scholarly journals Tandem mass tag-based proteomics analysis of type 2 diabetes mellitus with non-alcoholic fatty liver disease in mice treated with acupuncture

2022 ◽  
Author(s):  
Guan Wang ◽  
Mengyuan Li ◽  
Shuo Yu ◽  
Mengqi Guan ◽  
Shiqi Ma ◽  
...  

Objective: To explore the proteomics profiles of hepatocytes of mice treated with acupuncture for type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD). Methods: We used a Tandem mass tag (TMT)-based quantitative proteomics approach to identify proteins with potential molecular mechanisms associated with acupuncture interventions for T2DM with NAFLD. Results: Acupuncture effectively improved body weight, blood glucose, and insulin levels in T2DM with NAFLD mouse models and reversed steatosis within hepatocytes. Quantitative TMT- based proteomics analysis identified a total of 4710 quantifiable proteins and 1226 differentially expressed proteins (DEPs) in the model control group (MCG) compared to the normal control group (NCG). The Acupuncture Treatment Group (ATG) presented in 122 DEPs compared to the MCG group. We performed a bioinformatics analysis, which revealed that DEPs enriched in the KEGG pathway after acupuncture treatment were mainly involved in the PPAR signalling pathway, fatty acid biosynthesis, fatty acid metabolism, fatty acid elongation, fat digestion, and absorption. We used parallel reaction monitoring (PRM) technology to explore the association of aldehyde oxidase 1 (Aox1), acyl-coenzyme A thioesterase 2 (Acot2), perilipin-2 (Plin2), acetyl-CoA carboxylase 1 (Acc), NADP-dependent malic enzyme (Me1), fatty acid synthase (Fasn), ATP-citrate synthase (Acly), fatty acid binding protein (Fabp2) with lipid synthesis, fatty acid oxidation and hepatocyte steatosis. Conclusions: Our results show that acupuncture can regulate the protein expression of T2DM in the NAFLD mice model, and can effectively improve hepatocyte steatosis, and has potential benefits for the clinical treatment of this disease.

2016 ◽  
Vol 73 (10) ◽  
pp. 910-920 ◽  
Author(s):  
Gordana Petrovic ◽  
Goran Bjelakovic ◽  
Daniela Benedeto-Stojanov ◽  
Aleksandar Nagorni ◽  
Vesna Brzacki ◽  
...  

Introduction/ aim. Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease of a broad histological spectrum, characterized by the accumulation of triglycerides in more than 5% of hepatocytes in the absence of consuming alcohol in quantities harmful to the liver. The aim of our study was to determine the importance of anthropometric and laboratory parameters as well as metabolic syndrome (MS) for the diagnosis of NAFLD and to estimate their influence on the degree of liver steatosis as evaluated by ultrasound (US). Methods. The study included 86 participants, 55 of whom had fatty liver diagnosed by ultrasound and they comprised the study group. The control group consisted of 31 control subjects. During the course of hospitalization at the Clinic of Gastroenterology and Hepatology, Clinical Centre Nis, the patients had their anamnesis taken, and anthropometric measurements as well as biochemical blood analyses and abdominal ultrasound were performed. Results. The patients with NAFLD had statistically higher values of body mass index (BMI), waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), levels of alanin and aspartate aminotransferase (ALT, AST), gamma-glutamyl transpeptidase (GGT) (p<0.001), low-density lipoprotein cholesterole (LDL), total bilirubin (TBIL) (p<0.05), total cholesterol (p<0.01), triglycerides (TGL), urates, C-reactive protein (CRP), ferritin, fibrinogenes, fasting blood glucose (FBG), insulin and Homeostasis Model Assessment (HOMA-IR) (p<0.001), whereas the levels of high-density lipoprotein cholesterol (HDL) were higher in the control group (p<0.05). In the NAFLD group, there were statistically significantly more patients with hypertension (72.73% vs. 12.90%, p<0.001) and type 2 diabetes mellitus (DM) (47.27%). Metabolic syndrome was determined in 48 (87.27%) patients of the study group. An equal number of patients, 16 of them (29.09%), had 3, 4 and 5 components of MS. In the NAFLD group there were 17 overweight (30.91%) (BMI from 25 kg/m2 to 29.9 kg/m2) and 38 (69.09%) obese patients. (BMI ? 30.0 kg/m2). The largest number of patients in the obesity group, 22 (40.00%) of them, had the first degree obesity (BMI from 30 kg/m2 to 34.99 kg/m2). The largest number of the NAFLD group patients - 23 (41.82%), had an ultrasound finding of grade 3 fatty liver, 20 patients (36.36%) had grade 2 and 12 (21.82%) grade 1 fatty liver. Kruskal-Wallis test and ANOVA analysis showed statistically significant differences between groups with different US grade for insulin, LDL-cholesterol, WC, BMI (p<0.05), as well as HOMA-IR and body weight (BW) (p<0.01). Metabolic syndrome was statistically more present in patients with US finding grades 2 and 3 (p<0.01) in relation to grade 1 US finding, as well as obesity, hypertension and DM type 2 (p<0.05). Conclusion. The results of our study have confirmed that a high percentage of patients with high risk factors (DM, MS, dyslipidemia, hypertension) have NAFLD.


