Description

• A cell-permeable pentacyclic triterpenoid from birch bark extract that interacts with SCAP (SREBP cleavage activating protein) and prevents SREBP (sterol regulatory element-binding protein) Golgi proteolytic activation (1 to 13.55μM in Rat hepatocytes CRL-1601) via a similar mechanism as oxysterols by inducing the association of SCAP with Insig-1 (insulin-induced gene-1), thereby causing SCAP-SREBPs complex ER retention
• Unlike oxysterols, Betulin does not activate LXR to induce concomitant HMGCR (HMG-CoA reductase) degradation and SREBP-1 up-regulation
• While both Betulin and HMGCR inhibitor Lovastatin (Cat
• No
• 438185) inhibit cellular cholesterol synthesis (by ∽70% in CRL-1601 cultures with respective compound at 13.55 and 1μM concentration), only Betulin suppresses cellular fatty acid synthesis (by ∽55% at 13.55μM in CRL-1601)
• Betulin is shown to exhibit comparable in vivo efficacy as Lovastatin (both dosed at 30mg/kg/day with chow) in ameliorating high fat/cholesterol diet-induced obesity (% fat/lean tissue ratio increase from non-fat diet mice = 167, 44, and 33 in mice consuming fat diet alone, with Lovastatin, with Betulin, respectively)
• However, only Betulin is demonstrated to lower fasting blood glucose and insulin levels and reduce fat cell size in white adipose tissue in high fat diet mice
• Fatostatin (Cat
• No
• 341329) in comparison does not target SCAP via sterol-binding site, nor does it induce SCAP binding to Insig-1.