Combined serum CTRP7 and CTRP15 levels as a novel biomarker for insulin resistance and type 2 diabetes mellitus.

Aims: This study aimed to examine the alterations in the serum CTRP7 and CTRP15 concentrations in patients newly diagnosed with type 2 diabetes mellitus (T2DM) and to assess the diagnostic potential of the log10 (CTRP7+CTRP15) for insulin resistance (IR) and T2DM. Methods: Serum CTRP7, CTRP15, and adiponectin levels were measured using an enzyme-linked immunosorbent assay (ELISA). Bioinformatics analysis was conducted to investigate CTRP7 and CTRP15-related genes and metabolic signaling pathways. Results: Log10 (CTRP7+CTRP15) levels were notably elevated in the impaired glucose tolerance (IGT) and T2DM cohorts compared with those in the normal control (NGT) cohort. Log10(CTRP7+CTRP15) exhibited positive correlations with HOMA-IR, area under the glucose curve (AUCg), HbA1c%, triglyceride (TG), visceral adiposity index (VAI), body mass index (BMI), and free fatty acid (FFA), levels but negative correlations with adiponectin. Multivariate stepwise regression analysis revealed that HOMA-IR, BMI, HbA1c and FFA levels were independent factors affecting the log10 (CTRP7+CTRP15). Logistic regression analysis revealed that log10 (CTRP7+CTRP15) was independently associated with T2DM and significantly associated with increased risk. Receiver operating characteristic (ROC) curve analysis indicated that the predictive value of log10 (CTRP7+CTRP15) for T2DM and IR was superior to that of CTRP7 or CTRP15 alone. Intervention studies demonstrated that insulin, FFAs and acute exercise contribute to the elevation of serum CTRP7 levels, while hyperglycemia inhibited CTRP7 secretion. Short-term changes in blood glucose, insulin, FFA and acute exercise had minimal effects on serum CTRP15 levels. Bioinformatics analysis revealed that CTRP7 and CTRP15 interact with multiple metabolism-related genes and are enriched in glucose and lipid metabolism-related pathways. Conclusion: Log10 (CTRP7+CTRP15) may serve as a valuable diagnostic marker for the management of metabolic-related diseases, particularly T2DM and IR.

NOD1 deficiency ameliorates the progression of diabetic retinopathy by modulating bone marrow-retina crosstalk.

BACKGROUND: Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) plays a pivotal role in inducing metabolic inflammation in diabetes. Additionally, the NOD1 ligand disrupts the equilibrium of bone marrow-derived hematopoietic stem/progenitor cells, a process that has immense significance in the development of diabetic retinopathy (DR). We hypothesized that NOD1 depletion impedes the advancement of DR by resolving bone marrow dysfunction. METHODS: We generated NOD1-/--Akita double-mutant mice and chimeric mice with hematopoietic-specific NOD1 depletion to study the role of NOD1 in the bone marrow-retina axis. RESULTS: Elevated circulating NOD1 activators were observed in Akita mice after 6 months of diabetes. NOD1 depletion partially restored diabetes-induced structural changes and retinal electrical responses in NOD1-/--Akita mice. Loss of NOD1 significantly ameliorated the progression of diabetic retinal vascular degeneration, as determined by acellular capillary quantification. The preventive effect of NOD1 depletion on DR is linked to bone marrow phenotype alterations, including a restored HSC pool and a shift in hematopoiesis toward myelopoiesis. We also generated chimeric mice with hematopoietic-specific NOD1 ablation, and the results further indicated that NOD1 had a protective effect against DR. Mechanistically, loss of hematopoietic NOD1 resulted in reduced bone marrow-derived macrophage infiltration and decreased CXCL1 and CXCL2 secretion within the retina, subsequently leading to diminished neutrophil chemoattraction and NETosis. CONCLUSIONS: The results of our study unveil, for the first time, the critical role of NOD1 as a trigger for a hematopoietic imbalance toward myelopoiesis and local retinal inflammation, culminating in DR progression. Targeting NOD1 in bone marrow may be a potential strategy for the prevention and treatment of DR.