2008 ◽  
Vol 78 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Suano de Souza ◽  
Silverio Amancio ◽  
Saccardo Sarni ◽  
Sacchi Pitta ◽  
Fernandes ◽  
...  

Objectives: To evaluate the frequency of non-alcoholic fatty liver disease, the retinol serum levels, lipid profile, and insulin resistance in overweight/obese children. To relate these biochemical variables with the risk of this disease in the population studied. Methods: The study was cross-sectional and prospective, with 46 overweight/obese school children (28 female, 18 male; mean age 8.6 years). The control group consisted of 45 children, paired by age and gender. Hepatic steatosis, evaluated by ultrasound, was classified as normal, mild, moderate, or severe. Also evaluated were serum retinol levels; thiobarbituric acid reactive substances; lipid profile; and fasting glucose and serum insulin levels, used for the calculation of the Homeostasis Model Assessment. Results: Hepatic ultrasound alterations were found in 56.5% and 48,9% of the overweight/obese and control group children, respectively. Presence of obesity was associated with high levels of triglycerides (OR = 4.6; P = 0.002). In the studied children, the risk of steatosis was related to a trend to a higher percentage of retinol inadequacy (OR = 2.8; p = 0.051); there was no association with thiobarbituric acid reactive substances, lipid profile, or insulin resistance. Conclusions: The high frequency of non-alcoholic fatty liver disease in both groups, evaluated by hepatic ultrasound, in low-socioeconomic level children, independent of nutritional condition and without significant association with insulin resistance, emphasizes that especially in developing countries, other risk factors such as micronutrient deficiencies (e.g. vitamin A) are involved.


2016 ◽  
Vol 25 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Andrea Fialho ◽  
Andre Fialho ◽  
Prashanthi Thota ◽  
Arthur J. McCullough ◽  
Bo Shen

