Dyslipidemia In Mice Research Articles

Cmpk2 Gene and Protein Expression in Saliva or Salivary Glands of Dyslipidemic Mice

Salivary biomarkers are promising molecules for diagnosing systemic diseases. Cytidine/uridine monophosphate kinase 2 (CMPK2) is associated with various systemic diseases. However, little is known about the role of the CMPK2 gene in saliva and dyslipidemia. This study investigated the relationship between serum lipid levels and Cmpk2 mRNA expression in the saliva of dyslipidemic mice. Additionally, immunofluorescence staining was employed to assess the localization of the CMPK2 protein in the submandibular gland. Two types of dyslipidemic mice were utilized: mice fed a high-fat and high-cholesterol (HFHC) diet and genetically dyslipidemic ApoE-deficient mice. The mice at 9 to 46 weeks were analyzed for serum lipid levels, Cmpk2 mRNA expression in saliva, and CMPK2 protein localization in the submandibular glands. Both dyslipidemic mice displayed elevated low-density lipoprotein cholesterol and total cholesterol in serum. ApoE-deficient mice apparently exhibited increased Cmpk2 expression in saliva. Immunofluorescence staining indicated that CMPK2 proteins were primarily localized in the serous acini, potentially associated with the secretion of Cmpk2 mRNA in saliva. These findings suggest that Cmpk2 mRNA increases and is detectable in the saliva of dyslipidemic mice, providing a viable experimental model to assess the potential use of CMPK2 as a biomarker for dyslipidemia.

Impact of immune system humanization on atherosclerosis in dyslipidemic immunocompromised mice

Impact of immune system humanization on atherosclerosis in dyslipidemic immunocompromised mice

Characterization of a novel dyslipidemic immunodeficient mouse model for human immune cell engraftment studies

Characterization of a novel dyslipidemic immunodeficient mouse model for human immune cell engraftment studies

Anti-dyslipidemic effects of Pueraria lobata root and Glycine max (L.) Merrill extracts fermented with Lactiplantibacillus plantarum in ovariectomized mice.

Pueraria lobata root and Glycine max (L.) Merrill are rich in phytoestrogens. However, these bioactive ingredients have limited bioavailability due to their high molecular weight. In this study, we extracted two natural products and fermented with Lactiplantibacillus plantarum before mixing the fermented extracts (FPE-FGE). To understand whether FPE-FGE could alleviate menopause with dyslipidemia, we examined their effects on ovariectomy (OVX)-induced dyslipidemia in mice. Oral administration of the FPE-FGE (1:9, 3:7, and 9:1) did not affect safety-related biomarkers, such as uterus index (%), vagina index (%), aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine. Furthermore, FPE-FGE (1:9, 3:7, and 9:1) increased the levels of 17β-estradiol (E2) and expression of uterus estrogen receptor β (ERβ); there was little effect on the expression of uterus estrogen receptor α (ERα), and reduced the levels of gonadotropins, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). However, only the FPE-FGE (3:7) reduced the levels of blood lipids, including total cholesterol (TC) and LDL-cholesterol (LDL-C). Accordingly, FPE-FGE (3:7) upregulated endothelial nitric oxide synthase (eNOS), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG). In conclusion, FPE-FGE (3:7) attenuated themenopausal dyslipidemia by upregulating eNOS-NO-cGMP signaling pathway.

Variation in body weight, glucose/insulin tolerances, blood lipids and liver enzymes in mice in response to a high-fat-diet from lard

It raises questions about the impact of lard on the health and the differences in individual responses. Therefore, we developed a model of mice fed with high fat (HF) from lard in 130 days. The weight of the mice was measured every two days. Glucose tolerance test and insulin tolerance tests were performed at 70 days and 130 days of experiment. At the end of the study, the fat tissue was collected to check the weight, and a blood sample was collected to check the blood lipids and liver enzymes. Surprisingly, mice responded variously to the HF by being classified into two groups, one group had significantly high gained weight (HG_HF) versus the mice fed a standard diet (STD) (p < 0.001), and another group (LG_HF) has not difference in body weight compared to the STD groups. This phenomenon in body weight is directly reflected by the white fat accumulation, but not by brown fat. Eating HF from lard for a long time can disrupt glucose tolerance and cause dyslipidemia in mice, even in the LG_HF group, but can not disrupt insulin tolerance and cause liver enzyme disorders. In summary, our findings are a wake-up call for many cases where eating HF from lard does not gain weight and not increase the white fat storage, but still has the potential to cause adverse health effects. Further studies are encouraged to understand the molecular mechanisms that causes the body to regulate its weight and responses when eating HF from lard, especially in the LG_HF group.

