Amelioration of ethanol-induced oxidative stress and alcoholic liver disease by in vivo RNAi targeting Cyp2e1.

Alcoholic liver disease (ALD) results from continuous and heavy alcohol consumption. The current treatment strategy for ALD is based on alcohol withdrawal coupled with antioxidant drug intervention, which is a long process with poor efficacy and low patient compliance. Alcohol-induced CYP2E1 upregulation has been demonstrated as a key regulator of ALD, but CYP2E1 knockdown in humans was impractical, and pharmacological inhibition of CYP2E1 by a clinically relevant approach for treating ALD was not shown. In this study, we developed a RNAi therapeutics delivered by lipid nanoparticle, and treated mice fed on Lieber-DeCarli ethanol liquid diet weekly for up to 12 weeks. This RNAi-based inhibition of Cyp2e1 expression reduced reactive oxygen species and oxidative stress in mouse livers, and contributed to improved ALD symptoms in mice. The liver fat accumulation, hepatocyte inflammation, and fibrosis were reduced in ALD models. Therefore, this study suggested the feasibility of RNAi targeting to CYP2E1 as a potential therapeutic tool to the development of ALD.

ACLY-ß-catenin axis modulates hepatoblastoma cell proliferation.

HB (hepatoblastoma) is most common in children with liver cancer and few options for treating HB. Thus, it is of great significance to investigate the regulatory mechanism of HB and/or identify new therapeutic targets for clinical treatment of HB. Here, we showed that ACLY (ATP citrate lyase), an important lipometabolic enzyme for de novo biosynthesis of fatty acids and steroids, has a higher expression in HB tissues than noncancerous tissues, and is required for HB cell proliferation. Moreover, knocking down ACLY in HB cells caused severe S-phase arrest and apoptosis. Mechanistically, ACLY knockdown significantly silenced the Wnt signaling pathway and reduced ß-catenin expression in HB cells. Conversely, the apoptotic alleviation of HB cells by overexpressing ACLY was blocked by silencing ß-catenin, suggesting the modulation of HB cells by ACLY-ß-catenin axis. Our results uncovered the role of ACLY in HB cells and presented a theoretical approach for HB targeted therapy in the future.

Neurodevelopmental trajectories, polygenic risk, and lipometabolism in vulnerability and resilience to schizophrenia.

BACKGROUND: Schizophrenia (SZ) arises from a complex interplay involving genetic and molecular factors. Early intervention of SZ hinges upon understanding its vulnerability and resiliency factors in study of SZ and genetic high risk for SZ (GHR). METHODS: Herein, using integrative and multimodal strategies, we first performed a longitudinal study of neural function as measured by amplitude of low frequency function (ALFF) in 21 SZ, 26 GHR, and 39 healthy controls to characterize neurodevelopmental trajectories of SZ and GHR. Then, we examined the relationship between polygenic risk score for SZ (SZ-PRS), lipid metabolism, and ALFF in 78 SZ, and 75 GHR in cross-sectional design to understand its genetic and molecular substrates. RESULTS: Across time, SZ and GHR diverge in ALFF alterations of the left medial orbital frontal cortex (MOF). At baseline, both SZ and GHR had increased left MOF ALFF compared to HC (P < 0.05). At follow-up, increased ALFF persisted in SZ, yet normalized in GHR. Further, membrane genes and lipid species for cell membranes predicted left MOF ALFF in SZ; whereas in GHR, fatty acids best predicted and were negatively correlated (r = -0.302, P < 0.05) with left MOF. CONCLUSIONS: Our findings implicate divergence in ALFF alteration in left MOF between SZ and GHR with disease progression, reflecting vulnerability and resiliency to SZ. They also indicate different influences of membrane genes and lipid metabolism on left MOF ALFF in SZ and GHR, which have important implications for understanding mechanisms underlying vulnerability and resiliency in SZ and contribute to translational efforts for early intervention.

Duplex Responsive Nanoplatform with Cascade Targeting for Atherosclerosis Photoacoustic Diagnosis and Multichannel Combination Therapy.

