Egg yolk phosphatidylcholine is more effective than soybean phosphatidylcholine in improving dyslipidemia of obesity in mice fed a high-fat diet

This study aimed to evaluate the effects of dietary egg yolk phosphatidylcholine (EPC) and soybean phosphatidylcholine (SPC) on obesity mice fed a high-fat diet (HFD). After 60 days of dietary intervention, the effects were evaluated by biochemical indices and serum lipidomic analysis. EPC and SPC markedly reduced serum total cholesterol, serum triacylglycerol (TAG) and low-density lipoprotein cholesterol, while increased high-density lipoprotein cholesterol. EPC was more effective in reducing malondialdehyde and superoxide dismutase in liver than SPC. Main lipids including glycerophospholipids, TAG, sphingolipids and fatty acyls were significantly modified by EPC. Compared with HFD, EPC increased 10 main differential lipids such as phosphatidyl ethanolamine (22:6_20:0). The expressions of related protein including sterol-regulatory element binding proteins sterol-regulatory element binding proteins (SREBP-1c) and peroxisome proliferator-activated receptor α (PPAR-α) were significantly down-regulated with EPC treatment. Therefore, EPC was more effective than SPC in improving obesity by regulating glycerophospholipid metabolism.

The Hypolipidemic Effect of Dalbergia odorifera T. C. Chen Leaf Extract on Hyperlipidemic Rats and Its Mechanism Investigation Based on Network Pharmacology

Objective. The aim of this study was to explore the hypolipidemic effect and mechanism of Dalbergia odorifera T. C. Chen leaf extract. Methods. The hypolipidemic effect of D. odorifera leaf extract was investigated using a hyperlipidemic rat model. Then, its mechanism was predicted using network pharmacology methods and verified using western blotting. Results. Compared with the levels in the model group, the serum levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) decreased significantly, whereas the serum level of high-density lipoprotein cholesterol (HDL-C) increased dramatically after treatment with the extract. The degrees of hepatocyte steatosis and inflammatory infiltration were markedly attenuated in vivo. Then, its hyperlipidemic mechanism was predicted using network pharmacology-based analysis. Thirty-five key targets, including sterol regulatory element-binding protein cleavage-activating protein (SCAP), sterol regulatory element-binding protein-2 (SREBP-2), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), low-density lipoprotein receptor (LDLR), and ten signaling pathways, were associated with hyperlipidemia. Finally, it was verified that the extract downregulated the protein levels of SCAP, SREBP-2, and HMGCR, and upregulated protein levels of LDLR. Conclusion. These findings provided additional evidence of the hypolipidemic effect of D. odorifera leaf extract.

Increased Ratio of CD14++CD80+ Cells/CD14++CD163+ Cells in the Infrapatellar Fat Pad of End-Stage Arthropathy Patients

ObjectivesThis study sought to identify the ratio of M1/M2 cells in the infrapatellar fat pads (IFP) and subcutaneous fat tissues (SC) of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. The clinical features of OA and RA patients treated with or without biological disease-modifying anti-rheumatic drugs (bDMARDs) were also assessed.MethodsIFP and SC were collected from patients with OA and RA who are undergoing total knee arthroplasty (TKA). CD14-positive cells were then isolated from these samples. Flow cytometry was used to determine the number of CD14++CD80+ cells and CD14++CD163+ cells. The expression levels of lipid transcription factors, such as sterol regulatory element-binding protein 1 (SREBP1) and liver X receptor alpha (LXRA), and inflammatory cytokines were also evaluated.ResultsTwenty OA patients and 22 RA patients were enrolled in this study. Ten of the RA patients (45.4%) received bDAMRDs before TKA. On average, a fivefold increase in the number of CD14-positive cells and lower expression levels of SREBP1C and LXRA were observed in OA IFP relative to OA SC; however, these results were not obtained from the RA samples. The median ratio of CD14++CD80+ cells/CD14++CD163+ cells of OA IFP was 0.87 (0.76–1.09, interquartile range), which is higher to that of OA SC with a lower ratio (p = 0.05835).ConclusionsThe quantity and quality of CD14-positive cells differed between IFP and SC in arthropathy patients. To our knowledge, this is the first study to characterize the ratio of M1/M2 cells in the IFP and SC of end-stage OA and RA patients. The increased ratio of CD14++CD80+ cells/CD14++CD163+ cells in the IFP from patients with OA and RA treated with bDMARDs indicated that inflammation was localized in the IFP. As adipose tissue-derived innate immune cells were revealed as one of the targets for regulating inflammation, further analysis of these cells in the IFP may reveal new therapeutic strategies for inflammatory joint diseases.

The transcriptional corepressor CtBP2 serves as a metabolite sensor orchestrating hepatic glucose and lipid homeostasis

Biological systems to sense and respond to metabolic perturbations are critical for the maintenance of cellular homeostasis. Here we describe a hepatic system in this context orchestrated by the transcriptional corepressor C-terminal binding protein 2 (CtBP2) that harbors metabolite-sensing capabilities. The repressor activity of CtBP2 is reciprocally regulated by NADH and acyl-CoAs. CtBP2 represses Forkhead box O1 (FoxO1)-mediated hepatic gluconeogenesis directly as well as Sterol Regulatory Element-Binding Protein 1 (SREBP1)-mediated lipogenesis indirectly. The activity of CtBP2 is markedly defective in obese liver reflecting the metabolic perturbations. Thus, liver-specific CtBP2 deletion promotes hepatic gluconeogenesis and accelerates the progression of steatohepatitis. Conversely, activation of CtBP2 ameliorates diabetes and hepatic steatosis in obesity. The structure-function relationships revealed in this study identify a critical structural domain called Rossmann fold, a metabolite-sensing pocket, that is susceptible to metabolic liabilities and potentially targetable for developing therapeutic approaches.

