Knockdown of ORP6 in THP-1 macrophages upregulates mRNA of SREBF2
and genes induced by SREBF1/2, HMGCR, and LDLR.
A greater function of SREBF2 than SREBF1 in milk fat synthesis has been hypothesized .
Network analysis shows that FASN, SREBF1, SREBF2, PPARG, and ACSS2 are the major components of the milk fat synthesis pathway.
Finally, the mRNA levels encoded by the genes for the low-density-lipoprotein receptor (LDLR), the sterol-regulatory-element-binding transcription factor (SREBF2), the very-low-density-lipoprotein receptor (VLDLR), and the acetyl-CoA carboxylase (ACACA) were determined by real-time RT-PCR.
G also enhanced the mRNAs encoding the LDL and VLDL receptors and reduced ACACA mRNA, without altering the transcription of the mRNA encoding the SREBF2. Conclusions: The following mechanisms may have mediated the decrease in plasma lipids levels in mice: a down-regulation of hepatocyte-cholesterol synthesis occurred as a result of decreased HMGCR protein levels and catalytic activity; the levels of LDLR mRNA became elevated, thus suggesting an increase in the uptake of serum LDL, especially by the liver; and TG synthesis became reduced very likely because of a decrease in fatty-acid synthesis.
Recently, microRNA-33a and -b (miR-33a/b), intronic miRNAs located within the SREBF2 and SREBF1, respectively, have been revealed to suppress expression of the cholesterol transporter ABC transporter A1 (ABCA1), a key regulator of HDL synthesis [5, 6].
It has been reported that , in mouse peritoneal macrophages, depletion of cholesterol with simvastatin showed robust upregulation of both miR-33 and SREBF2.
A, polypeptide 11 Triacylglycerol synthesis AGPAT6 1-Acylglycerol-3-phosphate MAC-T [??]PPAR[gamma] O-acyltransferase 6 DGAT1 Diacylglycerol O- MAC-T [??]PPAR[gamma] acyltransferase 1 LPIN1 Lipin 1 MAC-T [??]PPAR[gamma] MDBK [??]PPAR[alpha] LPIN3 Lipin 3 MDBK [??]PPAR[alpha] Cholesterol synthesis HMGCR 3-Hydroxy-3- MDBK [??]PPAR[alpha] methylglutaryl-CoA reductase SREBF2
Sterol regulatory element MAC-T [??]PPAR[gamma] binding transcription factor 2 Signaling molecules ANGPTL4 Angiopoietin-like 4 Liver [??]PPAR[alpha] MDBK [??]PPAR[alpha] FGF21 Fibroblast growth factor Liver [??]PPAR[alpha] 21 EDN1 Endothelin 1 BAEC [??]PPAR[alpha] [??]PPAR[gamma] LEP Leptin bS.
However compared with WC group, EC group showed significantly higher mRNA expression of ACC (encoded by gene Acaca) (P = 0.007), SREBP-1c (encoded by gene Srebf1) (P < 0.001), and SREBP-2 (encoded by gene Srebf2
) (P = 0.048) (Figures 1 and 3), while there was no significant difference in TFL or TCL group for all these gene expressions compared with WC group.
The researchers uncovered three novel signals, from the genes TOMM40-APOE-APOC1, SREBF2
and NTRK2) that were significantly associated with BMI in adults.
Structure of the Human Gene Encoding Sterol Regulatory Element Binding Protein 2 (SREBF2
Enzyme-linked immunosorbent assay (ELISA)