Abstract
The switching defective/sucrose non-fermenting (SWI/SNF) complexes play an important role in hepatic lipid metabolism regulating both transcriptional activation and repression. BAF60a is a core subunit of the SWI/SNF chromatin-remodeling complexes that activates the transcription of fatty acid oxidation genes during fasting/glucagon. BAF60c, another subunit of SWI/SNF complexes, is recruited to form the lipoBAF complex that activates lipogenic genes, promoting lipogenesis and increasing the triglyceride level in response to feeding/insulin. Interestingly, hepatocytes located in the periportal and perivenous zones of the liver display a remarkable heterogeneity in the activity of various enzymes, metabolic functions and gene expression. Especially, fatty-acid oxidation was shown to be mostly periportal, whereas lipogenesis was mostly perivenous. Therefore, the present review highlights the role of of SWI/SNF regulating lipid metabolism under nutritional and hormonal control, which may be associated with hepatocyte heterogeneity.
Highlights
Understanding the regulation of hepatic lipid metabolism is critical as this metabolic disorder is often linked to chronic pathological conditions such as fatty liver, obesity, diabetes and cardiovascular disease [1, 2]
Studies have shown that peroxisome proliferatoractivated receptor-α (PPARα) plays a key role in he transcriptional control of encoding genes related to lipid metabolism in the liver, including those involved in mitochondrial β-oxidation, peroxisomal β-oxidation, fatty acid uptake and/or binding, and lipoprotein assembly and transport [86,87,88,89]
Fatty acids serve as an important source of energy as well as energy storage for many organisms and are pivotal for a variety of biological processes, including the synthesis of cellular membrane lipids and generation of lipid-containing messengers involved in signal transduction [140]
Summary
Understanding the regulation of hepatic lipid metabolism is critical as this metabolic disorder is often linked to chronic pathological conditions such as fatty liver, obesity, diabetes and cardiovascular disease [1, 2]. BAF60a and BAF60c, two subunits of the SWI/SNF chromatin-remodeling complexes, are important for maintaining hepatic lipid metabolism. Studies have identified BAF60a and PPARα interacts with PGC-1α for the formation of a transcriptional complex to transcriptional activation of fatty acid oxidation genes during fasting [17].
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