The CCAAT-binding complex mediates azole susceptibility of Aspergillus fumigatus by suppressing SrbA expression and cleavage

In fungal pathogens, the transcription factor SrbA (a sterol regulatory element-binding protein, SREBP) and CBC (CCAAT binding complex) have been reported to regulate azole resistance by competitively binding the TR34 region (34 mer) in the promoter of the drug target gene, erg11A. However, current knowledge about how the SrbA and CBC coordinately mediate erg11A expression remains limited. In this study, we uncovered a novel relationship between HapB (a subunit of CBC) and SrbA in which deletion of hapB significantly prolongs the nuclear retention of SrbA by increasing its expression and cleavage under azole treatment conditions, thereby enhancing Erg11A expression for drug resistance. Furthermore, we verified that loss of HapB significantly induces the expression of the rhomboid protease RbdB, Dsc ubiquitin E3 ligase complex, and signal peptide peptidase SppA, which are required for the cleavage of SrbA, suggesting that HapB acts as a repressor for these genes which contribute to the activation of SrbA by proteolytic cleavage. Together, our study reveals that CBC functions not only to compete with SrbA for binding to erg11A promoter region but also to affect SrbA expression, cleavage, and translocation to nuclei for the function, which ultimately regulate Erg11A expression and azole resistance.

Polymorphism of Insulin-induced gene 1 (INSIG1) of three local beef cattle in Indonesia

Insulin-induced gene 1 (INSIG1) encoded protein that blocked of proteolysis activity from protein sterol regulatory element binding proteins (SREBP). The role gene plays of cholesterol, fatty acid, and glucose metabolism. Indonesia has many several beef cattle which has good quality of growth trait. The aim of this study was to identify polymorphism of INSIG1 gene (SNP 4366 (A>G) and 4534 (T>C)) of three local beef cattle in Indonesia (Bali, Pasundan and Ongole Decendent). One hundred and twenty seven samples were used in this study consisting of Bali cattle (46) from Pulukan Bali Island, Pasundan (36) from UPTD BPPT Beef cattle Ciamis West Java and Ongole Grade (OD) (45). DNA was extracted from whole blood using High Salt method then genotyping used PCR-RFLP method with RsaI and TaqI enzymes. Parameters in this study were genotype and allele frequencies, heterozigosity observed (Ho), expected (He), Hardy-Weinberg Equilibrium (HWE) and Polymorphism Information Content (PIC). Result showed that a 428 bp of DNA fragment was successfully amplified and digested. Three variant of genotypes with two alleles were identified. For SNP 4366 (A>G) were AA, AG and GG with dominant of G allele while SNP 4534 (T>C) were CC, CT and TT with dominant C allele. Both of SNPs in each of breed populations was in Hardy-Weinberg Equilibrium and polymorphic. Additionally, PIC value reached moderate. In conclusion, polymorphism was found in beef cattle and it could be early study for genetic diversity

miR-23a/b-3p promotes hepatic lipid accumulation by regulating Srebp-1c and Fas

miR-23a-3p and miR-23b-3p are members of the miR-23~27~24-2 superfamily. The role of miR-23a/b-3p in regulating hepatic lipid accumulation is still unknown. Here, we found that increased miR-23a-3p and miR-23b-3p levels were accompanied by an increase in the protein levels of the sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) in the steatotic livers of mice fed a high-fat diet (HFD) and leptin-receptor-deficient type 2 diabetic mice (db/db). Importantly, overexpression of miR-23a/b-3p in Hep1-6 cells elevated the intracellular triglyceride level and upregulated the expression of Srebp-1c and Fas. Taken together, these results suggested that miR-23a/b-3p enhanced mRNA stability by binding the 5'-UTR of Srebp-1c and Fas mRNA, thereby promoting triglyceride accumulation in hepatocytes.

The SREBP (Sterol Regulatory Element-Binding Protein) pathway: a regulatory bridge between carotenogenesis and sterol biosynthesis in the carotenogenic yeast Xanthophyllomyces dendrorhous

Xanthophyllomyces dendrorhous is a basidiomycete yeast that naturally produces the red–orange carotenoid astaxanthin, which has remarkable antioxidant properties. The biosynthesis of carotenoids and sterols share some common elements that have been studied in X. dendrorhous. For example, their synthesis requires metabolites derived from the mevalonate pathway and in both specific pathways, cytochrome P450 enzymes are involved that share a single cytochrome P450 reductase, CrtR, which is essential for astaxanthin biosynthesis, but is replaceable for ergosterol biosynthesis. Research on the regulation of carotenoid biosynthesis is still limited in X. dendrorhous; however, it is known that the Sterol Regulatory Element-Binding Protein (SREBP) pathway, which is a conserved regulatory pathway involved in the control of lipid metabolism, also regulates carotenoid production in X. dendrorhous. This review addresses the similarities and differences that have been observed between mammal and fungal SREBP pathways and what it is known about this pathway regarding the regulation of the production of carotenoids and sterols in X. dendrorhous.