Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice.

• Transcriptomics analysis revealed that genes involved in hepatic de novo cholesterol synthesis were downregulated in fed HSL-null mice that had been on a high-fat diet (HFD) for 6 mo. This finding prompted a further analysis of cholesterol metabolism in HSL-null mice, which was performed in fed and 16-h-fasted mice on a normal chow diet (ND) or HFD regimen. Plasma cholesterol was elevated in HSL-null mice, in all tested conditions, as a result of cholesterol enrichment of HDL and VLDL. Hepatic esterified cholesterol content and ATP-binding cassette transporter A1 (ABCA1) mRNA and protein levels were increased in HSL-null mice regardless of the dietary regimen. Unsaturated fatty acid composition of hepatic triglycerides was modified in fasted HSL-null mice on ND and HFD. The increased ABCA1 expression had no major effect on cholesterol efflux from HSL-null mouse hepatocytes. Taken together, the results of this study suggest that HSL plays a critical role in the hydrolysis of cytosolic cholesteryl esters and that increased levels of hepatic cholesteryl esters, due to lack of action of HSL in the liver, are the main mechanism underlying the imbalance in cholesterol metabolism in HSL-null mice.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

ATP-Binding Cassette Transporters

biosynthesis

genetics

Animals

Cholesterol

biosynthesis

metabolism

physiology

Cytosol

metabolism

Down-Regulation

physiology

Fatty Acids

metabolism

Hepatocytes

metabolism

Homeostasis

physiology

Hydroxymethylglutaryl-CoA Reductase Inhibitors

pharmacology

Lipids

blood

Lipoproteins

blood

Liver

metabolism

Mice

Mice

Knockout

Oligonucleotide Array Sequence Analysis

Reverse Transcriptase Polymerase Chain Reaction

Sterol Esterase

genetics

physiology

Triglycerides

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)