The mitochondrial fission protein Drp1 in liver is required to mitigate NASH and prevents the activation of the mitochondrial ISR.

First, we observed a significant decrease in complex 1 and a decreasing trend in complex 2 driven respiration in NAG-Drp1si mice after correction per mitochondrial content with MTDR [ 19 ], while no changes were observed in total complex 4 function ( Figure 2 B).

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In this regard, Drp1si mitochondria from GAN-fed mice even showed a trend to be larger than mitochondria from chow diet fed mice ( Figure 4 B,C).

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When looking at NEFA composition, NAG-Drp1si treated mice showed a highly significant increase in intrahepatic oleate content, but only an increasing trend in palmitate content.

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