A combination of metabolomics and microbiome analyses reveal the modulation of lipid metabolism effect of Nannochloropsis gaditana polysaccharides on alcohol-induced dyslipidemia in mice

Mining the nutritional function of Nannochloropsis gaditana is crucial for its development and utilization. This study evaluated the protective effect of purified Nannochloropsis gaditana polysaccharides (NPS) on alcohol-induced dyslipidemia. The study used a liquid alcohol diet and an NPS intervention of 200 mg/kg.bw and 400 mg/kg.bw for 5 weeks. Compared with the model group (MC), the NPS group had a lower triglyceride (TG) and total cholesterol (TC). The relative abundance of probiotics Akkermansia, Bifidobacterium and Ligilactobacillus were significantly higher in NPS groups than those in the model group. Compared with the MC, NPS group had higher serum phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio and lower ceramide. Moreover, the expression of lipidolysis-related genes such as PGC1α and CPT-1A in the NPS group were significantly higher compared to MC. In summary, NPS attenuated ethanol-induced dyslipidemia probably by regualating gut bateria and serum metabolites, which could serve as a potential prebiotic.

Impact of immune system humanization on atherosclerosis in dyslipidemic immunocompromised mice

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Cariplo Foundation. PRIN (Italian Ministry of University and Research) Background and aim Given the key role of immune response during atherosclerosis and the therapeutic interest on biologics targeting human immune cells, the need of experimental models to translate molecular mechanisms and test therapeutic approaches for atherosclerosis is continuously increasing. Here we provide an immune and metabolic characterization of an innovative immunodeficient mouse humanized with human hematopoietic cells on an atheroprone background. Methods LDLR-KO mice were crossed with the immunodeficient C57BL/6J strain Rag2-KO/IL2rg-KO/CD47-KO (TKO, IMSR_JAX:025730) to generate an immunocompromised dyslipidemic mouse (TKO-LDLR KO mice) recipient of human hematopoietic stem cells (hCD34+). Results TKO-LDLR KO were first characterized for their immune and metabolic profile. TKO mice are deficient in mature lymphocytes and NK cells and this profile was conserved in TKO-LDLR KO mice. Under high cholesterol diet, TKO-LDLR KO present monocytosis with increased levels of Ly6Chi monocytes compared to TKO-LDLR KO at standard diet, develop marked dyslipidemia, steatosis and atherosclerosis. This profile confirms the suitability of TKO-LDLR KO mice for atherosclerosis studies. Next we tested the impact of immune system humanization on atherosclerosis. TKO-LDLR KO pups received a low-dose irradiation (200 cGy) and thereafter 2 x 10^5 hCD34+ were injected in the liver. Engraftment of human leukocytes (hCD45+) was evaluated after two months by flow cytometry analysis from tail blood. This approach allows to reconstitute between 10-30% of hCD45+, mainly B and T cells. The humanization with hCD34+ cells worsens atherosclerosis development as compared to non-humanized TKO-LDLR KO mice. Conclusion We have generated and characterized the humanized dyslipidemic TKO-LDLR KO mouse. This mouse model presents human B and T cells and represents and important toll to investigate the impact of human adaptive immune cell pharmacological modulation in the context of atherosclerosis.

Identification of 1,3,4-Thiadiazolyl-Containing Thiazolidine-2,4-dione Derivatives as Novel PTP1B Inhibitors with Antidiabetic Activity.

