adopt more measures (e.g. increasing quality of primary care, setting up a referral medical system etc.) to improve patient satisfaction.
Aims and objectives: The present study was aimed at describing the status of job burnout and exploring the mediating roles of psychological capital and professional identity on the association between organisational justice and job burnout.Background: With the shortage of nurses all over the world, nurses' job burnout has become the focus of studies in recent years. However, limited published research has examined the mediating roles of psychological capital and professional identity on the association between organisational justice and job burnout within hospital contexts in China.
Design: A cross-sectional design.Methods: A total of 1,009 nurses were enrolled from a major general hospital located in Qiqihar City in the northeast of China from March-July 2018, and asked to complete questionnaires regarding organisational justice, psychological capital, professional identity and job burnout. The STROBE checklist was adhered to in this study.
Results:It was observed that the overall proportion of nurses with job burnout was 58.8%. All the correlations among organisational justice, psychological capital, professional identity and job burnout were statistically significant, with coefficients ranging between −0.487-0.863. Psychological capital and professional identity had indirect effects equal to −0.072 and −0.142, respectively, on the association between organisational justice and job burnout, taking up 13.7% and 26.9% of the total effect, respectively. The serial indirect effect of psychological capital and professional identity was −0.129, accounting for 24.5% of the total effect.
Conclusions:This study showed the necessity of addressing the status of job burnout among Chinese nurses. Psychological capital and professional identity may | 2913 REN Et al.
ObjectivesWe evaluated the association between BMI and body weight perception in a sample of children and adolescents.MethodsA cross-sectional school-based study was conducted among 7–18 year-olds (N = 9727) from 4 districts in Jilin City, China. We calculated BMI from measured weight and height and assessed body weight perception using a single questionnaire item. We analyzed these data using SPSS version 20.0.ResultsApproximately 19.8% of these youth perceived themselves as underweight, 57.8% as normal weight, and 22.4% as overweight. In reality, 4.9% were underweight, 64.3% were normal weight, and 30.8% were overweight. Furthermore, approximately 66.4% of these Chinese youth correctly perceived their body image, 28.2% underestimated their true body image, and 5.4% overestimated their weight status. Girls were more likely than boys to overestimate their weight (χ2 = 135.4, p < 0.05). Adolescents 13–18 years old were more likely than children 7–12 years old to overestimate their weight (χ2 = 248.4, p < 0.05). Senior high school students were the most likely to overestimate their weight (χ2 = 297.6, p < 0.05). Kappa tests revealed significant differences in consistency analysis of BMI and body weight perception (Kappa = 0.352, p < 0.05). Kappa < 0.4, the consistency of BMI and body weight perception was poor.ConclusionsA mismatch existed between BMI and body weight perception among these children and adolescents. Thus, schools and parents should take steps to help them improve weight management and overall health awareness.
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