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The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression.
It is reported that in glucogenetic kidney epithelial cells, Pepck and G6p expression are induced by dexamethasone and cAMP, but fail to be inhibited by insulin, consistent with the possibility that Foxo1 is involved in insulin regulation of glucose production by mediating the ability of insulin to decrease the glucocorticoid/cAMP response of G 6p.
Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid
This work identifies a member of the major facilitator superfamily—Mfsd2a (previously an orphan transporter)—as the major transporter for DHA uptake into brain and reveals an unexpected essential physiological role of plasma-derived LPCs in brain growth and function.
Specific Binding of ApoA-I, Enhanced Cholesterol Efflux, and Altered Plasma Membrane Morphology in Cells Expressing ABC1*
The studies provide evidence for a direct interaction between ABC1 and apoA-I, but not HDL, indicating that free apoB-I is the metabolic substrate for ABC1, while cells overexpressing ABC1 displayed a distinctive morphology, characterized by plasma membrane protrusions and resembling echinocytes that form when there are excess lipids in the outer membrane hemileaflet.
Evolutionarily conserved gene family important for fat storage
Identification of a conserved gene family important for lipid droplet formation named fat-inducing transcript (FIT) and depletion of FIT2 in zebrafish blocks diet-induced accumulation of lipid droplets in the intestine and liver, highlighting an important role for FIT 2 in lipid Droplet formation in vivo.
ATP-binding Cassette Transporter A1 (ABCA1) Functions as a Cholesterol Efflux Regulatory Protein*
The data suggest that the binding of apoA-I to ABCA1 leads to the formation of phospholipid-apoA- I complexes, which subsequently promote cholesterol efflux in an autocrine or paracrine fashion.
High Density Lipoprotein (HDL) Particle Uptake Mediated by Scavenger Receptor Class B Type 1 Results in Selective Sorting of HDL Cholesterol from Protein and Polarized Cholesterol Secretion*
  • D. Silver, Nan Wang, Xiao Xiao, A. Tall
  • Chemistry, Medicine
    The Journal of Biological Chemistry
  • 6 July 2001
High density lipoprotein particles, internalized via SR-BI, undergo a novel process of selective transcytosis, leading to polarized cholesterol transport, which is involved in uptake and degradation of apoE-free HDL in hepatocytes.
A PEST sequence in ABCA1 regulates degradation by calpain protease and stabilization of ABCA1 by apoA-I.
A novel mode of regulation of ABCA1 by PEST sequence-mediated calpain proteolysis that appears to be reversed by apolipoprotein-mediated phospholipid efflux is revealed and could represent a novel therapeutic approach to increasing macrophage cholesterol efflux and decreasing atherosclerosis.
Direct binding of triglyceride to fat storage-inducing transmembrane proteins 1 and 2 is important for lipid droplet formation
It is shown that FIT proteins purified in detergent micelles directly bind triolein with specificity and saturation-binding kinetics and implicates triglyceride binding as important for FIT-mediated LD formation.
Increased high density lipoprotein (HDL), defective hepatic catabolism of ApoA-I and ApoA-II, and decreased ApoA-I mRNA in ob/ob mice. Possible role of leptin in stimulation of HDL turnover.
The studies reveal a specific HDL particle catabolic pathway that is down-regulated in ob/ob mice and suggest that HDL apolipoprotein turnover may be regulated by obesity and/or leptin signaling.
The Scavenger Receptor Class B Type I Adaptor Protein PDZK1 Maintains Endothelial Monolayer Integrity
It is shown that the PDZ domain-containing protein PDZK1 is expressed in endothelium and required for HDL activation of endothelial NO synthase and cell migration; in contrast, endothelial cell responses to other stimuli, including vascular endothelial growth factor, are PDzK1-independent.