Empagliflozin improves kidney senescence induced by D-galactose by reducing sirt1-mediated oxidative stress.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have received widespread attention because of their significant protective effects on the kidney. Previous studies have shown that Sirt1, as which is an antiaging protein, is closely related to the maintenance of redox homeostasis. The goal of this study was to determine whether empagliflozin could ameliorate D-galactose-induced renal senescence in mice, and examine the possible mechanisms of Sirt1. We constructed a rapid ageing model in mice by administering D-galactose. An ageing model was constructed by treating cells with high glucose. Treadmill and Y-maze tests were used to assess exercise tolerance and learning memory ability. Pathologically stained sections were used to assess kidney injury. Tissue and cell senescence were evaluated by senescence-associated ß-galactosidase staining. The expression levels of P16, SOD1, SOD2 and Sirt1 were detected by immunoblotting. D-gal-treated mice exhibited significant age-related changes, as measured by behavioural tests and ageing marker protein levels. empagliflozin alleviated these ageing manifestations. In addition, Sirt1, SOD1 and SOD2 levels were downregulated in model mice and upregulated by empagliflozin treatment. Empagliflozin had similar protective effects at the cellular level, and these effects were reduced by the Sirt1 inhibitor. Empagliflozin has an antiaging effect, which may be related to reducing Sirt1-mediated oxidative stress.

Peptidoglycan-Mediated Bone Marrow Autonomic Neuropathy Impairs Hematopoietic Stem/Progenitor Cells via a NOD1-Dependent Pathway in db/db Mice.

Impairment of bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) contributes to the progression of vascular complications in subjects with diabetes. Very small amounts of bacterial-derived pathogen-associated molecular patterns (PAMPs) establish the bone marrow cell pool. We hypothesize that alteration of the PAMP peptidoglycan (PGN) exacerbates HSPC dysfunction in diabetes. We observed increased PGN infiltration in the bone marrow of diabetic mice. Exogenous administration of PGN selectively reduced the number of long-term repopulating hematopoietic stem cells (LT-HSCs), accompanied by impaired vasoreparative functions in db/db mouse bone marrow. We further revealed that bone marrow denervation contributed to PGN-associated HSPC dysfunction. Inhibition of NOD1 ameliorated PGN-induced bone marrow autonomic neuropathy, which significantly rejuvenated the HSPC pools and functions in vivo. These data reveal for the first time that PGN, as a critical factor on the gut-bone marrow axis, promotes bone marrow denervation and HSPC modulation in the context of diabetes.

Virtual Learning During the COVID-19 Pandemic: A Bibliometric Review and Future Research Agenda.

Virtual learning has emerged as a powerful platform for students and academicians in the "new normal" owing to the availability of advanced technological tools and platforms. Recently, considerable literature has grown up around the role of digital and remote technologies in learning and teaching during the ongoing COVID-19 pandemic. However, the research evidence on this topic is still fragmented, requiring a synthesis of this rapidly growing literature. This study aims to assess the key research trends in virtual learning during the COVID-19 pandemic through a bibliometric analysis of 1595 studies from 589 journals during 2020-21. Our study highlights the influential aspects, such as the most contributing countries, journals, authors, and keywords in this research field. We identified the following four main research trends: 1) challenges in online learning and blended learning strategies; 2) student-centered, collaborative learning, and curriculum design; 3) home-based laboratory learning; and 4) teachers' professional competence and interdisciplinary learning. We conclude this research by discussing the implications for regulators and educational institutions, and directions for future research.

Exploring the Motivational Factors for International Students to Study in Chinese Higher Education Institutions.

