PPARalpha activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes.

• Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that is expressed in various tissues. In mice treated with the peroxisome proliferator-activated receptor alpha (PPARalpha) agonist Wy14,643 (Wy), hepatic mRNA and protein levels of ADRP as well as hepatic triglyceride content increased. Also in primary mouse hepatocytes, Wy increased ADRP expression and intracellular triglyceride mass. The triglyceride mass increased in spite of unchanged triglyceride biosynthesis and increased palmitic acid oxidation. However, Wy incubation decreased the secretion of newly synthesized triglycerides, whereas apolipoprotein B secretion increased. Thus, decreased availability of triglycerides for VLDL assembly could help to explain the cellular accumulation of triglycerides after Wy treatment. We hypothesized that this effect could be mediated by increased ADRP expression. Similar to PPARalpha activation, adenovirus-mediated ADRP overexpression in mouse hepatocytes enhanced cellular triglyceride mass and decreased the secretion of newly synthesized triglycerides. In ADRP-overexpressing cells, Wy incubation resulted in a further decrease in triglyceride secretion. This effect of Wy was not attributable to decreased cellular triglycerides after increased fatty acid oxidation because the triglyceride mass in Wy-treated ADRP-overexpressing cells was unchanged. In summary, PPARalpha activation prevents the availability of triglycerides for VLDL assembly and increases hepatic triglyceride content in part by increasing the expression of ADRP.

Subject headings

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

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

Keyword

Acyl-CoA Dehydrogenase

Long-Chain

genetics

Acyl-CoA Oxidase

genetics

Animals

Apolipoprotein B-100

Apolipoprotein B-48

Apolipoproteins B

secretion

Carnitine O-Palmitoyltransferase

genetics

Dietary Fats

administration & dosage

pharmacology

Gene Expression

drug effects

genetics

Hepatocytes

drug effects

metabolism

secretion

Liver

drug effects

metabolism

Membrane Proteins

genetics

metabolism

Mice

Mice

Inbred C57BL

Mice

Knockout

Oxidation-Reduction

PPAR alpha

antagonists & inhibitors

genetics

metabolism

Palmitic Acid

metabolism

Peroxisome Proliferators

pharmacology

Pyrimidines

pharmacology

Transfection

Triglycerides

biosynthesis

metabolism

secretion

Publication and Content Type

ref (subject category)

art (subject category)