Forty-one 1,3,4-thiadiazolyl-containing thiazolidine-2,4-dione derivatives (MY1-41) were designed and synthesized as protein tyrosine phosphatase 1B (PTP1B) inhibitors with activity against diabetes mellitus (DM). All synthesized compounds (MY1-41) presented potential PTP1B inhibitory activities, with half-maximal inhibitory concentration (IC50) values ranging from 0.41 ± 0.05 to 4.68 ± 0.61 μM, compared with that of the positive control lithocholic acid (IC50 = 9.62 ± 0.14 μM). The most potent compound, MY17 (IC50 = 0.41 ± 0.05 μM), was a reversible, noncompetitive inhibitor of PTP1B. Circular dichroism spectroscopy and molecular docking were employed to analyze the binding interaction between MY17 and PTP1B. In HepG2 cells, MY17 treatment could alleviate palmitic acid (PA)-induced insulin resistance by upregulating the expression of phosphorylated insulin receptor substrate and protein kinase B. In vivo, oral administration of MY17 could reduce the fasting blood glucose level and improve glucose tolerance and dyslipidemia in mice suffering from DM.

Abstract 2054: Adoptive Transfer Of Human Cd34+ Cells Promote Atherosclerosis In Rag2-ko/il2rg-ko/cd47-ko Immunocompromised Mice Independently Of Hypercholesterolaemia

Background and aim: Adaptive immune cells are involved in the development of atherosclerosis. Here we provide the immunemetabolic profile of an atheroprone immunodeficient mouse humanized with hCD34+ cells. Methods: LDLR-KO mice were crossed with the immunodeficient Rag2-KO/IL2rg-KO/CD47-KO (TKO, IMSR_JAX:025730) mouse model to generate an immunocompromised dyslipidemic mouse (TKO-LDLR KO mice). These mice present an intact innate immune system but lack B and T lymphocytes as well as NK cells. New born mice (within three days) were sub lethally irradiated (200 cGy) and received 2 x 10^5 hCD34+ cells. Results: when fed a cholesterol rich diet, non humanized TKO-LDLR KO present monocytosis with increased levels of Ly6Chi monocytes compared to TKO-LDLR KO at standard diet. Moreover, they develop marked dyslipidemia (plasma chol levels &gt;1200mg/dL), liver steatosis and moderate atherosclerosis at the aortic arch. The engraftment of human leukocytes (hCD45+) in the humanized group was evaluated after two months by flow cytometry analysis. Within the totality of circulating CD45+ cells, 10 to 30% were hCD45+, mainly B and T cells. Of note the presence of human lymphocytes was associated with a dramatic worsening of atherosclerosis as compared to non-humanized TKO-LDLR KO mice which was independent of plasma cholesterol levels which remained ex. Conclusion: Adoptive transfer of human CD34+ cells in dyslipidemic Rag2-KO/IL2rg-KO/CD47-KO immunocompromised mice promotes atherosclerosis independently of hypercholesterolemia, by affecting the maturation and distribution of the different B and T lymphocyte subsets.

Long-term Bisphenol S exposure induced gut microbiota dysbiosis, obesity, hepatic lipid accumulation, intestinal lesions and dyslipidemia in mice

Bisphenol S (BPS) is a commonly detected chemical raw material in water, which poses significant threats to both the ecological environment and human health. Despite being recognized as a typical endocrine disruptor and a substitute for Bisphenol A, the toxicological effects of BPS remain nonnegligible. In order to comprehensively understand the health impacts of BPS, a long-term (154 days) exposure experiment was conducted on mice, during which the physiological indicators of the liver, intestine, and blood were observed. The findings revealed that exposure to BPS resulted in dysbiosis of the gut microbiota, obesity, hepatic lipid accumulation, intestinal lesions, and dyslipidemia. Furthermore, there exists a significant correlation between gut microbiota and indicators of host health. Consequently, the identification of specific gut microbiota can be considered as potential biomarkers for the evaluation of risk associated with BPS. This study will effectively address the deficiency in toxicological data pertaining to BPS. The novel BPS data obtained from this research can serve as a valuable reference for professionals in the field.

Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon-like peptide 1.