China has witnessed a remarkable surge in the enrollment of international students in recent years and the state government has made a massive investment to build key universities of international repute. These trends made it imperative to investigate the underlying motivational aspirations of foreign students arriving from diverse regions to get enrolled in public sector Chinese universities. The present study designed an in-depth survey questionnaire and collected data from 618 foreign students enrolled in postgraduate programs at seven key state universities in the Hubei province of China. The item-based, dimension-based, and variable-level analysis approach is used to systematically uncover the facets of the internationalization of Chinese higher education in the current setting. In so doing, we employ descriptive statistics, principal component analysis, ANOVA, correlation and regression estimations, and path models to ensure the robustness of empirical outcomes. In light of the push and pull factor model regarding motivational factors for foreign students to study in China, the findings of this study assert that academic pursuits mainly dictate the international student's decision to attain higher education in China. While obtaining a foreign degree, international image prestige, and better employment prospects after the completion of the degree were the key intentions that mainly shape the students' decision to get enrolled in Chinese universities. Furthermore, the discriminant analysis posits that international students significantly differ in their motivational dimensions to obtain a higher degree from China. As foreign students from Asia and Africa mainly have academic goals while Europeans and Americans predominantly have pleasure and enjoyment motives to study in China. The outcomes of this research can assist Chinese administrators to understand the key motivational factors for foreign students to study in China and devise a policy accordingly to attract high quality foreign talent.

Increased plasma osteopontin levels are associated with nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus.

Nonalcoholic fatty liver disease (NAFLD) commonly occurs in patients with type 2 diabetes mellitus (T2DM). Osteopontin (OPN) is a multifunctional protein with pleiotropic physiological functions. This study aimed to investigate the interrelation between circulating OPN and NAFLD in T2DM patients. Overall, 249 subjects were classified into 4 groups: 53 patients with NAFLD and T2DM; 57 with newly diagnosed T2DM; 59 with NAFLD; and 80 healthy age- and sex-matched controls. Serum OPN was measured by ELISA. The OPN distribution in the pooled data was divided into quartiles; significant trends across increasing quartiles were estimated by the Cochran-Armitage trend test. Compared with the controls, circulating OPN concentrations were significantly elevated in NAFLD patients and T2DM patients with or without NAFLD. Serum OPN levels were higher in the overweight/obese group than that in the lean group. Circulating OPN levels were positively correlated with CRP, age, BMI, SBP, DBP, HbA1c, UA, TGs, WBCs, neutrophils, FBG, and HOMA-IR and negatively correlated with ADP, albumin and HDL. Age, albumin, HbA1c, HDL and hsCRP were independently related to circulating OPN. The relative risks for NAFLD, T2DM and T2DM with NAFLD increased significantly along with increasing OPN quartiles based on the Cochran-Armitage trend test. OPN is an optimal predictor in the diagnosis of T2DM with NAFLD and T2DM and may contribute to the aggravation of the metabolic state.

DOCK5 regulates energy balance and hepatic insulin sensitivity by targeting mTORC1 signaling.

The dedicator of cytokinesis 5 (DOCK5) is associated with obesity. However, the mechanism by which DOCK5 contributes to obesity remains completely unknown. Here, we show that hepatic DOCK5 expression significantly decreases at a state of insulin resistance (IR). Deletion of DOCK5 in mice reduces energy expenditure, promotes obesity, augments IR, dysregulates glucose metabolism, and activates the mTOR (Raptor)/S6K1 pathway under a high-fat diet (HFD). The overexpression of DOCK5 in hepatocytes inhibits gluconeogenic gene expression and increases the level of insulin receptor (InsR) and Akt phosphorylation. DOCK5 overexpression also inhibits mTOR/S6K1 phosphorylation and decreases the level of raptor protein expression. The opposite effects were observed in DOCK5-deficient hepatocytes. Importantly, in liver-specific Raptor knockout mice and associated hepatocytes, the effects of an adeno-associated virus (AAV8)- or adenovirus-mediated DOCK5 knockdown on glucose metabolism and insulin signaling are largely eliminated. Additionally, DOCK5-Raptor interaction is indispensable for the DOCK5-mediated regulation of hepatic glucose production (HGP). Therefore, DOCK5 acts as a regulator of Raptor to control hepatic insulin activity and glucose homeostasis.

Predicting significance of COX-2 expression of peripheral blood monocyte in patients with coronary artery disease.

