The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify the direct targets of ChREBP on a genome-wide scale and provide more insight into the mechanism by which ChREBP regulates glucose-responsive gene expression, we performed chromatin immunoprecipitation-sequencing and gene expression analysis. We identified 1153 ChREBP binding sites and 783 target genes using the chromatin from HepG2, a human hepatocellular carcinoma cell line. A motif search revealed a refined consensus sequence (CABGTG-nnCnG-nGnSTG) to better represent critical elements of a functional ChREBP binding sequence. Gene ontology analysis shows that ChREBP target genes are particularly associated with lipid, fatty acid and steroid metabolism. In addition, other functional gene clusters related to transport, development and cell motility are significantly enriched. Gene set enrichment analysis reveals that ChREBP target genes are highly correlated with genes regulated by high glucose, providing a functional relevance to the genome-wide binding study. Furthermore, we have demonstrated that ChREBP may function as a transcriptional repressor as well as an activator.

Significance: There is a growing appreciation for a fundamental connection between lipid metabolism and the innate immune response. Phagocytosis is a key macrophage innate immune response to pathogen exposure, and cytoplasmic membrane expansion is required to surround and capture the target pathogen prior to internalization. Sterol regulatory element binding proteins (SREBPs) are gene regulatory factors that sense the intracellular lipid environment and modulate key genes that drive fatty acid and cholesterol synthesis to maintain lipid homeostasis. In this study, we show that, in mutant cells that lack a key SREBP isoform, phagocytosis is impaired, and we track the defect to altered lipid composition of membrane phospholipids that results in decreased interaction between membrane lipid rafts and the actin cytoskeletal network.

Most people start their day with a cup of coffee. Many people would also finish their daily work with coffee. As such, coffee drinking is an important part of modern daily life. It has been told that coffee is a driving force for humans to develop science, because it has an alerting effect on the human brain. However, some people report experiencing irregular heartbeat or headaches and are thus reluctant to drink coffee, which suggests individual variation to coffee intolerance. The aim of this review is to briefly summarize the effects of coffee on human health.

Sterol regulatory element binding protein (SREBP) cleavage activating protein (SCAP) is a key regulator of SREBP maturation. SCAP induces translocation of SREBP from the endoplasmic reticulum to the Golgi apparatus, allowing it to regulate cellular triglyceride and cholesterol levels. Previous studies have shown that suppression of SREBP activation in SCAP conditional knockout mice reduced the accumulation of intracellular triglycerides, which eventually causes the development of metabolic diseases such as atherosclerosis, diabetes, hepatic steatosis, and insulin resistance. However, despite the significance of SCAP as a regulator of SREBP, its function has not been thoroughly discussed. In this review, we have summarized the function of SCAP and its regulatory proteins. Furthermore, we discuss recent studies regarding SCAP as a possible therapeutic target for hypertriglyceridemia and hyperlipidemia.

The gene expression of glucose transporter type 4 isoform (GLUT4) is known to be controlled by metabolic, nutritional, or hormonal status. Understanding the molecular mechanisms governing GLUT4 gene expression is critical, because glucose disposal in the body depends on the activities of GLUT4 in the muscle and adipocytes. The GLUT4 activities are regulated by a variety of mechanisms. One of them is transcriptional regulation. GLUT4 gene expression is regulated by a variety of transcriptional factors in muscle and adipose tissue. These data are accumulating regarding the transcriptional factors regulating GLUT4 gene expression. These include MyoD, MEF2A, GEF, TNF‐α, TR‐1α, KLF15, SREBP‐1c, C/EBP‐α, O/E‐1, free fatty acids, PAPRγ, LXRα, NF‐1, etc. These factors are involved in the positive or negative regulation of GLUT4 gene expression. In addition, there is a complex interplay between these factors in transactivating GLUT4 promoter activity. Understanding the mechanisms controlling GLUT4 gene transcription in these tissues will greatly promote the potential therapeutic drug development for obesity and T2DM. IUBMB Life, 59: 134‐145, 2007