Sotagliflozin is the first dual SGLT1/2 inhibitor antidiabetic drug approved by the US Food and Drug Administration for the management of heart failure. SGLT1/2 inhibition is observed to potentiate the secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1). The current preclinical research sought to investigate the effect of sotagliflozin on the secretion of fat-regulating peptides such as GLP-1, glucagon and fibroblast growth factor 21 (FGF21) and their prospective association with sotagliflozin's potential beneficial effects on dyslipidaemia. During an oral fat tolerance test in mice, sotagliflozin substantially increased GLP-1 and insulin concentrations. Although sotagliflozin alone did not ameliorate postprandial lipemia, its combination with linagliptin (DPP-IV inhibitor) significantly improved lipid tolerance comparable to orlistat (lipase inhibitor). In a triton-induced hypertriglyceridemia model, sotagliflozin, along with other medications (fenofibrate, exenatide and linagliptin) reduced fat excursion; however, co-administration with linagliptin provided no extra advantage. Furthermore, sotagliflozin stimulated glucagon secretion in the alpha TC1.6 cells and healthy mice, which resulted in an increased circulating FGF21 and β-hydroxybutyrate concentration. Finally, chronic treatment of sotagliflozin in high-fat diet (HFD)-fed obese mice resulted in reduced body weight gain, liver triglyceride, cholesterol, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) levels compared with the placebo group. However, the addition of linagliptin did not provide any additional benefit. In conclusion, sotagliflozin was found to have an effect on GLP-1 and also stimulate the release of glucagon and FGF21, which are important for regulating fat metabolism. Therefore, sotagliflozin might represent a potential therapeutic approach for the treatment of diabetic dyslipidemia and steatohepatitis.

Moderate-intensity continuous training reduces triglyceridemia and improves oxygen consumption in dyslipidemic apoCIII transgenic mice.

This study aimed to investigate metabolism modulation and dyslipidemia in genetic dyslipidemic mice through physical exercise. Thirty-four male C57Bl/6 mice aged 15 months were divided into non-transgenic (NTG) and transgenic overexpressing apoCIII (CIII) groups. After treadmill adaptation, the trained groups (NTG Ex and CIII Ex) underwent an effort test to determine running performance and assess oxygen consumption (V̇O2), before and after the training protocol. The exercised groups went through an 8-week moderate-intensity continuous training (MICT) program, consisting of 40 min of treadmill running at 60% of the peak velocity achieved in the test, three times per week. At the end of the training, animals were euthanized, and tissue samples were collected for ex vivo analysis. ApoCIII overexpression led to hypertriglyceridemia (P<0.0001) and higher concentrations of total plasma cholesterol (P<0.05), low-density lipoprotein (LDL) cholesterol (P<0.01), and very low-density lipoprotein (VLDL) cholesterol (P<0.0001) in the animals. Furthermore, the transgenic mice exhibited increased adipose mass (P<0.05) and higher V̇O2peak compared to their NTG controls (P<0.0001). Following the exercise protocol, MICT decreased triglyceridemia and cholesterol levels in dyslipidemic animals (P<0.05), and reduced adipocyte size (P<0.05), increased muscular glycogen (P<0.001), and improved V̇O2 in all trained animals (P<0.0001). These findings contribute to our understanding of the effects of moderate and continuous exercise training, a feasible non-pharmacological intervention, on the metabolic profile of genetically dyslipidemic subjects.

Walnut peptide alleviates obesity, inflammation and dyslipidemia in mice fed a high-fat diet by modulating the intestinal flora and metabolites.

Obesity is a chronic disease in which the body stores excess energy in the form of fat, and intestinal bacterial metabolism and inflammatory host phenotypes influence the development of obesity. Walnut peptide (WP) is a small molecule biopeptide, and the mechanism of action of WP against metabolic disorders has not been fully elucidated. In this study, we explored the potential intervention mechanism of WP on high-fat diet (HFD)-induced obesity through bioinformatics combined with animal experiments. PPI networks of Amino acids and their metabolites in WP (AMWP) and "obesity" and "inflammation" diseases were searched and constructed by using the database, and their core targets were enriched and analyzed. Subsequently, Cytoscape software was used to construct the network diagram of the AMWP-core target-KEGG pathway and analyze the topological parameters. MOE2019.0102 was used to verify the molecular docking of core AMWP and core target. Subsequently, an obese Mice model induced by an HFD was established, and the effects of WP on obesity were verified by observing weight changes, glucose, and lipid metabolism levels, liver pathological changes, the size of adipocytes in groin adipose tissue, inflammatory infiltration of colon tissue, and intestinal microorganisms and their metabolites. The network pharmacology and molecular docking showed that glutathione oxide may be the main active component of AMWP, and its main targets may be EGFR, NOS3, MMP2, PLG, PTGS2, AR. Animal experiments showed that WP could reduce weight gain and improve glucose-lipid metabolism in HFD-induced obesity model mice, attenuate hepatic lesions reduce the size of adipocytes in inguinal adipose tissue, and reduce the inflammatory infiltration in colonic tissue. In addition, the abundance and diversity of intestinal flora were remodeled, reducing the phylum Firmicutes/Bacteroidetes (F/B) ratio, while the intestinal mucosal barrier was repaired, altering the content of short-chain fatty acids (SCFAs), and alleviating intestinal inflammation in HFD-fed mice. These results suggest that WP intervenes in HFD-induced obesity and dyslipidemia by repairing the intestinal microenvironment, regulating flora metabolism and anti-inflammation. Our findings suggest that WP intervenes in HFD-induced obesity and dyslipidemia by repairing the intestinal microenvironment, regulating flora metabolism, and exerting anti-inflammatory effects. Thus, WP may be a potential therapeutic strategy for preventing and treating metabolic diseases, and for alleviating the intestinal flora disorders induced by these diseases. This provides valuable insights for the development of WP therapies.

