The p factor outweighs the specific internalizing factor in predicting recurrences of adolescent depression.

BACKGROUND: The early prediction of adolescent depression recurrence poses a significant challenge in the field. This study aims to investigate and compare the abilities of the general psychopathology factor (p) and the specific internalizing factor, in predicting depression recurrence over a 2-year course, as well as identifying remitted depressed adolescents from healthy adolescents. Longitudinal changes of these two factors in different trajectory groups were also tracked to examine their sensitivity to sustained remission and relapse. METHODS: We included 255 baseline-remitted depressed adolescents and a healthy control group (n = 255) matched in age, sex, and race, sourced from the Adolescent Brain Cognitive Development Study. The linear mixed model was employed for the statistical analysis. RESULTS: The p factor not only effectively discriminated between remitted depressed adolescents and healthy controls but also robustly predicted the depression recurrence over a subsequent 2-year course. The specific internalizing factor could only differentiate remitted depressed adolescents from healthy controls. Additionally, a noteworthy longitudinal decline of the p factor in the sustained-remission group was observed. CONCLUSIONS: Psychopathology factors serve as the inherent and enduring measurement of long-term mental health aberrations. Longitudinal results indicate that the p factor is more sensitive to respond to sustained remission than the internalizing factor. The ability of the overall p factor to anticipate depression relapse, unlike the specific internalizing factor, suggests the clinical interventions should monitor and mitigate the coincident symptoms across all dimensions to preempt relapse of adolescent depression, rather than an exclusive focus on internalizing symptoms.

Effects of fermented feed on growth performance, serum biochemical indexes, antioxidant capacity, and intestinal health of lion-head goslings.

Introduction: The aim of this study was to evaluate the effects of fermented feed on growth performance, antioxidant indexes and intestinal health in lion-head goslings. Methods: 288 male lion-head goslings (one-day-old) were randomly divided into four groups (6 replicates per group, 12 samples per replicate): control group (basal diet) and fermented feed (FF) groups (basal diet supplemented with 2.5, 5.0 and 7.5% FF, respectively). The experimental period lasted 28 days. Results: The results showed that 5.0 and 7.5% FF groups decreased feed conversion rate (FCR) when compared with the control group (p < 0.05). The 5.0% FF group reduced the activity of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in serum; while the 7.5% FF group decreased the concentration of total cholesterol (TC), ALP and LDH activity (p < 0.05). Furthermore, the 7.5% FF group significantly increased total antioxidant capacity (T-AOC) in serum (p < 0.05); 2.5% and 5.0% FF groups significantly increased glutathione peroxidase (GSH-Px) in serum (p < 0.05); all FF groups increased the activity of superoxide dismutase (T-SOD) in serum (p < 0.05). For intestinal health, the villous height and villi/crypt ratio in jejunum were increased in all FF groups, but crypt depth was decreased (p < 0.05); The 5.0% FF groups enhanced T-AOC activity in jejunum (p < 0.05); The 2.5% and 5.0% FF groups enhanced GSH-Px activity (p < 0.05) in jejunum; All FF groups reduced malondialdehyde (MDA) level in jejunum (p < 0.05). LEfSe analysis showed that the cecum microbiota was significantly dominant in the 2.5% FF group compared to the control group including Firmicutes, Lactobacillales, Lactobacillus, and Prevotella; the flora that were significantly dominant in the 5.0% FF group compared to the control group included Bacteroidaceae, Bacteroides, Megamonas, and Prevotella; and the groups that were significantly dominant in the 7.5% FF group compared to the control group included Bacteroidota, Bacteroides, Bacteroidaceae, and Ruminococcaceae. Discussion: In summary, dietary FF supplementation improved growth performance, serum biochemical parameters and antioxidant capacity of lion-head goslings, as well as improved jejunal tissue morphology and optimized intestinal flora structure. In particular, the FF addition at a dose of 7.5% was relatively more effective for lion- head goslings.