The culprits of atherosclerosis are endothelial damage, local disorders of lipid metabolism, and progressive inflammation. Early atherosclerosis is typically difficult to diagnose in time due to the lack of obvious symptoms, thus missing the best period of treatment. In this work, a π-conjugated polymer (PMeTPP-MBT) based on 3,6-bis(4-methylthiophen-2-yl)-2,5-bis(2-octyldodecyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione is designed as a novel photoacoustic contrast agent. On this basis, an intelligent responsive theranostic nanoplatform (PA/ASePSD) combining astaxanthin and SS-31 peptide and loading with PMeTPP-MBT is developed. The high affinity between the dextran shell with the broken endothelial surface VCAM-1 and CD44 confers active targeting of PA/ASePSD to atherosclerotic lesions. High levels of ROS in the acidic plaque microenvironment act as an intelligent cascade switch to achieve controlled release of astaxanthin, SS-31 peptide, and PMeTPP-MBT for non-invasive photoacoustic diagnosis, as well as plaque inhibition mediated by anti-inflammation and multichannel regulation (including ABCA1, ABCG1, CD36, and LOX-1) of lipid metabolism. Both in vitro and in vivo evaluations confirm the impressive anti-atherosclerotic capability and the accurate photoacoustic diagnosis of PA/ASePSD nanoparticles, thus promising a candidate for early-stage atherosclerosis theranostics.

Clinical value of circ-PNPT1 on adverse pregnancy outcomes of patients with gestational diabetes mellitus.

OBJECTIVE: Several circular RNAs are associated with important pathophysiological characteristics of gestational diabetes mellitus (GDM). This study intended to measure the expression of circ-PNPT1 in sera of GDM patients and to expound on its values on pregnancy outcomes.

Methods: About 104 GDM patients and 71 healthy controls were recruited. The expression pattern of serum circ-PNPT1 was measured by reverse transcription-quantitative polymerase chain reaction. The diagnostic efficacy of circ-PNPT1 and fasting blood glucose (FBG) on GDM was evaluated by receiver operating characteristic (ROC) analysis. Parameters of glycolipid metabolism were determined using automatic biochemical analyzers. The correlation between circ-PNPT1 and glycolipid metabolism parameters was analyzed using Pearson analysis. GDM patients were divided into a high expression group and a low expression group based on the median value of circ-PNPT1 expression. Curves of adverse neonatal outcomes were drawn by Log Rank analysis.

Results: GDM patients exhibited higher circ-PNPT1 expression than healthy controls. The area under the ROC curve of circ-PNPT1 diagnosing GDM was 0.9184 and the cut-off value was 1.435 (90.38% sensitivity, 85.92% specificity). Serum circ-PNPT1 expression was positively correlated with FBG, total cholesterol, and triglyceride in GDM patients. Neonates born to GDM patients with high circ-PNPT1 expression were prone to adverse outcomes.

Conclusion: Circ-PNPT1 was highly-expressed in the sera of GDM patients. Circ-PNPT1 affected glycolipid metabolism and its expression had certain reference values on adverse pregnancy outcomes.

Annexin A6 Polymorphism Is Associated with Pro-atherogenic Lipid Profiles and with the Downregulation of Methotrexate on Anti-Atherogenic Lipid Profiles in Psoriasis.

BACKGROUND: Annexin A6 (AnxA6) is a lipid-binding protein that regulates cholesterol homeostasis and secretory pathways. However, the correlation of AnxA6 polymorphism with lipometabolism has never been studied in psoriasis. OBJECTIVES: To investigate the impact of AnxA6 polymorphism on lipid profiles and the expression of AnxA6 protein in both peripheral blood mononuclear cells (PBMCs) and lipometabolism in psoriasis. METHODS: A total of 265 psoriatic patients received methotrexate (MTX) treatment for 12 weeks, after which their lipid profiles were determined by measuring total cholesterol (TC), triglycerides (TGs), lipoprotein (a) [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein (a)1 (ApoA1), and apolipoprotein B (ApoB). In addition, AnxA6 (rs11960458) was genotyped in 262 patients and the expression of AnxA6 in PBMCs was measured by Western blotting at baseline and week 8 post-MTX treatment. RESULTS: The CC genotype carriers of rs11960458 had a lower expression of AnxA6 and lower levels of the pro-atherogenic lipids TC, LDL, and ApoB compared to TC genotype carriers. MTX significantly downregulated the levels of the anti-atherogenic lipids HDL-C and ApoA1 and the level of AnxA6 in TC genotype carriers, as well as the level of TGs in CC genotype carriers. CONCLUSIONS: The polymorphism of AnxA6, rs11960458, was statistically associated with the levels of pro-atherogenic lipids and with the downregulation of MTX on the levels of anti-atherogenic lipids and TGs in psoriasis.