BACKGROUND: Cyclooxygenase-2 (COX-2) plays an important role in the monocyte-platelet aggregate (MPA)-medicated inflammatory response and possible coronary artery disease (CAD). This study aimed to assess the predicting significance of COX-2 expression in peripheral blood monocyte for CAD. METHODS: A total of 66 patients with CAD including stable angina (SA) and unstable angina (UA) were enrolled. The inflammatory indexes including white blood cell (WBC) count, high-sensitive C reactive protein (hs-CRP), serum monocyte chemoattractant protein-1 (MCP-1) and MPA levels were measured. The western-blotting assay and reverse transcription-polymerase chain reaction (RT-PCR) analysis were used to detect the COX-2 expression in peripheral blood monocytes. Furthermore, the correlation between COX-2 expression and MPA levels, and the association of COX-2 expression with CAD risk were assessed. RESULTS: The UA patients demonstrated higher levels of inflammatory indexes than the SA patients (P<0.001). Simultaneously, higher MPA levels and enhanced COX-2 expression were observed in the UA patients (P<0.01). The patients with enhanced COX-2 expression exhibited higher MPA than those without (P<0.01), and patients with increased MPA also demonstrated enhanced COX-2 expression (P<0.001). Moreover, the levels of COX-2 protein expression was positively related to the MPA formation rates (R2=0.4933, P<0.01), and enhanced COX-2 expression was independently associated with CAD risk [odds ratio (OR): 6.322, 95% confidence interval (CI): 4.544-8.978 ]. CONCLUSIONS: The COX-2 expression of peripheral blood monocytes can be used as an independent predictor for CAD.

The characteristics of 24-hour ambulatory blood pressure monitoring and its relationship with cardiovascular target organ damage in Chinese Han patients with concomitant type 2 diabetes and hypertension.

OBJECTIVE: The objective of this study was to investigate the characteristics of 24-hour ambulatory blood pressure monitoring and its relationship with cardiovascular target organ damage (left ventricular hypertrophy and carotid atherosclerosis) in Chinese Han patients with concomitant type 2 diabetes mellitus and hypertension. METHODS: A total of 830 hypertensive patients with or without type 2 diabetes mellitus were divided into four groups according to blood pressure patterns. Clinical characteristics and 24-hour ambulatory blood pressure monitoring indexes were compared among the four groups. Multivariable logistic regression was used to identify the associations among clinical characteristics, blood pressure variability and cardiovascular target organ damage. RESULTS: The prevalence of the non-dipper blood pressure profile (51.32% vs. 24.33%) was higher in patients with type 2 diabetes mellitus and hypertension than in those without type 2 diabetes mellitus. Logistic regression analysis showed that glycosylated haemoglobin A1c, 24hSBP, 24hSSD, dSBP, nSBP and nSSD were independently associated with the non-dipper blood pressure pattern. Type 2 diabetes mellitus patients with the non-dipper blood pressure pattern showed a higher occurrence of target organ damage compared to patients in the other three groups. Multivariate regression analyses revealed that duration of hypertension, fasting blood glucose, dDBP and nDSD were associated with left ventricular hypertrophy. Age, haemoglobin A1c, LDL-C, nSBP and HDL-C were independently related to carotid atherosclerosis. CONCLUSION: In the Chinese Han population, patients with concomitant type 2 diabetes mellitus and hypertension showed a remarkably high prevalence of non-dipper blood pressure patterns. Abnormal systolic blood pressure level and hyperglycemia were significantly associated with a non-dipper blood pressure pattern. Non-dipper blood pressure pattern, hyperglycemia and dyslipidemia were closely related to left ventricular hypertrophy and carotid atherosclerosis.

Efficacy of low-level light therapy for treatment of diabetic foot ulcer: A systematic review and meta-analysis of randomized controlled trials.