Vitamin D alleviates non-alcoholic fatty liver disease via restoring gut microbiota and metabolism.

Background: Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. Dysbiosis of gut microbiome has been identified as one of the key environmental factors contributing to NAFLD. As an essential nutrition, Vitamin D (VD) plays an important role in regulating gut microbiota based on its receptor (Vitamin D Receptor, VDR) which is highly expressed in the gastrointestinal tract. Methods: Rats were fed with HFD (high-fat diet) for 12 weeks. And the rats were treated with VD two times a week by intraperitoneal injection for 12 weeks. H&E staining combined with plasma biochemical index was performed to characterize pathological changes and function of the liver. Fecal microbiota 16S rRNA gene sequencing and metabolomics were taken to reveal the altered gut microbiota and metabolites. Result: The VD alleviates the HFD-induced lipid accumulation in the liver as well as decreases the levels of amlodipine besylate (ALT) and amlodipine aspartate (AST). VD supplement decreased the ratio of phylum Firmicutes/Bacteroidetes (F/B) but increased alpha diversity. In addition, the VD treatment improved the HFD-induced gut microbiota by increasing the Prevotella and Porphyromonadaceae and decreasing Mucispirillum, Acetatifactor, Desulfovibrio, and Oscillospira abundance. Furthermore, the capability of tyrosine metabolism, tryptophan metabolism, arginine biosynthesis, and sphingolipid metabolism was enhanced after VD treatment. Consistently, Prevotella positively correlated with tryptophan metabolism and sphingolipid metabolism. Importantly, the Prevotella abundance was positively associated with serotonin, melatonin, tryptamine, L-arginine, and 3-dehydrosphinganine which synthesize from tryptophan, tyrosine, arginosuccinate, and serine, respectively. Conclusion: VD treatment inhibited HFD-induced NAFLD accompany by dysbiosis gut microbiota and metabolites, suggesting that VD supplement could be a potential intervention used for NAFLD treatment by targeting the specific microbiota.

A Depression-Risk Mental Pattern Identified by Hidden Markov Model in Undergraduates.

Few studies have examined depression risk screening approaches. Universal depression screening in youth typically focuses on directly measuring the current distress and impairment by several kinds of depression rating scales. However, as many people have stigmatizing attitudes to individuals with depression, youths with depression were in fear of being known, and embarrassment held them back from reporting their depression symptoms. Thus, the present study aimed to identify the best, most easy access screening approach for indirectly predicting depression risks in undergraduates. Here, the depression score was ranked and viewed as the different stages in the development of depression; then, we used a Hidden Markov Model (HMM) approach to identify depression risks. Participants included 1247 undergraduates (female = 720, mean age = 19.86 years (std =1.31), from 17 to 25) who independently completed inventories for depressive symptoms, emotion regulation, subjective well-being (life satisfaction, negative and positive affect), and coping styles (positive and negative). Our findings indicated that the risk pattern (state 1) and the health pattern (state 2) showed distinct different rating results in emotional regulation, subjective well-being, and coping style. Screening for prospective risk of depression can be better accomplished by HMM incorporating subjective well-being, emotion regulation, and coping style. This study discussed the implications for future research and evidence-based decision-making for depression screening initiatives.

Scarcity Mindset Neuro Network Decoding With Reward: A Tree-Based Model and Functional Near-Infrared Spectroscopy Study.