Immune system humanization in dyslipidemic Rag2-KO/IL2rg-KO/CD47-KO/LDL-R KO mice controls atherosclerosis

Abstract Background and aim Given the key role of the immune response during atherosclerosis and the therapeutic interest of biologics targeting human immune cells, the need of experimental models to translate molecular mechanisms and to test therapeutic approaches for atherosclerosis is continuously increasing. Here we describe the characteristics of an innovative immunodeficient mouse humanized with hCD34+ cells on an atheroprone background. Methods LDLR-KO mice were crossed with the immunodeficient C57BL/6J strain Rag2-KO/IL2rg-KO/CD47-KO (TKO, IMSR_JAX:025730) to generate an immunocompromised dyslipidemic mouse recipient TKO-LDLR KO of human hematopoietic stem cells (hCD34+). Results TKO-LDLR KO were first characterized for their immune and metabolic profile. TKO mice are deficient in mature lymphocytes and NK cells and this profile was conserved in TKO-LDLR KO mice. Under high cholesterol diet for 8 weeks, both male and females TKO-LDLR KO present monocytosis with increased levels of Ly6Chi monocytes compared to TKO-LDLR KO at standard diet, develop marked dyslipidemia (total cholesterol 870.9 and 890.1 mg/dL male and females respectively), steatosis and atherosclerosis. This profile confirms the suitability of TKO-LDLR KO mice for atherosclerosis studies. Next we tested the impact of immune system humanization on atherosclerosis. TKO-LDLR KO pups received a low-dose irradiation (150-200 cGy) and thereafter 1,5-2 x 10^5 hCD34+ were injected with in the liver. Engraftment of human leukocytes (hCD45+) was evaluated after two months by flow cytometry analysis from tail blood. This approach allows to reconstitute between 10-30% of hCD45+, mainly B and T cells. The humanization with hCD34+ cells affected atherosclerosis development as compared to non-humanized TKO-LDLR KO mice. Conclusion We have generated and characterized for the first time a humanized dyslipidemic TKO-LDLR KO mice. This mouse model presents human B and T cells and represent and important toll to investigate the impact of biologics targeted toward human targets in the context of atherosclerosis.

(m-CF3-PhSe)2 counteracts metabolic disturbances and hypothalamic inflammation in a lifestyle rodent model.

An unhealthy lifestyle is associated with metabolic disorders and neuroinflammation. In this study, the efficacy of m-trifluoromethyl-diphenyl diselenide [(m-CF3-PhSe)2] against lifestyle model-related metabolic disturbances and hypothalamic inflammation in young mice was investigated. From postnatal day 25 (PND25) to 66, male Swiss mice were subjected to a lifestyle model, an energy-dense diet (20:20% lard: corn syrup) and sporadic ethanol (3x/week). Ethanol was administrated intragastrically (i.g., 2g/kg) to mice from PND45 to 60. From PND60 to 66, mice received (m-CF3-PhSe)2 (5mg/kg/day; i. g). (m-CF3-PhSe)2 reduced relative abdominal adipose tissue weight, hyperglycemia, and dyslipidemia in mice exposed to the lifestyle-induced model. (m-CF3-PhSe)2 normalized hepatic cholesterol and triglyceride levels, and the activity of G-6-Pase increased in lifestyle-exposed mice. (m-CF3-PhSe)2 was effective in modulating hepatic glycogen levels, citrate synthase and hexokinase activities, protein levels of GLUT-2, p-IRS/IRS, p-AKT/AKT, redox homeostasis, and inflammatory profile of mice exposed to a lifestyle model. (m-CF3-PhSe)2 counteracted hypothalamic inflammation and the ghrelin receptor levels in mice exposed to the lifestyle model. (m-CF3-PhSe)2 reversed the decreased levels of GLUT-3, p-IRS/IRS, and the leptin receptor in the hypothalamus of lifestyle-exposed mice. In conclusion, (m-CF3-PhSe)2 counteracted metabolic disturbances and hypothalamic inflammation in young mice exposed to a lifestyle model.