AIMS: The goal of this systematic review and meta-analysis based on seven Randomized control trials (RCTs) is to examine whether Low-level light therapy (LLLT) is effective at healing diabetic foot ulcer (DFU) and to provide evidence-based recommendations and clinical guidelines for the future clinical treatment of DFUs. METHODS: Medline, Embase, Scopus, Cochrane Library, and Web of Science databases were searched for studies published up to June 30, 2017, without language or data restrictions. RCTs that investigated the use of LLLT for DFU treatment were included. Standard methods of meta-analysis were performed to evaluate outcomes of LLLT on the healing of DFU. RESULTS: Seven RCTs involving 194 participants were eligible for this systematic review and meta-analysis. The results of meta-analysis showed that LLLT has emerged as a potential noninvasive treatment for DFUs, as LLLT was found to effectively reduce the ulcer area [weighted mean difference (WMD) 34.18, 95% confidence intervals (CI) 19.38-48.99, P < 0.00001], improve the complete healing rate [odds ratio (OR) 6.72, 95% CI 1.99-22.64, P = 0.002]. Qualitative analysis of the included RCTs found that LLLT also played a role in the treatment of DFUs through promoting rapid granulation formation and shortening ulcer closure time, as well as alleviating foot ulcer pain. None of the treatment-related adverse event was reported. CONCLUSIONS: LLLT was recognized as a potential method in the comprehensive treatment of DFUs. Further well designed and high-quality studies are required to confirm the role of LLLT in the management of DFUs.

Effect of metformin treatment during pregnancy on women with PCOS: a systematic review and meta-analysis.

PURPOSE: Some previous studies have found that continued metformin use is beneficial in the management of polycystic ovary syndrome (PCOS) in pregnant women. A systemic review and meta-analysis were needed to more fully assess the effects of metformin on pregnant PCOS patients. METHODS: The literature was fully searched using MEDLINE, EMBASE, SCOPUS, and COCHRANE for continued metformin use during pregnancy in women with PCOS. A systematic review and meta-analysis were performed to evaluate the comprehensive effects of continued metformin treatment on pregnancy-related outcomes in these women. RESULTS: Eleven eligible studies out of 127 relevant publications were included in meta-analysis. The rates of early pregnancy loss and preterm delivery were found to be significantly decreased in metformin-treated PCOS women. A non-significant difference was found in fetal abnormality and fetal birth weight between the metformin-treated and the non-treated groups. The incidence of gestational diabetes mellitus (GDM) and hypertension/preeclampsia were not significantly different in the two groups, probably because of inconsistent results in the subgroup analysis. CONCLUSIONS: Our results showed that continued use during of metformin, during pregnancy in women with PCOS, had no effect on incidence of fetal abnormalities or fetal birth weight. The effects of metformin on GDM and hypertension/preeclampsia should be determined through high-quality randomized controlled trials.

NAMPT knockdown attenuates atherosclerosis and promotes reverse cholesterol transport in ApoE KO mice with high-fat-induced insulin resistance.

NAMPT has been suggested association with atherosclerosis and insulin resistance. However, the impact of NAMPT on atherosclerosis remained unknown. Therefore, the objective of this study was to use a NAMPT loss-of-function approach to investigate the effect of NAMPT on atherosclerosis in hypercholesterolemic mice. We demonstrated that a specific NAMPT knockdown increased plasma HDL-C levels, reduced the plaque area of the total aorta en face and the cross-sectional aortic sinus, decreased macrophage number and apoptosis, and promoted RCT in HFD-fed ApoE KO mice. These changes were accompanied by increased PPARα, LXRα, ABCA1 and ABCG1 expressions in the liver. NAMPT knockdown also facilitated cholesterol efflux in RAW264.7 cells. We further investigated the effect of NAMPT knockdown on the PPARα-LXRα pathway of cholesterol metabolism with MK886 (a selective inhibitor of PPARα) in RAW264.7 macrophages. MK886 abolished the ability of NAMPT knockdown to decrease intracellular cholesterol levels to enhance the rate of (3)H-cholesterol efflux and to increase ABCA1/G1 and LXRα expressions in RAW264.7 macrophages. Our observations demonstrate that NAMPT knockdown exerted antiatherogenic effects by promoting cholesterol efflux and macrophage RCT through the PPARα- LXRα- ABCA1/G1pathway in vitro and in vivo.