Resource scarcity imposes challenging demands on the human cognitive system. Insufficient resources cause the scarcity mindset to affect cognitive performance, while reward enhances cognitive function. Here, we examined how reward and scarcity simultaneously contribute to cognitive performance. Experimental manipulation to induce a polar scarcity mindset and reward conditions within participants under functional near-infrared spectroscopy (fNIRS) recording was implemented to explore the mechanism underlying the scarcity mindset and reward in terms of behavior and neurocognition. Participants showed decreased functional connectivity from the dorsolateral prefrontal cortex (DLPFC) to the ventrolateral prefrontal cortex (VLPFC) with a scarcity mindset, a region often implicated in cognitive control. Moreover, under reward conditions, the brain activation of the maximum total Hb bold signal was mainly located in the left hemisphere [channels 1, 3, and 4, left ventrolateral prefrontal cortex (L-VLPFC) and channel 6, left dorsolateral prefrontal cortex (L-DLPFC)], and there was also significant brain activation of the right dorsolateral prefrontal cortex (R-DLPFC) in the right hemisphere (channel 17). Furthermore, these data indicate the underlying neural changes of the scarcity mentality and demonstrate that brain activities may underlie reward processing. Additionally, the base-tree machine learning model was trained to detect the mechanism of reward function in the prefrontal cortex (PFC). According to SHapley Additive exPlanations (SHAP), channel 8 contributed the most important effect, as well as demonstrating a high-level interrelationship with other channels.

Decarboxylated osteocalcin, a possible drug for type 2 diabetes, triggers glucose uptake in MG63 cells.

BACKGROUND: Uncarboxylated osteocalcin (GluOC) has been reported to improve glucose metabolism, prevent type 2 diabetes, and decrease the severity of obesity in mice with type 2 diabetes. GluOC can increase glucose uptake in a variety of cells. Glucose metabolism is the main source of energy for osteoblast proliferation and differentiation. We hypothesized that decarboxylated osteocalcin (dcOC), a kind of GluOC, can increase glucose uptake in MG63 cells (osteoblast-like osteosarcoma cells) and influence their proliferation and differentiation. AIM: To investigate the effects of dcOC on glucose uptake in human osteoblast-like osteosarcoma cells and the possible signaling pathways involved. METHODS: MG63 cells (human osteoblast-like osteosarcoma cells) were treated with dcOC (0, 0.3, 3, 10, or 30 ng/mL) for 1 and 72 h, and glucose uptake was measured by flow cytometry. The effect of dcOC on cell proliferation was measured with a CCK-8 assay, and alkaline phosphatase (ALP) enzyme activity was measured. PI3K was inhibited with LY294002, and hypoxia-inducible factor 1 alpha (HIF-1α) was silenced with siRNA. Then, GPRC6A (G protein-coupled receptor family C group 6 subtype A), total Akt, phosphorylated Akt, HIF-1α, and glucose transporter 1 (GLUT1) levels were measured by Western blot to elucidate the possible pathways by which dcOC modulates glucose uptake. RESULTS: The glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after short-term (1 h) treatment with dcOC at different concentrations (0.3, 3, and 10 ng/mL groups, P < 0.01; 30 ng/mL group, P < 0.05). Glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after long-term (72 h) treatment with dcOC at different concentrations (0.3, 3, and 10 ng/mL groups, P < 0.01; 30 ng/mL group, P < 0.05). DcOC triggered Akt phosphorylation in a dose-dependent manner, and the most effective stimulatory concentration of dcOC for short-term (1 h) was 3 ng/mL (P < 0.01). LY294002 abolished the dcOC-mediated (1 h) promotion of Akt phosphorylation and glucose uptake without affecting GLUT1 protein expression. Long-term dcOC stimulation triggered Akt phosphorylation and increased the protein levels of HIF-1α, GLUT1, and Runx2 in a dose-dependent manner. Inhibition of HIF-1α with siRNA abolished the dcOC-mediated glucose uptake and substantially decreased GLUT1 protein expression. DcOC intervention promoted cell proliferation in a time- and dose-dependent manner as determined by the CCK-8 assay. Treatment with both 3 ng/mL and 10 ng/mL dcOC affected the ALP activity in MG63 cells after 72 h (P < 0.01). CONCLUSION: Short- and long-term dcOC treatment can increase glucose uptake and affect proliferation and ALP activity in MG63 cells. This effect may occur through the PI3K/Akt, HIF-1α, and GLUT1 signaling factors.

