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Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
Published on: March 17, 2023
Integrin-linked kinase promotes hepatic fat accumulation via F-actin stabilization-dependent CD36 plasma membrane
Kakali Ghoshal1, Fabian Bock1,2, Nathan C Winn3,4
1Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University School of Medicine, Nashville, TN, USA.
Iscience
|July 28, 2026
Summary
Integrin-linked kinase (ILK) promotes fatty liver in high-fat diets by stabilizing F-actin. This actin stabilization enhances fatty acid uptake via CD36, leading to increased liver lipids and insulin resistance.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Diseases
Background:
- High-fat diet (HFD) induces insulin resistance with increased hepatic lipid accumulation.
- Integrin-linked kinase (ILK) is implicated in HFD-induced hepatic insulin resistance and triglyceride content.
- The precise mechanism by which ILK promotes hepatic fatty acid accumulation remains unclear.
Purpose of the Study:
- To investigate the mechanistic link between ILK-mediated F-actin stabilization and hepatic fatty acid uptake.
- To determine if ILK regulates the localization of the fatty acid transporter CD36 through F-actin.
Main Methods:
- Utilized high-fat diet (HFD)-fed mice lacking ILK in hepatocytes.
- Employed F-actin stabilizer (jasplakinolide) in ILK-null cells.
- Assessed hepatic F-actin abundance, CD36 plasma membrane localization, and intracellular lipid accumulation.
- Investigated the effect of CD36 inhibition on lipid uptake.
Main Results:
- Hepatocyte-specific ILK deficiency in HFD mice reduced hepatic F-actin, CD36 plasma membrane localization, and lipid accumulation.
- Jasplakinolide treatment in ILK-null cells increased F-actin, CD36 membrane association, and lipid uptake.
- CD36 inhibition abrogated the increased lipid uptake in jasplakinolide-treated ILK-null cells.
Conclusions:
- ILK regulates intracellular lipid transport by connecting CD36 to the F-actin cytoskeleton.
- ILK-mediated F-actin stabilization is a key mechanism driving hepatic fatty acid uptake and accumulation in HFD-induced insulin resistance.
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