Reversal of diet-induced hepatic steatosis by peripheral CB1 receptor blockade in mice is p53/miRNA-22/SIRT1/PPARα dependent

Shahar Azar, Shiran Udi, Adi Drori, Rivka Hadar, Alina Nemirovski, Kiran V Vemuri, Maya Miller, Dana Sherill-Rofe, Yhara Arad, Devorah Gur-Wahnon, Xiaoling Li, Alexandros Makriyannis, Danny Ben-Zvi, Yuval Tabach, Iddo Z Ben-Dov, Joseph Tam. Mol Metab. 2020;42:101087.

Laboratory studyOther animalsWith AM6545 (a peripheral CB1 receptor blocker, tested alone)

This study tested palmitoylethanolamide together with AM6545 (a peripheral CB1 receptor blocker, tested alone). Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.

Design

Laboratory study

Subjects

Diet-induced obese mice, wild-type, PPAR-alpha knockout and liver SIRT1 knockout; plus hepatocyte cultures (numbers not stated in the abstract)

Dose used in the study

AM6545; dose and route not stated in the abstract

Duration

Not stated in the abstract

What was measured

Liver fat and injury, hepatic PPAR-alpha expression and activity, hepatic oleoylethanolamide and palmitoylethanolamide levels, SIRT1, p53 and microRNA-22, and phylogenetic profiling.

What the authors reported

Peripheral CB1 blockade reversed liver steatosis and improved liver injury in wild-type but not PPAR-alpha knockout mice. The effect went with higher hepatic PPAR-alpha activity and higher liver levels of OEA and PEA. It failed in mice lacking liver SIRT1. CB1 regulated p53 and miR-22, which targets SIRT1 and PPAR-alpha.

Limits of this study

A mouse and cell study; it cannot show effect in people. PEA was measured as a liver lipid, not given. Funding and conflicts not stated in the abstract.

Source

PubMed 32987186 · doi:10.1016/j.molmet.2020.101087

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.