Novel lipometabolism biomarker for chemotherapy and immunotherapy response in breast cancer.

Emerging proof shows that abnormal lipometabolism affects invasion, metastasis, stemness and tumor microenvironment in carcinoma cells. However, molecular markers related to lipometabolism have not been further established in breast cancer. In addition, numerous studies have been conducted to screen for prognostic features of breast cancer only with RNA sequencing profiles. Currently, there is no comprehensive analysis of multiomics data to extract better biomarkers. Therefore, we have downloaded the transcriptome, single nucleotide mutation and copy number variation dataset for breast cancer from the TCGA database, and constructed a riskScore of twelve genes by LASSO regression analysis. Patients with breast cancer were categorized into high and low risk groups based on the median riskScore. The high-risk group had a worse prognosis than the low-risk group. Next, we have observed the mutated frequencies and the copy number variation frequencies of twelve lipid metabolism related genes LMRGs and analyzed the association of copy number variation and riskScore with OS. Meanwhile, the ESTIMATE and CIBERSORT algorithms assessed tumor immune fraction and degree of immune cell infiltration. In immunotherapy, it is found that high-risk patients have better efficacy in TCIA analysis and the TIDE algorithm. Furthermore, the effectiveness of six common chemotherapy drugs was estimated. At last, high-risk patients were estimated to be sensitive to six chemotherapeutic agents and six small molecule drug candidates. Together, LMRGs could be utilized as a de novo tumor biomarker to anticipate better the prognosis of breast cancer patients and the therapeutic efficacy of immunotherapy and chemotherapy.

Effects of exercise training in hypoxia versus normoxia on fat-reducing in overweight and/or obese adults: A systematic review and meta-analysis of randomized clinical trials.

Objective: Fat loss theory under various oxygen conditions has been disputed, and relevant systematic review studies are limited. This study is a systematic review and meta-analysis to assess whether hypoxic exercise training (HET) leads to superior fat-reducing compared with normoxic exercise training (NET). Methods: We searched PubMed, Web of Science, CNKI, ProQuest, Google Scholar, Cochrane Library, and EBSCOhost from inception to June 2022 for articles comparing the effects of hypoxic and normoxic exercise on body composition indicators, glycometabolism, and lipometabolism indicators in obese and overweight adults. Only randomized controlled trials (RCTs) were included. The effect sizes were expressed as standardized mean difference (SMD) and 95% confidence intervals (CI). Between-study heterogeneity was examined using the I 2 test and evaluated publication bias via Egger's regression test. The risk of bias assessment was performed for each included trial using Cochrane Evaluation Tool second generation. The meta-analysis was performed by using R 4.1.3 and RevMan 5.3 analytic tools. Results: A total of 19 RCTs with 444 subjects were analyzed according to the inclusion and exclusion criteria. Among them, there were 14 English literature and five Chinese literature. No significant difference in body composition (SMD -0.10, 95% CI -0.20 to -0.01), glycometabolism and lipid metabolism (SMD -0.01, 95% CI -0.13 to -0.10) has been observed when comparing the HET and NET groups. We only found low heterogeneity among trials assessing glycometabolism and lipometabolism (I 2 = 20%, p = 0.09), and no publication bias was detected. Conclusion: The effects of HET and NET on fat loss in overweight or obese people are the same. The application and promotion of HET for fat reduction need further exploration.

Influence of dietary fermented Folium mori on growing performance, lipometabolism and disease resistance of golden pompano Trachinotus ovatus.

