Intestinal lymphatic HDL miR-223 and ApoA-I are reduced during insulin resistance and restored with niacin

Rabban Mangat, Faye Borthwick, Tina Haase, Miriam Jacome, Randy Nelson, Anatol Kontush, Donna F. Vine, Spencer D. Proctor

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The intestine is involved in whole-body lipid and cholesterol homeostasis and secretes lipoproteins containing apolipoprotein(Apo)B48 anddiscreteApoA-I into themesenteric lymph.Thelymphatic systemhasbeen proposed to have a significant role in the reverse cholesterol transport pathway associated with HDL-ApoA-I. In conditions of insulin resistance (IR), there is intestinal overproduction of chylomicrons containing ApoB48; however, there is limited data on the intestinal synthesis and secretion of HDL-ApoA-I.microRNA (miR)-223 has been shown to regulate peripheral HDL metabolism and may impact intestinal-derived HDL. Niacin (nicotinic acid; vitamin B3) is known to regulate lipid metabolism, but the role of niacin in modulating intestinal lipid and lipoprotein (ApoB48 and ApoA-I) metabolism is unknown. The aimof this study was to determine the secretion of intestinal lymphatic HDL-ApoA-I and the effect of dietary intervention with niacin on these pathways in a rodent model of IR. HDL was isolated from intestinal mesenteric lymph by density ultracentrifugation, and subsequent HDLmiRanalysiswas developed in collaboration with Exiqon Services. Insulin-resistant rodentswere fed chowor chowwithniacin (1%w/w) for 6wk. Intestinal lymphHDL-ApoA-I andmiR-223 expressionwere lowerbyat least 45 and 60%, respectively, and lymphHDLwas associatedwith 85%higher triglyceride (TG) content in IR compared to non-IR control group.Niacin was found to increase secretion of lymphHDL andmiR-223 by at least 50-60%and to deplete the TGs associated with HDL compared with the nontreated IR group. Niacin significantly increased peroxisome proliferator-activating nuclear receptor α and carnitine palmitoyltransferase I α mRNA and annulled Tnf-α mRNA expression in intestinal (jejunal) explants. Altered intestinal lymphatic HDL-ApoA-I and miR-223 metabolism in IR and modulation by niacin may provide insight into the intestinal-mediated regulation of the reverse cholesterol transport pathway.

Original languageEnglish
Pages (from-to)1602-1612
Number of pages11
JournalFASEB Journal
Volume32
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • ApoB48
  • Chylomicrons
  • Lipid metabolism
  • Lipoproteins
  • Niacin/nicotinic acid

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