Background: Changes in gut bacteria play a role in type 2 diabetes mellitus (DM) and hepatic steatosis. There is a lack of studies evaluating the frequency and risk factors for non-alcoholic fatty liver disease (NAFLD) in patients tested for small intestinal bacterial overgrowth (SIBO). Aim: To evaluate the frequency of NAFLD and associated risk factors in patients tested for SIBO. Methods: In this case-control study, 372 eligible patients submitted to glucose hydrogen/methane breath test for SIBO who also had an abdominal imaging study were included. Patients were divided into SIBO-positive and SIBO-negative groups. Clinical, demographic and laboratory variables were evaluated in addition to the presence of NAFLD on abdominal imaging. Results: Of the 372 eligible patients, 141 (37.9%) were tested positive for SIBO (study group) and 231 (62.1%) were negative for it (control group). NAFLD occurred in 45.4% (64/141) of the study group compared to 17.3% (40/231) of the control group (p<0.001). Patients in the study group were found to have higher rates of elevated aspartate aminotransferase (AST) (20.6% vs. 11.3%; p=0.034) and alanine aminotransferase (ALT) levels (56.0% vs. 40.7%; p= 0.039), type 2 diabetes (23.4% vs. 13.9%; p=0.041), hypertension (54.6% vs. 40.3%; p=0.046) and metabolic syndrome (78.0% vs. 60.2%; p=0.020). In the multivariate analysis, SIBO (odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.14-3.31; p=0.014), type 2 DM (OR: 3.04; 95%CI: 1.57-5.90; p=0.001) and obesity (OR: 3.58; 95%CI: 1.70-7.54; p=0.001) remained associated with NAFLD.Conclusion: Patients with SIBO have an increased risk for hepatic steatosis and may benefit from aggressive control of the risk factors for NAFLD including metabolic syndrome. Abbreviations: ALT: alanine aminotransferase; AST: aspartate aminotransferase; BMI: body mass index; CTE: computed tomography enterography; DM: diabetes mellitus; ETOH: ethanol; IL: interleukin; LPS: lipopolysaccharide; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PPI: proton pump inhibitor; SIBO: small intestinal bacterial overgrowth; TLR-4: toll-like receptor 4; TMAO: trimethylamine-N-oxide (TMAO); TNF-α: tumor necrosis factor alpha.


2019 ◽  
Vol 17 (1) ◽  
pp. 1328-1338
Author(s):  
Yufeng Xing ◽  
Chuantao Zhang ◽  
Fenfen Zhai ◽  
Tianran Zhou ◽  
Xiang Cui ◽  
...  

AbstractCells with non-alcoholic fatty liver disease (NAFLD) were studied to determine the mechanism of liver deficiency via the AdipoR2-PPARa pathway. NAFLD cells were randomly divided into a normal control group, blank control group, model group, low dose group, medium dose group, and high dose group. The NAFLD models were established by incubating the cells with linoleic acid (LA) and palmitic acid (PA) (2:1) for 24 h. The test groups were incubated with different doses of Shugan Xiaozhi Fang extract. The pathological changes in cells that accumulated lipids were detected by Oil Red O staining. Malondialdehyde (MDA) and triglyceride (TG) levels were measured. The apoptosis of cells was evaluated by flow cytometry. The levels of AdipoR2, PPARa, CD36, acyl-CoA mRNA, and protein were confirmed by RT- PCR and Western blot. The results of the Oil Red O staining demonstrated that the NAFLD cell model was successfully established. Compared with the model group, the levels of TG and MDA in the groups that received low, medium, and high doses of Shugan Xiaozhi were significantly lower (P<0.01), and a dose effect was evident. In addition, the expression of AdipoR2, PPARa, CD36, acyl-CoA protein, and mRNA in the Shugan Xiaozhi-treated groups was upregulated. Furthermore, the levels of AdipoR2, PPAR, CD36, acyl-CoA protein, and mRNA in all drug treatment groups that were extracted from L-O2 normal human hepatocytes were significantly upregulated (P<0.01). Moreover, the factor pattern of HepG2 human liver carcinoma cells was similar to that of L-O2. The levels of AdipoR, CD36, acyl-CoA, and AdipoR mRNA in the HepG2 low group were increased (P<0.05). AdipoR, PPAR, CD36, and acyl-CoA protein levels and AdipoR mRNA expression were significantly increased in the intermediate dose group and high dose group (P<0.01). Shugan Xiaozhi Fang attenuates hepatic lipid deposition in NAFLD induced by incubating with LA and PA for 24 h, which is associated with the activation of the AdipoR2-PPARα pathway.


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