Vitamin D ameliorates high-fat-diet-induced hepatic injury via inhibiting pyroptosis and alters gut microbiota in rats.

Accumulating evidence suggests that vitamin D (VD) has a therapeutic effect on non-alcoholic fatty liver disease (NAFLD). Pyroptosis and gut microbiota have been recognized as critical factors of the progression of NAFLD. However, the effect of VD on the pyroptosis and gut microbiota in NAFLD remains inconclusive. Herein, rats were fed high fat diet (HFD) for 12 weeks and concurrently treated with 5 µg/kg 1,25(OH)2D3 twice a week. BRL-3A cells were stimulated with 0.4 mmol/L palmitic acid (PA) and 1 µg/ml lipopolysaccharide (LPS) for 16 h and treated with 10-6 mol/L 1,25(OH)2D3. Effect of VD on the hepatic injury, lipid accumulation, activation of NLRP3 inflammasome and pyroptosis was determined in vivo and in vitro. Next, gasdermin D N-terminal (GSDMD-N) fragment was overexpressed in BRL-3A cells to investigate the role of pyroptosis in the therapeutic effect of VD on NAFLD. In addition, gut microbiota in NAFLD rats was also analyzed. Results showed that VD attenuated HFD-induced hepatic injury in vivo and PA-LPS-induced impairment of cell viability in vitro, and inhibited lipid accumulation, activation of NLRP3 inflammasome and pyroptosis in vivo and in vitro. GSDMD-N fragment overexpression suppressed the protective effect of VD on PA-LPS-induced activation of NLRP3 inflammasome, impairment of cell viability and lipid accumulation, indicating that VD might attenuate NAFLD through inhibiting pyroptosis. Additionally, VD also restored HFD-induced gut microbiota dysbiosis by increasing the relative abundance of Lactobacillus and reducing that of Acetatifactor, Oscillibacter and Flavonifractor. This study provides a novel mechanism underlying VD therapy against NAFLD.

Photocatalyzed Csp3-Csp3 cross-dehydrogenative coupling of N-Boc-tetrahydroisoquinolines with α,ß-unsaturated ketones.

A novel photocatalyzed cross-dehydrogenative coupling reaction of N-Boc-tetrahydroisoquinolines with α,ß-unsaturated ketones has been developed. This research provides an easy access to a variety of C1-substituted tetrahydroisoquinolines, which can be further transformed into benzo[a]-quinolizine-2-ones, the skeletons of natural products with a wide range of biological activities. The load of the photocatalyst is low and the oxidant is inexpensive and less toxic.

Clostridium butyricum Alleviates Gut Microbiota Alteration-Induced Bone Loss after Bariatric Surgery by Promoting Bone Autophagy.

Bariatric surgery is the most common and effective treatment of severe obesity; however, these bariatric procedures always result in detrimental effects on bone metabolism by underlying mechanisms. This study aims to investigate the skeletal response to bariatric surgery and to explore whether Clostridium butyricum alleviates gut microbiota alteration-induced bone loss after bariatric surgery. Consequently, male SD rats received Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) surgery, respectively, followed by body weight recording. The bone loss after bariatric surgery was further determined by dual-energy X-ray absorptiometry (DXA), micro-CT measurement, histologic analyses, and Western blot. Besides, 16S rDNA gene sequencing was performed to determine the gut microbiota alteration after surgery, and intervention with fecal microbiota from RYGB donor was conducted in obese SD rats, followed by C. butyricum administration. Accordingly, rats in the RYGB and SG groups maintained sustained weight loss, and DXA and micro-CT measurement further demonstrated significant bone loss after bariatric surgery. Besides, histologic and Western blot analyses validated enhanced osteoclastogenesis and inhibited osteoblastogenesis and defective autophagy after surgery. The 16S rDNA gene sequencing suggested a significant alteration of gut microbiota composition in the RYGB group, and intervention with fecal microbiota from RYGB donor further determined that this kind of alteration contributed to the bone loss after RYGB. Meanwhile, C. butyricum might protect against this postoperative bone loss by promoting osteoblast autophagy. In summary, this study suggests novel mechanisms to clarify the skeletal response to bariatric surgery and provides a potential candidate for the treatment of bone disorder among bariatric patients. SIGNIFICANCE STATEMENT: The significance of this study is the discovery of obvious bone loss and defective autophagy after bariatric surgery. Besides, it is revealed that gut microbiota alterations could be the reason for impaired bone mass after bariatric surgery. Furthermore, Clostridium butyricum could alleviate the gut microbiota alteration-induced bone loss after bariatric surgery by promoting osteoblast autophagy.