Trends in the Levels of Serum Lipids and Lipoproteins and the Prevalence of Dyslipidemia in Adults with Newly Diagnosed Type 2 Diabetes in the Southwest Chinese Han Population during 2003-2012.

Objective. To determine the trends of serum lipid levels and dyslipidemia in adults newly diagnosed with type 2 diabetes mellitus during 2003-2012 in Southwest China. Methods. Serum lipid measurements of 994 adults were obtained from 5 independent, cross-sectional studies (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012). The main outcome measures were mean serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels; body mass index; hemoglobin A1C level; and the percentages of patients with dyslipidemia, hypertension, coronary heart disease, and cerebrovascular disease. Results. The mean total cholesterol and low-density lipoprotein cholesterol levels increased from 4.92 ± 1.15 to 5.30 ± 1.17 mmol/L (P = 0.039) and 2.72 ± 0.83 to 3.11 ± 1.09 mmol/L (P = 0.004), respectively, and the mean HDL cholesterol level declined from 1.22 ± 0.30 to 1.06 ± 0.24 mmol/L (P < 0.001). The percentages of patients with dyslipidemia increased gradually. The incidence of coronary heart and cerebrovascular diseases increased from 8.2% to 19.1% and 6.6% to 15.3%, respectively (P < 0.05). Conclusion. Unfavorable upward trends were observed in serum lipid levels and the prevalence of dyslipidemia, coronary heart disease, and cerebrovascular disease in adults newly diagnosed with type 2 diabetes mellitus in Southwest China during 2003-2012.

Elevated circulating levels of irisin and the effect of metformin treatment in women with polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is an insulin resistance (IR) state, like obesity and type 2 diabetes mellitus (T2DM). Although previous studies have suggested a correlation between irisin and the metabolic parameters associated with obesity and T2DM, the results have been inconsistent. OBJECTIVE: Our objective was to (1) determine circulating irisin levels in women with PCOS and control subjects, (2) examine the relationship of irisin and conventional markers of insulin resistance, and (3) examine irisin changes with interventions modulating IR in PCOS women. PATIENTS AND DESIGN: This study was comprised of a series of cross-sectional and interventional studies of 178 PCOS and 123 healthy women from the general population and outpatients of the Internal Medicine Department at the Second Affiliated Hospital, Chongqing Medical University, China. Forty seven women with PCOS were randomly assigned to 6 months of oral metformin (850 mg bid). The oral glucose tolerance test (OGTT) and the euglycemic-hyperinsulinemic clamp (EHC) were performed to assess glucose tolerance and insulin sensitivity. Outcome measures were IR (AUC(Insulin) and M values) on an OGTT and EHC, irisin levels, and metabolic markers. RESULTS: Circulating irisin was significantly higher in both overweight/obese (body mass index [BMI] ≥ 25 kg/m(2)) and PCOS women (P < .01). Circulating irisin levels correlated with BMI, WHR, FAT%, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), AUC(Insulin), homeostasis model assessment of insulin resistance (HOMA2-IR), M values, and free androgen index (FAI). During EHC, short-term hyperinsulinemia exhibited an inhibitory effect on irisin levels. After 6 months of metformin treatment, there was a significant decrease in circulating irisin in PCOS women following improved IR. CONCLUSIONS: These data suggest that irisin may be a useful marker of IR in PCOS women.

Association of ApoE gene with type 2 diabetic nephropathy in a Chinese population: a meta-analysis of case-control studies.