Folium mori, as a plant unconventional feedstuff, are comparatively available due to cost-effectiveness, whereas their usage as aquafeed in pure form is restricted owing to the great fibre and antinutritional factors (ANFs) levels. Thereof, several methods of processing are introduced to remove antinutrient factors from the plant products, leading to improvement of bioactivity and digestibility. The assay was completed to evaluate the method of fermentation and the role of dietary fermented Folium mori (FFM) in golden pompano. Each of 5 diets with FFM at contents of 0.0%, 2.0%, 4.0%, 6.0% and 8.0% (D0.0, D2.0, D4.0, D6.0 and D8.0) was fed to the fishes with original body weight of 9.02g in triplicate sea cages for 56 days. The outcomes revealed that FFM in D4.0 and D6.0 elevated the growing performance of the fishes and the growing performance of D4.0 was remarkably improved in contrast to D0.0 and D2.0(P < 0.05). Whole body lipidic levels were obviously elevated when the diet FFM contents were below 8.0% (P < 0.05), whereas the contents of muscular moisture were generally reduced. In addition, FFM significantly increased serum high density lipoprotein (HDL) and remarkably reduced overall triglyceride (TG) in D2.0 to D6.0(P < 0.05). Moreover, FFM remarkably elevated the activities of lipase of stomach and hepatopancreas in contrast to D0.0 (P < 0.05) as well as intestinal tryptic enzyme in the entire FFM groups (P < 0.05). Eventually, FFM remarkably ameliorated disease-resistant characters of golden pompano to Vibrio harveyi in D4.0 and D6.0 (P < 0.05) and the RPS in D4.0 was optimal. To sum up, the present research displayed favorable role of FFM in growing performance, digestion, lipometabolism and disease-resistant characters, and the recommendation as to the supplementation content of diet FFM in compound feed of juvenile golden pompano is 4.0% as per the experiment status herein.

Oral administration of branched-chain amino acids ameliorates high-fat diet-induced metabolic-associated fatty liver disease via gut microbiota-associated mechanisms.

Branched-chain amino acids (BCAAs), essential amino acids for the human body, are mainly obtained from food. High levels of BCAAs in circulation are considered as potential markers of metabolic-associated fatty liver disease (MAFLD) in humans. However, there are conflicting reports about the effects of supplement of BCAAs on MAFLD, and research on BCAAs and gut microbiota is not comprehensive. Here, C57BL/6J mice were fed with a high-fat diet with or without BCAAs to elucidate the effects of BCAAs on the gut microbiota and metabolic functions in a mouse model of MAFLD. Compared to high-fat diet (HFD) feeding, BCAA supplementation significantly reduced the mouse body weight, ratio of liver/body weight, hepatic lipid accumulation, serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT), and the expressions of the lipogenesis-related enzymes Fas, Acc, and Scd-1 and increased expressions of the lipolysis-related enzymes Cpt1A and Atgl in the liver. BCAAs supplementation also counteracted HFD-induced elevations in serum BCAAs levels by stimulating the enzymatic activity of BCKDH. Furthermore, BCAAs supplementation markedly improved the gut bacterial diversity and altered the gut microbiota composition and abundances, especially those of genera, in association with MAFLD and BCAAs metabolism. These data suggest that BCAA treatment improves HFD-induced MAFLD through mechanisms involving intestinal microbes.

Function of Chick Subcutaneous Adipose Tissue During the Embryonic and Posthatch Period.

Since excess abdominal fat is one of the main problems in the broiler industry for the development of modern broiler and layer industry, the importance of subcutaneous adipose tissue has been neglected. However, chick subcutaneous adipose tissue appeared earlier than abdominal adipose tissue and more than abdominal adipose tissue. Despite a wealth of data, detailed information is lacking about the development and function of chick subcutaneous adipose tissue during the embryonic and posthatch period. Therefore, the objective of the current study was to determine the developmental changes of adipocyte differentiation, lipid synthesis, lipolysis, fatty acid ß-oxidation, and lipid contents from E12 to D9.5. The results showed that subcutaneous adipose tissue was another important energy supply tissue during the posthatch period. In this stage, the mitochondrial copy number and fatty acid ß-oxidation level significantly increased. It revealed that chick subcutaneous adipose tissue not only has the function of energy supply by lipidolysis but also performs the same function as brown adipose tissue to some extent, despite that the brown adipose tissue does not exist in birds. In addition, this finding improved the theory of energy supply in the embryonic and posthatch period and might provide theoretical basis on physiological characteristics of lipid metabolism in chicks.

Glycemic control by umbilical cord-derived mesenchymal stem cells promotes effects of fasting-mimicking diet on type 2 diabetic mice.

