Fig. 8: Proposed model of reversion of obesity and obesity-related hepatosteatosis by Mat1a antisense oligonucleotides. | Nature Communications

Fig. 8: Proposed model of reversion of obesity and obesity-related hepatosteatosis by Mat1a antisense oligonucleotides.

From: Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis

Fig. 8: Proposed model of reversion of obesity and obesity-related hepatosteatosis by Mat1a antisense oligonucleotides.The alternative text for this image may have been generated using AI.

Mat1a deficiency leads to a reduction in glutathione levels, leading to ROS accumulation in hepatocytes. The increased ROS levels modifies KEAP1, triggering NRF2 release to the nucleus. NRF2 induces transcription of target genes including FGF21. The increased FGF21 expression and secretion to the circulation induces BAT thermogenesis, lipolysis and release of fatty acids from white adipose tissue (WAT) to the blood. Lipids released to plasma as very-low-density lipoproteins (VLDL), free fatty acids and dietary lipids (chylomicrons) are channeled to the BAT to be used as energy source in the fatty acid oxidation. The increased FGF21 also reduces liver triglyceride storage and de novo lipogenesis. Thus, the NRF2-induced FGF21 secretion reverses obesity protecting from insulin resistance, hepatosteatosis and reducing plasma lipid levels. This picture was designed using BioRender graphic tool (BioRender.com).

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