Impact of immune system humanization on atherosclerosis in dyslipidemic Rag2-KO/IL2rg-KO/CD47-KO/LDL-R KO mice

Aim: Given the key role of the immune response during atherosclerosis and the therapeutic interest of biologics targeting human immune cells, the need of experimental models to translate molecular mechanisms and to test therapeutic approaches for atherosclerosis is continuously increasing. Here we describe the characteristics of an innovative immunodeficient mouse humanized with hCD34+ cells on an atheroprone background. Methods: LDLR-KO mice were crossed with the immunodeficient C57BL/6J strain Rag2-KO/IL2rg-KO/CD47-KO (TKO, IMSR_JAX:025730) to generate an immunocompromised dyslipidemic mouse TKO-LDLR KO recipient of human hematopoietic stem cells (hCD34+). Results: TKO-LDLR KO were first characterized for their immune and metabolic profile. TKO mice are deficient in mature lymphocytes and NK cells and this profile was conserved in TKO-LDLR KO mice. Under high cholesterol diet for 8 weeks, both males and females TKO-LDLR KO present monocytosis with increased levels of Ly6Chi monocytes compared to TKO-LDLR KO at standard diet, develop marked dyslipidemia (total cholesterol 870.9 and 890.1 mg/dL male and females respectively), steatosis and atherosclerosis. This profile confirms the suitability of TKO-LDLR KO mice for atherosclerosis studies. Next, we tested the impact of immune system humanization. TKO-LDLR KO pups received a low-dose irradiation (150-200 cGy) and thereafter 1,5-2 x 10^5 hCD34+ were injected with in the liver. Engraftment of human leukocytes (hCD45+) was evaluated after two months by flow cytometry analysis from tail blood. This approach allows to reconstitute between 10-30% of hCD45+, mainly B and T cells. Conclusions: We have generated and characterized for the first time a humanized dyslipidemic TKO-LDLR KO mouse. This mouse model presents human B and T cells and could represent an important tool to investigate the impact of biologics targeted toward human targets in the context of atherosclerosis.

Clonal Blumea lacera (Burm. f.) DC. ameliorates diabetic conditions by modulating carbohydrate and lipid hydrolases: a combine in vivo experimental and chemico-biological interaction study.

Blumealacera(Burm. f.) DC. isanaromaticannual herbthat has traditionally beenused to treat or protect against diabetes. Although it has infallible uses, its supply is limited due to its short lifespan. In this study, we aim to investigate the anti-diabetic potential of its micropropagated plants in type 2 diabetic mammalian (mouse) model and further expand the molecular mechanistic understanding of its activity. The water extract of the micropropagated plants was tested in mice with streptozotocin-induced diabetes. The extract effectively suppressed glucose levels prevented weight loss, and improved dyslipidemia in mice. Additionally, it improved liver injury as well as all investigated toxicity indicators, including serum glutamate-pyruvate transaminase, serum glutamic oxaloacetic transaminase, and serum anti-inflammatory marker C-reactive protein. The intramolecular interaction study revealed that the innate polyphenolic constituents of this plant more profoundly inhibited α-amylase, α-glucosidase, and lipase compared to the standard. The prolific bioactive compounds of the micropropagated plant could be attributed to these superior anti-diabetic effects, presumably via an elaborate inhibition of carbohydrate and lipid hydrolyzing enzymes. Thus, the obtained results provide solid experimental proof of the year-round utility of micropropagated plants as a standard source plant material of Blumea lacera (Burm. f.) DC. for drug research and therapeutic production.

