Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Aging cell, 2020-06, Vol.19 (6), p.e13150-n/a

Ort / Verlag

London: John Wiley & Sons, Inc

Erscheinungsjahr

2020

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. 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.