Liraglutide ameliorates lipotoxicity-induced inflammation through the mTORC1 signalling pathway.

Lipotoxicity has been implicated in many disease processes, and prolonged exposure to high lipid levels often leads to the activation of a variety of abnormal signals, which in turn leads to the induction of inflammation. The aim of our study was to explore the correlation between mammalian target of rapamycin (mTOR) and inflammation by studying high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats and palmitate (PA)-induced inflammation (lipotoxicity) in HepG2 cells. In addition, we investigated whether the glucagon-like peptide-1 (GLP-1) analogue liraglutide can protect rats and HepG2 cells from lipotoxicity. Our results showed that an HFD and PA significantly increased inflammation by activating the mTORC1 pathway in vitro and in vivo. Treatment with rapamycin (an mTOR inhibitor) inhibited some effects of PA on inflammation. Furthermore, we observed that liraglutide inhibited PA-induced inflammation by inactivating mTORC1 signalling molecules. Overall, our findings demonstrated that mTORC1 signalling pathways were involved primarily in high lipid level-induced inflammation. Importantly, liraglutide may protect against lipotoxicity-induced inflammation by regulating mTORC1-dependent pathways.

The preventive effect of liraglutide on the lipotoxic liver injury via increasing autophagy.

INTRODUCTION AND OBJECTIVES: The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing. Previous studies indicated that Liraglutide, glucagon-like peptide-1 analogue, could regulate glucose homeostasis as a valuable treatment for Type 2 Diabetes. However, the precise effect of Liraglutide on NAFLD model in rats and the mechanism remains unknown. In this study, we investigated the molecular mechanism by which Liraglutide ameliorates hepatic steatosis in a high-fat diet (HFD)-induced rat model of NAFLD in vivo and in vitro. MATERIALS AND METHODS: NALFD rat models and hepatocyte steatosis in HepG2 cells were induced by HFD and palmitate fatty acid treatment, respectively. AMPK inhibitor, Compound C was added in HepG2 cells. Autophagy-related proteins LC3, Beclin1 and Atg7, and AMPK pathway-associated proteins were evaluated by Western blot and RT-PCR. RESULTS: Liraglutide enhanced autophagy as showed by the increased expression of the autophagy markers LC3, Beclin1 and Atg7 in HFD rats and HepG2 cells treated with palmitate fatty acid. In vitro, The AMPK inhibitor exhibited an inhibitory effect on Liraglutide-induced autophagy enhancement with the deceased expression of LC3, Beclin1 and Atg7. Additionally, Liraglutide treatment elevated AMPK levels and TSC1, decreased p-mTOR expression. CONCLUSIONS: Liraglutide could upregulate autophagy to decrease lipid over-accumulation via the AMPK/mTOR pathway.

Methionine enkephalin (MENK) regulates the immune pathogenesis of type 2 diabetes mellitus via the IL-33/ST2 pathway.