BACKGROUND: Hepatic steatosis is a big hurdle to treat type 2 diabetes (T2D). Fasting-mimicking diet (FMD) has been shown to be an effective intervention in dyslipidemia of T2D. However, fasting may impair the normal glucose metabolism. Human umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation has been discovered to regulate immune reactions and reduce hyperglycemia in diabetes. However, the effect of UC-MSCs on improving the lipid metabolism disorder is not quite satisfactory. We have investigated the efficacy comparison and interaction between FMD and UC-MSC infusion, aiming to establish effective T2D therapies and explore its mechanism. METHODS: C57/BL6 mice were fed with high-fat diet (HFD) to induce a diet-induced obese (DIO) mouse model. Leptin receptor-deficient (db/db) mice were used for follow-up experiments. DIO or db/db mice were divided into 4 groups: phosphate buffer saline (PBS), UC-MSCs, FMD, and UC-MSCs + FMD. At the end of the study period, mice were fasted and sacrificed, with the measurement of physiological and biochemical indexes. In addition, the fresh liver, skin, and white adipose tissue were analyzed by histology. RESULTS: FMD restored the lipid metabolism in DIO mice, whereas its capacity to rescue hyperglycemia was uncertain. Infusion of UC-MSCs was effective in T2D glycemic control but the impact on dyslipidemia was insufficient. Furthermore, both the glucose and the lipid alterations of DIO and db/db mice recovered after UC-MSCs combined with FMD. It was proved that UC-MSCs promoted FMD effects on ameliorating hyperglycemia and restoring the lipid metabolism in T2D mice, while FMD had little promotion effect on UC-MSCs. Mechanistically, we discovered that UC-MSC infusion significantly modulated systematic inflammatory microenvironment, which contributed to concerted actions with FMD. CONCLUSIONS: We established a strategy that combined UC-MSC infusion and FMD and was effective in treating T2D, which provided potential approaches for developing novel clinical T2D therapies.

Excessive Dietary Lipid Affecting Growth Performance, Feed Utilization, Lipid Deposition, and Hepatopancreas Lipometabolism of Large-Sized Common Carp (Cyprinus carpio).

An 82-day study was conducted to assess the effect of the dietary lipid levels on growth performance, feed utilization, lipid deposition, and hepatopancreas lipometabolism of large-sized common carp (Cyprinus carpio). Six isonitrogenous (300 g/kg protein) pelletized diets with different dietary lipid levels (30, 60, 90, 120, 150, and 180 g/kg) were fed in triplicate to fish groups with 75 individuals (with an initial mean weight of 247.00 ± 16.67 g). The results showed that there was a significant increase in weight gain (WG) rate (WGR), specific growth rate (SGR), and protein efficiency ratio (PER) as dietary lipid levels increased from 30 to 60 g/kg (p < 0.05) and then there was a decline. Feed conversion rate (FCR) was observed to be significantly lower in 60 g/kg lipid treatments (p < 0.05). Muscle crude protein contents were obtained to be significantly higher in 60 and 90 g/kg treatments (p < 0.05). The crude lipid content in the hepatopancreas increased significantly with an increase in dietary lipid levels (p < 0.05). The expression of lipoprotein lipase (LPL) and carnitine palmitoyltransferase-1 (CPT1) in the hepatopancreas was significantly downregulated with an increase in dietary lipid levels while the expression of growth hormone (GH), insulin-like growth factor-1 (IGF-1), fatty acid synthase (FAS), acetyl-CoA carboxylase-1 (ACC-1), and sterol regulatory element binding protein (SREBP) was upregulated first in 30 and 60 g/kg lipid treatments and then downregulated significantly in other treatments. The results revealed that excess dietary lipid supplements (more than 60 g/kg) would inhibit WG and would aggravate the lipid decomposition in the hepatopancreas. Based on WGR and FCR, the dietary lipid levels of 59.5 and 70.4 g/kg were optimal for growth performance and feed utilization of large-sized common carp.

The Roles and Pharmacological Effects of FGF21 in Preventing Aging-Associated Metabolic Diseases.

