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Updated: Oct 21, 2025
Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
Loss of SNORA73 reprograms cellular metabolism and protects against steatohepatitis
Arthur C Sletten1, Jessica W Davidson2, Busra Yagabasan2
1Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Abstract:
Dyslipidemia and resulting lipotoxicity are pathologic signatures of metabolic syndrome and type 2 diabetes. Excess lipid causes cell dysfunction and induces cell death through pleiotropic mechanisms that link to oxidative stress. However, pathways that regulate the response to metabolic stress are not well understood. Herein, we show that disruption of the box H/ACA SNORA73 small nucleolar RNAs encoded within the small nucleolar RNA hosting gene 3 (Snhg3) causes resistance to lipid-induced cell death and general oxidative stress in cultured cells. This protection from metabolic stress is associated with broad reprogramming of oxidative metabolism that is dependent on the mammalian target of rapamycin signaling axis. Furthermore, we show that knockdown of SNORA73 in vivo protects against hepatic steatosis and lipid-induced oxidative stress and inflammation. Our findings demonstrate a role for SNORA73 in the regulation of metabolism and lipotoxicity.
Insights
Disrupting SNORA73 small nucleolar RNAs protects cells from lipid-induced death and oxidative stress. This finding reveals a new role for SNORA73 in regulating metabolism and lipotoxicity in conditions like metabolic syndrome.
Area of Science:
- Molecular Biology
- Metabolic Disease Research
- Cellular Stress Response
Background:
- Dyslipidemia and lipotoxicity are key features of metabolic syndrome and type 2 diabetes.
- Excess lipids cause cellular dysfunction and death via oxidative stress, but regulatory pathways remain unclear.
Purpose of the Study:
- To investigate the role of SNORA73 small nucleolar RNAs in cellular responses to metabolic stress.
- To elucidate the mechanisms by which SNORA73 influences lipotoxicity and oxidative stress.
Main Methods:
- Utilized cultured cells to study the effects of SNORA73 disruption on lipid-induced cell death and oxidative stress.
- Investigated the involvement of the mammalian target of rapamycin (mTOR) signaling pathway.
- Performed in vivo studies involving knockdown of SNORA73 in a model of hepatic steatosis.
Main Results:
- Disruption of SNORA73 conferred resistance to lipid-induced cell death and oxidative stress.
- Protection was linked to reprogramming of oxidative metabolism via the mTOR pathway.
- In vivo SNORA73 knockdown reduced hepatic steatosis, oxidative stress, and inflammation.
Conclusions:
- SNORA73 plays a significant role in regulating cellular responses to metabolic stress and lipotoxicity.
- Targeting SNORA73 may offer a novel therapeutic strategy for metabolic syndrome and related diseases.
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