Caenorhabditis elegans Lipin 1 moderates the lifespan-shortening effects of dietary glucose by maintaining ω-6 polyunsaturated fatty acids.

Excessive glucose causes various diseases and decreases lifespan by altering metabolic processes, but underlying mechanisms remain incompletely understood. Here, we show that Lipin 1/LPIN-1, a phosphatidic acid phosphatase and a putative transcriptional coregulator, prevents life-shortening effects of dietary glucose on Caenorhabditis elegans. We found that depletion of lpin-1 decreased overall lipid levels, despite increasing the expression of genes that promote fat synthesis and desaturation, and downregulation of lipolysis. We then showed that knockdown of lpin-1 altered the composition of various fatty acids in the opposite direction of dietary glucose. In particular, the levels of two omega-6 polyunsaturated fatty acids (PUFAs), linoleic acid and arachidonic acid, were increased by knockdown of lpin-1 but decreased by glucose feeding. Importantly, these omega-6 PUFAs attenuated the short lifespan of glucose-fed lpin-1-inhibited animals. Thus, the production of omega-6 PUFAs is crucial for protecting animals from living very short under glucose-rich conditions.