With the continuous improvement of living standards but the lack of exercise, aging-associated metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) are becoming a lingering dark cloud over society. Studies have found that metabolic disorders are near related to glucose, lipid metabolism, and cellular aging. Fibroblast growth factor 21 (FGF21), a member of the FGFs family, efficiently regulates the homeostasis of metabolism and cellular aging. By activating autophagy genes and improving inflammation, FGF21 indirectly delays cellular aging and directly exerts anti-aging effects by regulating aging genes. FGF21 can also regulate glucose and lipid metabolism by controlling metabolism-related genes, such as adipose triglyceride lipase (ATGL) and acetyl-CoA carboxylase (ACC1). Because FGF21 can regulate metabolism and cellular aging simultaneously, FGF21 analogs and FGF21 receptor agonists are gradually being valued and could become a treatment approach for aging-associated metabolic diseases. However, the mechanism by which FGF21 achieves curative effects is still not known. This review aims to interpret the interactive influence between FGF21, aging, and metabolic diseases and delineate the pharmacology of FGF21, providing theoretical support for further research on FGF21.

Acetate stimulates lipogenesis via AMPKα signaling in rabbit adipose-derived stem cells.

Acetate plays an important role in host lipid metabolism. However, the regulatory network underlying acetate-regulated lipometabolism remains unclear. The aim of this study was to determine whether any cross talk occurs among adenosine 5'-monophosphate-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPKs) and acetate in regulating lipid metabolism. The compound C (an AMPK inhibitor), and SB203580 (a p38 MAPK inhibitor) were used to treat rabbit adipose-derived stem cells (ADSCs) with or without acetate, respectively. It indicated that acetate (6 mM) for 6 h increased the lipid deposition in rabbit ADSCs. Besides, acetate treatment (6 mM) increased significantly phosphorylated protein level of AMPKα and p38 MAPK, but not altered significantly the phosphorylated protein level of extracellular signaling-regulated kinase (ERK) and c-Jun aminoterminal kinase (JNK). The blocking of AMPKα signaling attenuated acetate-induced lipid accumulation, but not that of p38 MAPK signaling. In conclusion, our findings suggest that AMPKα signaling pathway is associated with acetate-induced lipogenesis.

Effects of different diet-induced postnatal catch-up growth on glycolipid metabolism in intrauterine growth retardation male rats.

A number of studies have reported the occurrence of long-term metabolic disorders in mammals following intrauterine growth retardation (IUGR). However, the effects of dietary patterns during IUGR have not been fully elucidated. The present study aimed to evaluate the effects of different dietary patterns during critical growth windows on metabolic outcomes in the offspring of rats with IUGR. Male offspring rats from mothers fed either a normal or low-protein diet were randomly assigned to one of the following groups: Normal diet throughout pregnancy, lactation and after weaning (CON); normal diet throughout pregnancy and high-fat diet throughout lactation and after weaning (N + H + H); low-protein diet throughout pregnancy and high-fat diet throughout lactation and after weaning (IUGR + H + H); low-protein diet throughout pregnancy and lactation and high-fat diet after weaning (IUGR + L + H); and low-protein diet throughout pregnancy and normal diet throughout lactation and after weaning. During lactation, the male offspring in the N + H + H group exhibited the fastest growth rate, whereas the slowest rate was in the IUGR + L + H group. Following weaning, all IUGR groups demonstrated significant catch-up growth. Abnormal insulin tolerance were observed in the N + H + H, IUGR + H + H and IUGR + L + H groups and insulin sensitivity was decreased in IUGR + L + H group. The triglycerides/high-density lipoprotein ratio in the IUGR + L + H group was significantly higher compared with in the other groups. The abdominal circumference, Lee's index and adipocyte diameter of IUGR groups were significantly increased compared with the CON group. High levels of leptin and interleukin-6 in adipose tissues, and low adiponectin were observed in the IUGR + L + H group. Different dietary patterns during specific growth windows showed numerous impacts on glycolipid metabolism in IUGR offspring. The present study elucidated the mechanisms and potential options for IUGR treatment and prevention.

The modification of ferroptosis and abnormal lipometabolism through overexpression and knockdown of potential prognostic biomarker perilipin2 in gastric carcinoma.

BACKGROUND: To investigate the biological relationship, mechanism between perilipin2 and the occurrence, advancement of gastric carcinoma, and explore the mechanism of lipid metabolism disorder leading to gastric neoplasm, and propose that perilipin2 is presumably considered as a potential molecular biomarker of gastric carcinoma. METHODS: RNA-seq was applied to analyze perilipin2 and differentially expressed genes modulated by perilipin2 in neoplastic tissues of both perilipin2 overexpression and knockdown groups in vivo. The mechanism was discovered and confirmed by Rt-qPCR, immunoblotting, immunohistochemistry, staining and microassay, respectively. Cellular function experiments were performed by flow cytometry, CCK8, clonogenic assay, etc. RESULTS: Overexpression and knockdown of perilipin2 augmented the proliferation and apoptosis of gastric carcinoma cell lines SGC7901 and MGC803, respectively. The neoplastic cells with perilipin2-overexpression obtained more conspicuously rapid growth than knockdown group in vivo, and perilipin2 affected the proliferation and apoptosis of gastric carcinoma cells by modulating the related genes:acyl-coa synthetase long-chain family member 3, arachidonate 15-lipoxygenase, microtubule associated protein 1 light chain 3 alpha, pr/set domain 11 and importin 7 that were participated in Ferroptosis pathway. Moreover, RNA-seq indicated perilipin2 was an indispensable gene and protein in the suppression of Ferroptosis caused by abnormal lipometabolism in gastric carcinoma. CONCLUSION: Our study expounded the facilitation of perilipin2 in regulating the proliferation and apoptosis of gastric carcinoma cells by modification in Ferroptosis pathway, and we interpreted that the mechanism of gastric neoplasm caused by obesity, we also discovered that pr/set domain 11 and importin 7 are novel transcription factors relevant to gastric carcinoma. Furthermore, perilipin2 probably serves not only as a diagnostic biomarker, but also a new therapeutic target.

The Treatment of Prednisone in Mild Diabetic Rats: Biochemical Parameters and Cell Response.

BACKGROUND: Limited studies have been carried out with prednisone (PRED) in treatment by glucose intolerant individuals, even in this model the animals presented low blood glucose levels at adulthood, by the high regenerative capacity of ß-cell. OBJECTIVE: The aim was to evaluate the effects of the treatment of PRED in mild diabetes on biochemical and immunological biomarkers. METHODS: Rats were randomly divided into four groups: control (C), treated control C+PRED (treatment of 1.25 mg/Kg/day PRED); diabetic DM (mild diabetes) and treated diabetic DM+PRED (treatment with same dose as C+PRED group). Untreated groups received vehicle, adjusted volume to body weight. The treatment lasted 21 days and measured body weight, food and water intake, and glycemia weekly. In the 3rd week, the Oral Glucose Tolerance Test (OGTT) and the Insulin Tolerance Test (ITT) was performed. On the last day, the rats were killed and the blood was collected for biochemical analyzes, leukogram and immunoglobulin G levels. RESULTS: There was a significant decrease in body weight in mild diabetes; however, the treatment in diabetic groups increased food intake, glycemia, and the number of total leukocytes, lymphocytes and neutrophils. On the other hand, it decreased the levels of triglycerides, high-density and very lowdensity lipoproteins. In addition, diabetic groups showed glucose intolerance and mild insulin resistance, confirming that this model induces glucose intolerant in adult life. CONCLUSION: The results showed that the use of prednisone is not recommended for glucose intolerant individuals and should be replaced in order to not to aggravate this condition.

SEIPIN overexpression in the liver may alleviate hepatic steatosis by influencing the intracellular calcium level.

SEIPIN deficiency leads to a severe lipodystrophic phenotype with loss of fat tissue. Interestingly, SEIPIN knockout in non-adipocytes is reported to promote intracellular triacylglycerol (TG) accumulation. However, the underlying mechanisms remain unclear at present. Here, we have shown that SEIPIN knockdown and overexpression exert opposite effects on hepatic lipometabolism. Our experimental data suggest that depletion of SEIPIN induces an increase in intracellular TG via activation of ER stress while its overexpression triggers a decrease in the intracellular TG content via increasing PGC-1α, which drives increased mitochondrial activity. Adeno-associated virus-mediated SEIPIN overexpression alleviated high fat diet-induced hepatosteatosis in mice. The collective results indicate that the effects of SEIPIN on TG and PGC-1α are dependent on calcium concentrations, signifying regulatory activity on hepatic lipometabolism through alterations in the intracellular calcium level, and support the potential utility of modulating intracellular SEIPIN and calcium levels as novel therapeutic strategies for fatty liver.