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TOPLINE:
that contributes to liver fibrosis and progression to cirrhosis and liver cancer, new data suggest.
METHODOLOGY:
- Because omega-3 polyunsaturated fatty acids have been shown to reduce hepatic dysfunction in NASH, but the molecular underpinnings of this action were elusive, researchers conducted a multiomic network analysis applied to a mouse model of Western diet–induced NASH to identify the key mechanisms involved.
- They also performed a meta-analysis of human liver cancer transcriptome data to evaluate which aspects of NASH pathogenesis leading to cancer are reversed by omega-3 polyunsaturated fatty acids.
TAKEAWAY:
- BTC, an epidermal growth factor–binding protein, was consistently upregulated in liver cancer and downregulated by omega-3 polyunsaturated fatty acids in mice and humans with NASH.
- BTC promotes NASH fibrosis by activating dormant hepatic stellate cells to produce transforming growth factor beta-2 and increase collagen production. It also exacerbates toll-like receptor-dependent inflammatory processes in NASH.
- By downregulating BTC, omega-3 polyunsaturated fatty acids have therapeutic potential in NASH and could serve as a novel drug target.
IN PRACTICE:
“BTC represents a candidate master regulator inducing two most important factors (collagens and integrins) contributing to liver fibrosis and consequently promoting liver cancer,” the researchers write. “Future studies should investigate if BTC-triggered gene expression signatures can serve as biomarkers guiding personalized [omega-3 polyunsaturated fatty acid] therapy, as targets of new NAFLD/NASH drugs, and finally as a predictors of hepatic cancer risk in humans.”
SOURCE:
The study, with lead first author Jyothi Padiadpu, PhD, Oregon State University College of Pharmacy, Corvallis, was published online in EMBO Molecular Medicine (2023. doi: 10.15252/emmm.202318367).
LIMITATIONS:
The study authors report no limitations. However, the findings are based on mouse model and human transcriptome data.
DISCLOSURES:
This research was supported by the National Institute of Diabetes and Digestive Kidney Diseases and the U.S. Department of Agriculture. The authors report no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
that contributes to liver fibrosis and progression to cirrhosis and liver cancer, new data suggest.
METHODOLOGY:
- Because omega-3 polyunsaturated fatty acids have been shown to reduce hepatic dysfunction in NASH, but the molecular underpinnings of this action were elusive, researchers conducted a multiomic network analysis applied to a mouse model of Western diet–induced NASH to identify the key mechanisms involved.
- They also performed a meta-analysis of human liver cancer transcriptome data to evaluate which aspects of NASH pathogenesis leading to cancer are reversed by omega-3 polyunsaturated fatty acids.
TAKEAWAY:
- BTC, an epidermal growth factor–binding protein, was consistently upregulated in liver cancer and downregulated by omega-3 polyunsaturated fatty acids in mice and humans with NASH.
- BTC promotes NASH fibrosis by activating dormant hepatic stellate cells to produce transforming growth factor beta-2 and increase collagen production. It also exacerbates toll-like receptor-dependent inflammatory processes in NASH.
- By downregulating BTC, omega-3 polyunsaturated fatty acids have therapeutic potential in NASH and could serve as a novel drug target.
IN PRACTICE:
“BTC represents a candidate master regulator inducing two most important factors (collagens and integrins) contributing to liver fibrosis and consequently promoting liver cancer,” the researchers write. “Future studies should investigate if BTC-triggered gene expression signatures can serve as biomarkers guiding personalized [omega-3 polyunsaturated fatty acid] therapy, as targets of new NAFLD/NASH drugs, and finally as a predictors of hepatic cancer risk in humans.”
SOURCE:
The study, with lead first author Jyothi Padiadpu, PhD, Oregon State University College of Pharmacy, Corvallis, was published online in EMBO Molecular Medicine (2023. doi: 10.15252/emmm.202318367).
LIMITATIONS:
The study authors report no limitations. However, the findings are based on mouse model and human transcriptome data.
DISCLOSURES:
This research was supported by the National Institute of Diabetes and Digestive Kidney Diseases and the U.S. Department of Agriculture. The authors report no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
that contributes to liver fibrosis and progression to cirrhosis and liver cancer, new data suggest.
METHODOLOGY:
- Because omega-3 polyunsaturated fatty acids have been shown to reduce hepatic dysfunction in NASH, but the molecular underpinnings of this action were elusive, researchers conducted a multiomic network analysis applied to a mouse model of Western diet–induced NASH to identify the key mechanisms involved.
- They also performed a meta-analysis of human liver cancer transcriptome data to evaluate which aspects of NASH pathogenesis leading to cancer are reversed by omega-3 polyunsaturated fatty acids.
TAKEAWAY:
- BTC, an epidermal growth factor–binding protein, was consistently upregulated in liver cancer and downregulated by omega-3 polyunsaturated fatty acids in mice and humans with NASH.
- BTC promotes NASH fibrosis by activating dormant hepatic stellate cells to produce transforming growth factor beta-2 and increase collagen production. It also exacerbates toll-like receptor-dependent inflammatory processes in NASH.
- By downregulating BTC, omega-3 polyunsaturated fatty acids have therapeutic potential in NASH and could serve as a novel drug target.
IN PRACTICE:
“BTC represents a candidate master regulator inducing two most important factors (collagens and integrins) contributing to liver fibrosis and consequently promoting liver cancer,” the researchers write. “Future studies should investigate if BTC-triggered gene expression signatures can serve as biomarkers guiding personalized [omega-3 polyunsaturated fatty acid] therapy, as targets of new NAFLD/NASH drugs, and finally as a predictors of hepatic cancer risk in humans.”
SOURCE:
The study, with lead first author Jyothi Padiadpu, PhD, Oregon State University College of Pharmacy, Corvallis, was published online in EMBO Molecular Medicine (2023. doi: 10.15252/emmm.202318367).
LIMITATIONS:
The study authors report no limitations. However, the findings are based on mouse model and human transcriptome data.
DISCLOSURES:
This research was supported by the National Institute of Diabetes and Digestive Kidney Diseases and the U.S. Department of Agriculture. The authors report no conflicts of interest.
A version of this article appeared on Medscape.com.