Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate.

ABSTRACT: Obesity is characterized by excessive fatty acid conversion to triacylglycerols (TAGs) in adipose tissues. However, how signaling networks sense fatty acids and connect to the stimulation of lipid synthesis remains elusive. Here, we show that homozygous knock-in mice carrying a point mutation at the Ser⁸⁶ phosphorylation site of acetyltransferase Tip60 (Tip60 ^SA/SA ) display remarkably reduced body fat mass, and Tip60 ^SA/SA females fail to nurture pups to adulthood due to severely reduced milk TAGs. Mechanistically, fatty acids stimulate Tip60-dependent acetylation and endoplasmic reticulum translocation of phosphatidic acid phosphatase lipin 1 to generate diacylglycerol for TAG synthesis, which is repressed by deacetylase Sirt1. Inhibition of Tip60 activit

SUBMITTER: Li TY 

PROVIDER: S-EPMC5953937 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature