Changes in liver perilipin gene expression during an oral lipid load in obese OLETF rats

Abstract

Non‐alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver maladies in the US. NAFLD is associated with obesity, hyperlipidemia, hypertension, insulin resistance, and diabetes; all traits linked to metabolic syndrome, affecting 20% of the US population. Inappropriate hepatic lipid accumulation is associated with metabolic syndrome. Intracellular lipid storage is regulated by lipid droplets (LDs) that are active components of the cell. LDs have surface proteins of which the most studied belong to the PAT family (Perilipin1–5), which participate in storage and lipid metabolism. To evaluate the effect that a high‐lipid load on the expression and dynamics of hepatic perilipins during early onset T2D, an oral fat tolerance test (OFTT) was performed in 28 wk‐old rats (n=5–6/group): (1) healthy, strain control LETO, and (2) obese, diabetic OLETF. Liver and blood were collected before (T0) and after (T1, T2, T4, and T8 hours) the lipid challenge. An acute increase in serum TG was observed at T2 (p= < 0.0001) and was maintained over the next 6 hours in OLETF whereas in LETO it decreased after the T2 mark. The mRNA expression of Plin2 increased 2.5‐fold in OLETF at T2 compared to LETO, and increased 2.5‐fold at T8 in LETO compared to baseline. Plin3 remained higher (p= 0.0077) in LETO compared to OLETF at T8. Plin4 did not change significantly in response to the lipid challenge between groups. Plin5 increased 1.8‐fold in LETO at T8 compared to baseline. These changes help explain the contributions of LDs to the regulation of hepatic lipids during both normal and diabetic conditions in response to a high lipid challenge similar to the consumption of a high‐fat meal. As Plin2 and 3 have been described as structural LD‐associated proteins, being present mostly in nascent LD, suggesting that a high fat load induces an acute induction of hepatocyte lipid storage. The increase in Plin5 suggests that lipid metabolism pathways are being activated, as Plin5 has been related with mitochondrial FA metabolism. The differential expression patterns of perilipins in response to an acute lipid challenge illustrates the timing of the cellular changes during the development of hepatic steatosis, providing useful insights into future development of treatment by targeting the PAT family of proteins.Support or Funding InformationThis work was supported by NIH's MHRT program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.