Studies based on Chinese populations reported that inconsistent results were found on the association of ApoE gene polymorphisms with type 2 diabetic nephropathy (T2DN). Therefore, we performed this meta-analysis to provide a reliable evaluation of the associations between ApoE gene polymorphisms and T2DN. MEDLINE, EMBASE, Chinese Wanfang database and Chinese VIP database were searched for studies that reported the associations of ApoE gene polymorphisms with type 2 diabetic nephropathy in a Chinese population up to Dec 2013. A meta-analysis was performed to assess heterogeneity and combine results by using software RevMan 4.3.1. Sensitivity analysis and publication bias were conducted. Data from 16 published studies involving 4320 individuals were eligible for inclusion. After heterogeneity test in each analysis, corresponding effect models were applied to quantitatively syntheses data. The ApoE allele e2 and genotype e2/e3 occurred more frequently in T2DN than in T2DNN and NC group. Their ORs and 95%CIs in T2DN were 1.75 (1.27-2.42) and 1.68 (1.20-2.38) when compared with T2DNN, respectively (P<0.05); 2.59 (1.74-3.85) and 2.43 (1.61-3.65) when compared with NC, respectively (P<0.05). The publication bias diagnostics test and sensitivity analysis confirmed the reliability and stability of this meta-analysis. These findings support the significant association between ApoE gene polymorphisms and T2DN. It was revealed that allele e2 and genotype e2/e3 were risk factors for T2DN and allele e3 and genotype e3/e3 played a protective role in T2DN. Further studies will be needed to confirm the conclusion.

[Liraglutide protects against nonalcoholic fatty liver disease in ApoE knockout mice with high-fat diet and silenced Acrp30 by increasing AMPK].

OBJECTIVE: To investigate the mechanism of liraglutide-mediated protection against nonalcoholic fatty liver disease (NAFLD) using aApoE knockout (KO) mouse with high-fat diet (HFD) and Acrp30 knockdown. METHODS: Fifty-six male ApoE KO mice were divided into the following six modeling and experimental groups:regular chow fed (ApoE KO, n=10), HFD fed (HF, n=10), HFD+Adenovirus (Ad)-small hairpin (sh) Acrp30 (Ad-shAcrp30, n=10), HFD+Ad-shGreen Fluorescent Protein (GFP) (Ad-shGFP, n=6), HFD+Ad-shAcrp30+liraglutide (liraglutide, n=10), and HFD+Ad-shAcrp30+saline (saline, n=10). Weight-matched C57BL/6 mice on the regular chow diet were used as the control group (WT control, n=10).All mice were fed their assigned diet for 16 weeks.The Ad-shGFP or Ad-shAcrp30 was injected by tail vein at the end of 14 and 15 weeks.Mice in the liraglutide group received 1 mg/kg of the drug, twice daily, intraperitoneally for a total of 8 weeks (from the 9th to 16th week).Fasting blood samples were collected for testing levels of fasting plasma glucose (FPG), triglycerides (TGs), total cholesterol (TC), free fatty acid (FFA), alanine aminotransferase (ALT), Acrp30 and insulin.Liver tissue was procured for histological examination.Expression of mRNA was detected by real-time RT-PC and of protein was detected by western blot analysis. RESULTS: The Ad-shAcrp30 treated mice had reduced expression of Acrp30 at both the mRNA and protein levels in adipose tissues and plasma, as compared with the AdshGFP treated mice (all P < 0.01).Compared to the WT and ApoE KO groups, the HF group showed higher levels of FPG, FFA, TGs and TC (all P < 0.01); furthermore, the Ad-shAcrp30 treatment compounded these changes.The Ad-shAcrp30 treated group had markedly higher hepatic TC and TGs than the HF group (P < 0.01 and P < 0.05).Oil Red O staining showed that there was more lipid droplets in the liver tissue of the Ad-shAcrp30 treated group than in that of the HF group (P < 0.01), and hematoxylin-eosin staining confirmed these results.Liraglutide treatment prevented the increase in body weight, FPG, FFA, TGs, TC and ALT levels, as compared to the saline controls (all P < 0.01), but the plasma Acrp30 levels and the Acrp30 mRNA and protein expression in adipose tissues were elevated (all P < 0.01).Oil-Red O staining indicated that the liraglutide group had a significantly lower hepatic lipid content than the saline group, and total hepatic TG and TC were reduced in the former group (P < 0.01 and P < 0.05).The liraglutide treatment significantly attenuated the mRNA expression of ACC and FAS (both P < 0.01) but increased AMPK phosphorylation (P < 0.01). CONCLUSION: Administration of liraglutide prevented the development of HFD-and hypoadiponectinemia-induced metabolic disturbance and accumulation of hepatic lipids in this mouse model system of NAFLD.