Caenorhabditis elegans Lipin 1 moderates the lifespan‐shortening effects of dietary glucose by maintaining ω‐6 polyunsaturated fatty acids. Issue 6 (31st May 2020)

• Record Type: Journal Article
• Authors: Jung, Yoonji; Kwon, Sujeong; Ham, Seokjin; Lee, Dongyeop; Park, Hae‐Eun H.; Yamaoka, Yasuyo; Jeong, Dae‐Eun; Artan, Murat; Altintas, Ozlem; Park, Sangsoon; Hwang, Wooseon; Lee, Yujin; Son, Heehwa G.; An, Seon Woo A.; Kim, Eun Ji E.; Seo, Mihwa; Lee, Seung‐Jae V.
• Is Part Of: Aging cell. Volume 19:Issue 6(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-05-31
• Subjects: aging -- C. elegans -- glucose -- LPIN‐1 -- metabolism -- ω‐6 polyunsaturated fatty acids; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.13150
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: 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 ω‐6 polyunsaturated fatty acids (PUFAs), linoleic acid and arachidonic acid, were increased by knockdown of lpin‐1 but decreased by glucose feeding. Importantly, these ω‐6 PUFAs attenuated the short lifespan of glucose‐fed lpin‐1 ‐inhibited animals. Thus, the production of ω‐6 PUFAs is crucial for protecting animals from living very short under glucose‐rich conditions. Abstract : LPIN‐1, phosphatidic acid phosphatase and potential transcriptional regulator, ameliorates lifespan‐shortening effects of dietary glucose by maintaining lipidostasis. Genetic inhibition of lpin ‐ 1 causes lipidostasis imbalance, including substantial reduction in the levels of ω‐6 polyunsaturated fatty acids (PUFAs), linoleic acid and arachidonic acid, in glucose‐rich conditions. This leads to substantially decreased lifespan due to increased glucose toxicity.