Crosstalk Between Dietary Fatty Acids and MicroRNAs in the Regulation of Hepatic ApoB-Containing Lipoprotein Synthesis in Humans

Abstract

Enhanced hepatic synthesis, assembly, and secretion of apolipoprotein B (ApoB)-containing lipoproteins elevate their plasma levels and-like their impaired clearance from the circulation-can increase cardiovascular risk. Both dietary fatty acids and microRNAs contribute to the nutrient-dependent regulation of hepatic gene expression. Together, these factors may modulate lipid and ApoB-containing lipoprotein synthesis in the liver, either exacerbating or mitigating dyslipidemia. Research continues to reveal the complexity of fatty acid-microRNA networks and highlights differences in regulating hepatic ApoB-containing lipoprotein synthesis between humans and rodents. Consequently, this review focuses on studies conducted in humans or human-derived hepatocytes.

Keywords: ApoB100; MUFA; PUFA; SFA; VLDL; dyslipidemia; human; miR; nutritional regulation.

Figure 1

Human microRNAs that regulate hepatic ApoB-containing lipoprotein synthesis and assembly. APOB, gene encoding apolipoprotein B; HNF4α, hepatocyte nuclear factor 4α; PPARγ, peroxisome proliferator-activated receptor γ; SREBP-1, sterol regulatory element-binding protein 1; SREBP-2, sterol regulatory element-binding protein 2; ACC, acetyl-CoA carboxylase; FAS, fatty acid synthase; SCD, stearoyl-CoA desaturase; CD36, fatty acid translocase; MTP, microsomal triglyceride transfer protein; VLDL, very low density lipoprotein.

Figure 2

Network of fatty acids and microRNAs modulating hepatic synthesis of lipids and ApoB-containing lipoproteins. ApoB100, apolipoprotein B100; HNF4α, hepatocyte nuclear factor 4α; MTP, microsomal triglyceride transfer protein; MUFAs, monounsaturated fatty acids; PUFAs, polyunsaturated fatty acids; SFAs, saturated fatty acids; VLDL, very low density lipoprotein; TG, triglyceride; LA, linoleic acid; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid.

Figure 3

Fatty acid-dependent regulation of TG synthesis and VLDL production by hepatic miR-130b through targeting PPARγ mRNA. PUFAs, polyunsaturated fatty acids; SFAs, saturated fatty acids; PPARγ, peroxisome proliferator-activated receptor γ; TG, triglyceride; VLDL, very low density lipoprotein.