The incidence and mortality of type 2 diabetes mellitus (T2DM) rank among the top ten worldwide. Emerging studies indicate pathological roles for the immune system in inflammation, insulin resistance and islet ß-cell damage in subjects with T2DM. Methionine enkephalin (MENK) is present in endocrine cells of the pancreas and has been suggested to be an important mediator between the immune and neuroendocrine systems. Therefore, it may play a role in modulating insulin secretion from islet cells. Since little is known about the effect of MENK on T2DM, therefore it was the aim of this study to characterize the role and possible mechanism of action of MENK on plasma glucose and serum insulin levels in T2DM rats and INS-1 cells in vivo and in vitro. MENK significantly decreased the plasma glucose level and increased the serum insulin concentration in T2DM rats. It also increased the serum levels of the cytokines IL-5 and IL-10, while decreased TNF-α and IL-2 levels. We further confirmed that MENK regulated glucose metabolism by upregulating opioid receptor expression and modulating the IL-33/ST2 and MyD88-TRAF6-NF-κB p65 signaling pathways. Based on these results, an intraperitoneal injection of MENK represents a potentially new approach for T2DM.

Glucagon-like peptide-1 preserves non-alcoholic fatty liver disease through inhibition of the endoplasmic reticulum stress-associated pathway.

AIM: Glucagon-like peptide-1 (GLP-1) has been increasingly recognized for treating diabetes mellitus, and for its potential to effectively treat non-alcoholic fatty liver disease (NAFLD). However, the mechanisms of GLP-1 induction in NAFLD are not completely known. We investigated whether GLP-1 can protect against NAFLD by alleviating endoplasmic reticulum (ER) stress. METHODS: Male Sprague-Dawley rats were fed a high-fat diet and treated with a long-acting GLP-1 receptor agonist, liraglutide. Biochemical, morphological, genetic and protein expression of ER stress were investigated. In vitro, HepG2 cells were exposed to 0.4 mM palmitate fatty acid and treated with different concentrations of GLP-1, and ER protein 46 (ERp46) and ER stress pathways were analyzed. Cellular response to ER stress and apoptosis were determined upon transfection with either ERp46 siRNA or a negative control siRNA. RESULTS: In vivo, the treatment of GLP-1 attenuated the hepatic accumulation of lipids, reduced inflammation and improved metabolic parameters. GLP-1 treatment significantly upregulated the expression of ERp46 and downregulated the ER stress marker. Activation of ER pathways was restrained by GLP-1. Similar observations were made in vitro. Furthermore, inhibition of ERp46 expression by siRNA-mediated silencing increased the ER stress response and enhanced cell apoptosis rates. In addition, GLP-1 could not reduce the levels of ER stress and apoptosis in cells transfected with ERp46 siRNA compared with in negative control transfected cells after palmitate treatment. CONCLUSION: GLP-1 protected against NAFLD by inactivating the ER stress-associated apoptosis pathway. In addition, the effect was possibly related to the signaling pathway of ERp46.

Protective effect of liraglutide against ER stress in the liver of high-fat diet-induced insulin-resistant rats.

The purpose of this study was to investigate whether the glucagon-like peptide-1 (GLP-1) analog liraglutide can alleviate endoplasmic reticulum (ER) stress and insulin resistance (IR) in the liver of high-fat diet-induced insulin-resistant rats. Eighty-five male Sprague-Dawley rats were fed with normal chow or a high-fat diet for 12 weeks. The IR was evaluated using the hyperinsulinemic-euglycemic clamp technique. The rats in the HF group were further divided into four groups and were treated with or without liraglutide by subcutaneous injection. Body weight (BW), fasting blood glucose (FBG), fasting insulin (FINS), and insulin sensitivity were measured. The expression of ER stress marker GRP78 and its signaling mediators, such as IRE1α, PERK, and ATF6, in the liver were examined. The ultrastructure of the ER in the liver was examined by transmission electron microscopy. The expression levels of chemerin in the liver and the serum were also measured. After 4 weeks of liraglutide treatment, the BW, FBG, and FINS levels were significantly reduced, and the insulin sensitivity was increased compared with the HF only rats. Liraglutide reduced the expression of GRP78 and chemerin in liver tissue at both the mRNA and protein levels. Interestingly, the chemerin mRNA was closely correlated with the level of GRP78 mRNA, while the level of chemerin in serum was also associated with the FINS level. As a representative GLP-1 analog, liraglutide can suppress ER stress and reduce chemerin expression in the liver of rats exposed to a high-fat diet.

