Details

Autor(en) / Beteiligte

• Milligan, Sherrelle
• Martin, Gregory G.
• Landrock, Danilo
• McIntosh, Avery L.
• Mackie, John T.
• Schroeder, Friedhelm
• Kier, Ann B.

Titel

Ablating both Fabp1 and Scp2/Scpx (TKO) induces hepatic phospholipid and cholesterol accumulation in high fat-fed mice

Ist Teil von

• Biochimica et biophysica acta. Molecular and cell biology of lipids, 2018-03, Vol.1863 (3), p.323-338

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Although singly ablating Fabp1 or Scp2/Scpx genes may exacerbate the impact of high fat diet (HFD) on whole body phenotype and non-alcoholic fatty liver disease (NAFLD), concomitant upregulation of the non-ablated gene, preference for ad libitum fed HFD, and sex differences complicate interpretation. Therefore, these issues were addressed in male and female mice ablated in both genes (Fabp1/Scp2/Scpx null or TKO) and pair-fed HFD. Wild-type (WT) males gained more body weight as fat tissue mass (FTM) and exhibited higher hepatic lipid accumulation than WT females. The greater hepatic lipid accumulation in WT males was associated with higher hepatic expression of enzymes in glyceride synthesis, higher hepatic bile acids, and upregulation of transporters involved in hepatic reuptake of serum bile acids. While TKO had little effect on whole body phenotype and hepatic bile acid accumulation in either sex, TKO increased hepatic accumulation of lipids in both, specifically phospholipid and cholesteryl esters in males and females and free cholesterol in females. TKO-induced increases in glycerides were attributed not only to complete loss of FABP1, SCP2 and SCPx, but also in part to sex-dependent upregulation of hepatic lipogenic enzymes. These data with WT and TKO mice pair-fed HFD indicate that: i) Sex significantly impacted the ability of HFD to increase body weight, induce hepatic lipid accumulation and increase hepatic bile acids; and ii) TKO exacerbated the HFD ability to induce hepatic lipid accumulation, regardless of sex, but did not significantly alter whole body phenotype in either sex. •Ablating Fabp1 or Scp2 may exacerbate ad lib fed high-fat diet (HFD) induced NAFLD.•Confounded by upregulated non-ablated gene, preference for HFD, and sex difference•Pair-fed HFD differentially impacts body weight and hepatic lipid in male vs female.•Ablating both genes (TKO) exacerbates hepatic lipid, but not weight gain in either sex.•TKO selectively increased liver phospholipid & cholesteryl ester, but not triglyceride.