Proof-of-concept study for liver-directed miQURE technology in a dyslipidemic mouse model

A gene-silencing platform (miQURE) has been developed and successfully used to deliver therapeutic microRNA (miRNA) to the brain, reducing levels of neurodegenerative disease-causing proteins/RNAs via RNA interference and improving the disease phenotype in animal models. This study evaluates the use of miQURE technology to deliver therapeutic miRNA for liver-specific indications. Angiopoietin-like 3 (ANGPTL3) was selected as the target mRNA because it is produced in the liver and because loss-of-function ANGPTL3 mutations and/or pharmacological inhibition of ANGPTL3 protein lowers lipid levels and reduces cardiovascular risk. Overall, 14 candidate miRNA constructs were tested invitro, the most potent of which (miAngE) was further evaluated in mice. rAAV5-miAngE led to dose-dependent (≤-77%) decreases in Angptl3 mRNA in WT mice with ≤-90% reductions in plasma ANGPTL3 protein. In dyslipidemic APOE∗3-Leiden.CETP mice, AAV5-miAngE significantly reduced cholesterol and triglyceride levelsvs. vehicle and scrambled (miSCR) controls when administrated alone, with greater reductions when co-administered with lipid-lowering therapy (atorvastatin). A significant decrease in total atherosclerotic lesion area (-58% vs. miSCR) was observed in AAV5-miAngE-treated dyslipidemic mice, which corresponded with the maintenance of a non-diseased plaque phenotype and reduced lesion severity. These results support the development of this technology for liver-directed indications.

T-cell deficiency induces deficits in social behavior and dyslipidemia in mice.

Patients with neuropsychiatric disorders often exhibit an altered metabolic status. However, the underlying factors that induce behavioral and metabolic dysfunctions remain poorly understood. Therefore, we investigated whether behavioral and metabolic alterations could be induced in immunodeficient conditions. We found that T-cell-deficient Cd3e-/- mice exhibit deficits in social behavior associated with dyslipidemia. Cd3e-/- mice exhibited abnormal social novelty preference, but normal anxiety-like behavior. We also detected decreases in the concentrations of plasma triglyceride and the lipid transporter molecule fatty acid-binding protein 2. Furthermore, the adoptive transfer of T-cells to Cd3e-/- mice ameliorated the deficits in social behavior and recovered plasma triglyceride concentration. Thus, we found that T-cell disruption can induce defects in social behavior and systemic lipid homeostasis in mice. Given these findings, we believe that Cd3e-/- mice represent a useful tool for investigating the mechanisms of causal relationships among immune dysfunction, behavior, and metabolism.

ASTAXANTHIN PREVENTS HEPATOSTEATOSIS AND HYPERLIPIDEMIA BUT NOT OBESITY IN HIGH-FAT DIET FED MICE

Astaxanthin (AX) is a natural compound that regulates lipid metabolism in the liver, specifically in reducing hepatosteatosis. To the increment in Non-Alcoholic Fatty Liver Diseases (NAFLD) ratio and its burdens, prevention/treatment should address the world health problem. This study aimed to evaluate the ability of AX and its prolonged effects on the physiology of mice fed a high-fat diet. Mice fed with a high-fat diet (HFD) (n=12) were orally given AX at a dosage of 30 mg/kg body weight/day for 16 weeks, followed by eight weeks of AX termination, along with other CTL (normal chow diet) and HFD only group. At four time points of 8, 12, 16, and 24 weeks of the trial, three mice from each group were randomly dissected to collect blood, liver, and adipose tissue samples. AX given through oral gavage showed an excellent factor for maintaining total cholesterol, triglyceride, glucose, and Low-density Lipoprotein cholesterol (LDL-c). Moreover, AX did have impacts on preventing dyslipidemia in mice fed with HFD. Unexpectedly, AX supplied group caused excess weight gain in mice, shown in higher average body weight than HFD fed group. However, all the AX effects wore off after 8 weeks of termination. AX was a good player for liver and plasma lipid homeostasis, but not for weight control. Taken together, AX was a potential compound for preventing hepatosteatosis and hyperlipidemia, but not for controlling weight in mice fed with a HFD.