AI Article Synopsis
- The liver plays a crucial role in maintaining energy balance, but excessive fat production from a high-calorie diet can lead to fatty liver diseases and other metabolic issues.
- The study identifies the enzyme retinol saturase (RetSat) as a key factor in the development of fatty liver, with its levels linked to fat and triglyceride levels in humans.
- Targeting RetSat could potentially be a new treatment strategy for fatty liver conditions by affecting the activity of a transcription factor involved in fat production, known as ChREBP.
Article Abstract
The liver integrates multiple metabolic pathways to warrant systemic energy homeostasis. An excessive lipogenic flux due to chronic dietary stimulation contributes to the development of hepatic steatosis, dyslipidemia and hyperglycemia. Here we show that the oxidoreductase retinol saturase (RetSat) is involved in the development of fatty liver. Hepatic RetSat expression correlates with steatosis and serum triglycerides (TGs) in humans. Liver-specific depletion of RetSat in dietary obese mice lowers hepatic and circulating TGs and normalizes hyperglycemia. Mechanistically, RetSat depletion reduces the activity of carbohydrate response element binding protein (ChREBP), a cellular hexose-phosphate sensor and inducer of lipogenesis. Defects upon RetSat depletion are rescued by ectopic expression of ChREBP but not by its putative enzymatic product 13,14-dihydroretinol, suggesting that RetSat affects hepatic glucose sensing independent of retinol conversion. Thus, RetSat is a critical regulator of liver metabolism functioning upstream of ChREBP. Pharmacological inhibition of liver RetSat may represent a therapeutic approach for steatosis.Fatty liver is one of the major features of metabolic syndrome and its development is associated with deregulation of systemic lipid and glucose homeostasis. Here Heidenreich et al. show that retinol saturase is implicated in hepatic lipid metabolism by regulating the activity of the transcription factor ChREBP.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577314 | PMC |
| http://dx.doi.org/10.1038/s41467-017-00430-w | DOI Listing |
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