Figure 8.

Role of key regulating genes involved in hepatic and intestinal cholesterol metabolism. (A): SREBP2 is a major transcription factor regulating intracellular cholesterol homeostasis. It activates the transcription of LDLR, HMGCR and PCSK9 to control cholesterol uptake by LDLR in a self-regulating circuit. CYP7a1 catalyzes the rate limiting step of hepatic bile acid synthesis. FXR, which is primarily activated by bile acids, regulates bile acid synthesis by CYP7a1 via a negative feedback loop. (B): NPC1L1 is the major transporter protein for intestinal cholesterol absorption. To a lesser extent, SRBI is also involved in cholesterol absorption and secretion into lymph. Free cholesterol is esterified by ACAT2 for further processing into chylomicrons. Excessive free cholesterol is secreted back into the intestinal lumen by ABCG5. ABCA1 mediates the efflux of cholesterol directly into the blood stream. ASBT is the major transporter protein for reabsorption of bile acids within the enterohepatic circulation. Green arrows indicate changes (dark green represents significant changes, bright green represents trends) in CONV HFD+Ator mice compared to CONV HFD mice. The red arrows indicate changes (dark red represents significant changes, bright red represents trends) in ABS HFD+Ator compared to ABS HFD mice.