[Influence of GLP-1 on oxidative stress injury in non-alcoholic fatty liver disease rats].

OBJECTIVE: To investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress injury using a rat model of non-alcoholic fatty liver disease. METHODS: Sixty male Sprague-Dawley rats were fed 12 weeks of either a diet of normal chow (NC), for use as controls (n =15) or high-fat chow (HF), for use as models (n =45).The NC rats were administered normal saline, while the HF rats were treated with either normal saline (NS), for use as untreated model controls (n =10), low-dose GLP-1 (LG, 50 mutg/kg; n =10), mid-dose GLP-1 (MG, 100 mutg/kg; n =10), or high-dose GLP-1 (HG, 200 mug/kg; n =10); all treatments lasted for 4 weeks.The rats' weight, levels of serum biochemical markers (triglycerides, total cholesterol, high-density lipoproteincholesterol, low-density lipoprotein-cholesterol, alanine arninotransferase, and aspartate aminotransferase), levels of superoxide dismutase (SOD) and malondialdehyde (MDA), and expression of CYP2E1 mRNA and protein in liver homogenates were measured.The F test, t-test, least significant difference test and Dunnett's T3 test were used for statistical analyses. RESULTS: Compared with the NC group, the rars in the NS group showed significantly lower SOD (165.81 ± 11.64 vs.192.89 ± 16.53 U/mg, P < 0.05), significantly higher MDA (7.30 ± 1.79 vs.3.10 ± 1.30 nmol/ mg, P < 0.05), and significantly higher expressions of CYP2E1 mRNA and protein (both P < 0.05).After GLP1 treatment, the rats in the LG, MG and HG groups showed increased levels of SOD (compared to the NS group; 171.44 ± 9.80 vs.177.66 ± 14.77 vs.186.17 ± 15.43 U/mg; only the HG group had P < 0.05), significantly decreased levels of MDA (compared to the NS group; 5.16 ± 1.45 vs.4.08 ± 1.22 vs.3.31 ± 1.14 nmol/mg; all P < 0.05], and decreased levels of CYP2E1 mRNA and protein expressions (CYP2E1 mRNA:only the HG group had P < 0.05; CYP2E1 protein: both the MG and HG groups had P < 0.05). CONCLUSION: GLP-1 treatment can improve oxidative stress injury, suggesting its potential as a therapeutic agent for non-alcoholic fatty liver disease.

Downregulation of chemerin and alleviation of endoplasmic reticulum stress by metformin in adipose tissue of rats.

AIMS: To investigate whether metformin regulates chemerin expression in vivo by alleviating ER stress. METHODS: Male Sprague-Dawley rats were fed a high-fat or normal diet for 10 weeks to induce insulin resistance. During the following 6 weeks, the rats were divided into four groups: normal diet without treatment (NC), normal diet with metformin treatment (NM), high-fat diet without metformin (HF), and high-fat diet with metformin (HM). Body weight, fasting glucose, basal insulin level, insulin sensitivity, chemerin expression in serum and adipose tissue, ER stress marker and its pathway were measured. RESULTS: After 6 weeks treatment, metformin reduced the body weight gain and enhanced insulin sensitivity of high-fat fed rats. The basal insulin level in the HM group was lower than in the HF group. Metformin reduced chemerin expression in the HM group compared with HF. Metformin reduced the GRP78 mRNA expression in HM rats. Activation of IRE1 alpha was lower in the HM group than the HF group. CONCLUSIONS: Metformin treatment decreased the chemerin expression and alleviated the ER stress in the visceral adipose tissue of high-fat diet-induced insulin-resistant rats. These data may also provide a further rationale for exploring the use of metformin in the treatment of insulin resistance.