Targeted Induction of Ceramide Degradation Leads to Improved Systemic Metabolism and Reduced Hepatic Steatosis.

Abstract:

:Sphingolipids have garnered attention for their role in insulin resistance and lipotoxic cell death. We have developed transgenic mice inducibly expressing acid ceramidase that display a reduction in ceramides in adult mouse tissues. Hepatic overexpression of acid ceramidase prevents hepatic steatosis and prompts improvements in insulin action in liver and adipose tissue upon exposure to high-fat diet. Conversely, overexpression of acid ceramidase within adipose tissue also prevents hepatic steatosis and systemic insulin resistance. Induction of ceramidase activity in either tissue promotes a lowering of hepatic ceramides and reduced activation of the ceramide-activated protein kinase C isoform PKCζ, though the induction of ceramidase activity in the adipocyte prompts more rapid resolution of hepatic steatosis than overexpression of the enzyme directly in the liver. Collectively, our observations suggest the existence of a rapidly acting "cross-talk" between liver and adipose tissue sphingolipids, critically regulating glucose metabolism and hepatic lipid uptake.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Xia JY,Holland WL,Kusminski CM,Sun K,Sharma AX,Pearson MJ,Sifuentes AJ,McDonald JG,Gordillo R,Scherer PE

doi

10.1016/j.cmet.2015.06.007

subject

Has Abstract

pub_date

2015-08-04 00:00:00

pages

266-278

issue

2

eissn

1550-4131

issn

1932-7420

journal_volume

22

pub_type

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