We have located links that may give you full text access.
Src homology 3 domain binding kinase 1 protects against hepatic steatosis and insulin resistance through the Nur77-FGF21 pathway.
Hepatology : Official Journal of the American Association for the Study of Liver Diseases 2022 April 2
BACKGROUND AND AIMS: Metabolism in the liver is dysregulated in obesity, contributing to various health problems including steatosis and insulin resistance. While the pathogenesis of lipid accumulation has been extensively studied, the protective mechanism against lipid challenge in the liver remains unclear. Here, we report that Src homology 3 domain binding kinase 1 (SBK1) is a regulator of hepatic lipid metabolism and systemic insulin sensitivity in response to obesity.
APPROACH AND RESULTS: Enhanced Sbk1 expression was found in the liver of high-fat diet (HFD)-induced obese mice and fatty acid (FA)-challenged hepatocytes. SBK1 knockdown in mouse liver cells augmented FA uptake and lipid accumulation. Similarly, liver-specific SBK1 knockout (Lsko) mice displayed more severe hepatosteatosis and higher expression of genes in FA uptake and lipogenesis than the Flox/Flox (Fl/Fl) control mice when fed the HFD. The HFD-fed Lsko mice also showed symptoms of hyperglycemia, poor systemic glucose tolerance, and lower insulin sensitivity than the Fl/Fl mice. On the other hand, hepatic Sbk1 overexpression alleviated the high-fructose diet-induced hepatosteatosis, hyperlipidemia, and hyperglycemia in mice. White adipose tissue browning was also observed in hepatic SBK1-overexpressed mice. Moreover, we found that SBK1 was a positive regulator of FGF21 in the liver during energy surplus conditions. Mechanistically, SBK1 phosphorylates the orphan nuclear receptor 4A1 (Nur77) on serine 344 to promote hepatic FGF21 expression and inhibit the transcription of genes involved in lipid anabolism.
CONCLUSIONS: Collectively, our data suggest that SBK1 is a regulator of the metabolic adaption against obesity through the Nur77-FGF21 pathway.
APPROACH AND RESULTS: Enhanced Sbk1 expression was found in the liver of high-fat diet (HFD)-induced obese mice and fatty acid (FA)-challenged hepatocytes. SBK1 knockdown in mouse liver cells augmented FA uptake and lipid accumulation. Similarly, liver-specific SBK1 knockout (Lsko) mice displayed more severe hepatosteatosis and higher expression of genes in FA uptake and lipogenesis than the Flox/Flox (Fl/Fl) control mice when fed the HFD. The HFD-fed Lsko mice also showed symptoms of hyperglycemia, poor systemic glucose tolerance, and lower insulin sensitivity than the Fl/Fl mice. On the other hand, hepatic Sbk1 overexpression alleviated the high-fructose diet-induced hepatosteatosis, hyperlipidemia, and hyperglycemia in mice. White adipose tissue browning was also observed in hepatic SBK1-overexpressed mice. Moreover, we found that SBK1 was a positive regulator of FGF21 in the liver during energy surplus conditions. Mechanistically, SBK1 phosphorylates the orphan nuclear receptor 4A1 (Nur77) on serine 344 to promote hepatic FGF21 expression and inhibit the transcription of genes involved in lipid anabolism.
CONCLUSIONS: Collectively, our data suggest that SBK1 is a regulator of the metabolic adaption against obesity through the Nur77-FGF21 pathway.
Full text links
Related Resources
Trending Papers
Guillain-Barré syndrome: History, pathogenesis, treatment, and future directions.European Journal of Neurology 2024 May 17
Contrast-induced acute kidney injury: a review of definition, pathogenesis, risk factors, prevention and treatment.BMC Nephrology 2024 April 23
Angiotensin Receptor Blocker-Neprilysin Inhibitor for Heart Failure with Reduced Ejection Fraction.Pharmacological Research : the Official Journal of the Italian Pharmacological Society 2024 May 12
The Therapy and Management of Heart Failure with Preserved Ejection Fraction: New Insights on Treatment.Cardiac Failure Review 2024
European Respiratory Society Clinical Practice Guideline on symptom management for adults with serious respiratory illness.European Respiratory Journal 2024 May 9
Axillary Surgery for Breast Cancer in 2024.Cancers 2024 April 24
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app