Objective: Adipose dysfunction affects the secretion of adipokines and mediates the hepatic physiological changes. Fat mass and obesity associated protein (FTO) plays a crucial part in fat deposition but the crosstalk between FTO-mediated secretion of adipokines and hepatic steatosis is not clear.
Methods: Firstly, adipose-selective FTO knockout (FTO) and control (FTO) mice were induced by high fat diet (HFD). Then qRT-PCR assay was performed to analyze the expressions of hepatic lipid metabolism genes and adipocytokines gene of inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT). Afterwards, 3T3-L1 cells were knocked out IL-6 and co-cultured with AML12 cells (3T3-L1 siIL-6/AML12) and the expressions of hepatic lipid lipolysis genes were measured. Finally, we detected the hepatic lipid metabolism genes expressions in AML12 cells with the medium from 3T3-L1 cells or IL-6 treatment.
Results: FTO effectively alleviated HFD-induced hepatic steatosis in mice and improved the transcription level of genes involved in hepatic lipolysis. Further investigation demonstrated that FTO knockout increased level of IL-6 in adipose tissues and 3T3-L1 cells. Compared to 3T3-L1/AML12, our results showed lipolysis-related genes expressions were dramatically inhibited in 3T3-L1 siIL-6/AML12. Finally, both depletion of FTO in adipocytes and IL-6 supplement led to increased lipolysis genes expressions in AML12 cells.
Conclusions: FTO knockout in adipose tissue alleviated hepatic steatosis via targeting adipocyte-derived IL-6.
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| http://dx.doi.org/10.1016/j.gene.2022.146224 | DOI Listing |
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