• BMB Reports
• /
• v.51 no.9
• /
• pp.429-436
• /
• 2018

Fructose in the form of sucrose and high fructose corn syrup is absorbed by the intestinal transporter and mainly metabolized in the small intestine. However, excess intake of fructose overwhelms the absorptive capacity of the small intestine, leading to fructose malabsorption. Carbohydrate response element-binding protein (ChREBP) is a basic helix-loop-helix leucine zipper transcription factor that plays a key role in glycolytic and lipogenic gene expression in response to carbohydrate consumption. While ChREBP was initially identified as a glucose-responsive factor in the liver, recent evidence suggests that ChREBP is essential for fructose-induced lipogenesis and gluconeogenesis in the small intestine as well as in the liver. We recently identified that the loss of ChREBP leads to fructose intolerance via insufficient induction of genes involved in fructose transport and metabolism in the intestine. As fructose consumption is increasing and closely associated with metabolic and gastrointestinal diseases, a comprehensive understanding of cellular fructose sensing and metabolism via ChREBP may uncover new therapeutic opportunities. In this mini review, we briefly summarize recent progress in intestinal fructose metabolism, regulation and function of ChREBP by fructose, and delineate the potential mechanisms by which excessive fructose consumption may lead to irritable bowel syndrome.

• Molecules and Cells
• /
• v.43 no.5
• /
• pp.419-430
• /
• 2020

The liver is an important organ in the regulation of glucose and lipid metabolism. It is responsible for systemic energy homeostasis. When energy need exceeds the storage capacity in the liver, fatty acids are shunted into nonoxidative sphingolipid biosynthesis, which increases the level of cellular ceramides. Accumulation of ceramides alters substrate utilization from glucose to lipids, activates triglyceride storage, and results in the development of both insulin resistance and hepatosteatosis, increasing the likelihood of major metabolic diseases. Another sphingolipid metabolite, sphingosine 1-phosphate (S1P) is a bioactive signaling molecule that acts via S1P-specific G protein coupled receptors. It regulates many cellular and physiological events. Since an increase in plasma S1P is associated with obesity, it seems reasonable that recent studies have provided evidence that S1P is linked to lipid pathophysiology, including hepatosteatosis and fibrosis. Herein, we review recent findings on ceramides and S1P in obesity-mediated liver diseases and the therapeutic potential of these sphingolipid metabolites.

• Biomedical Science Letters
• /
• v.14 no.4
• /
• pp.233-238
• /
• 2008

Gestational diabetes mellitus (GDM) is a common complication during pregnancy and one of the main causes of adverse fetal-maternal outcomes. However, the pathogenesis of GDM has not been clearly stated. Adiponectin, an adipose tissue-derived plasma protein, is involved in regulation of insulin resistance and glucose hemostasis, and thus is a key modulator of insulin action and glucose metabolism. In this study, we investigated to compare serum adiponectin levels in pregnant women with diabetes, pregnant women who are without diabetes, and non-pregnant women, and to evaluate relationship between serum adiponectin. levels and metabolic parameters. Forty-one pregnant women with diabetes, fifty-nine pregnant women without diabetes and forty non-pregnancy women were recruited. Adiponectin levels were significantly lower in pregnant women with diabetes when compared to non-pregnant women and pregnant women without diabetes. Pregnant women without diabetes at second trimester had lower adiponectin levels compared to non-pregnant women. Adiponectin was negatively correlated with BMI, fasting insulin, HOMA-IR, total cholesterol, and triglyceride. In conclusion, this study confirmed that the decreased level of adiponectin precedes the onset of abnormal glucose level during pregnancy and also normal pregnant women had lower adiponectin levels compared to non-pregnant women. This knowledge may help to identify strategies for lowering the occurrence of GDM in women who are at high risk of developing the disorder.

• The Plant Pathology Journal
• /
• v.18 no.2
• /
• pp.57-62
• /
• 2002

In vivo expression technology (IVET) has been developed to study bacterial gene expression in Salmonella typhimurium during host infection. The expression of selected genes by IVET has been elevated in vivo but not in vitro. The selected genes turned out to be important for bacterial virulence and/or pathogenicity. IVET depends on a synthetic operon with a promoterless transcriptional fusion between a selection marker gene and a reporter gene. The IVET approach has been successfully adapted in other bacterial pathogens and plant-associated bacteria using different selection markers. Pseudomonas putida suppresses citrus root rot caused by Phytophthora parasitica and enhances citrus seedling growth. The WET strategy was adapted based on a transcriptional fusion, pyrBC'-lacZ, in P. putida to study the bacterial traits important far biocontrol activities. Several genes appeared to be induced on P. parasitica hyphae and were found to be related with metabolism and regulation of gene expression. It is likely that the biocontrol strain took a metabolic advantage from the plant pathogenic fungus and then suppressed citrus root rot effectively. The result was parallel with those from the adaptation of IVET in P. fluorescens, a plant growth promoting rhizobacteria (PGPR). Interestingly, genes encoding components for type III secretion system have been identified as rhizosphere-induced genes in the PGPR strain. The type III secretion system may play a certain role during interaction with its counterpart plants. Application of IVET has been demonstrated in a wide range of bacteria. It is an important strategy to genetically understand complicated bacterial traits in the environment.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.19 no.4
• /
• pp.221-228
• /
• 2016

The gastrointestinal exposome represents the integration of all xenobiotic components and host-derived endogenous components affecting the host health, disease progression and ultimately clinical outcomes during the lifespan. The human gut microbiome as a dynamic exposome of commensalism continuously interacts with other exogenous exposome as well as host sentineling components including the immune and neuroendocrine circuit. The composition and diversity of the microbiome are established on the basis of the luminal environment (physical, chemical and biological exposome) and host surveillance at each part of the gastrointestinal lining. Whereas the chemical exposome derived from nutrients and other xenobiotics can influence the dynamics of microbiome community (the stability, diversity, or resilience), the microbiomes reciprocally alter the bioavailability and activities of the chemical exposome in the mucosa. In particular, xenobiotic metabolites by the gut microbial enzymes can be either beneficial or detrimental to the host health although xenobiotics can alter the composition and diversity of the gut microbiome. The integration of the mucosal crosstalk in the exposome determines the fate of microbiome community and host response to the etiologic factors of disease. Therefore, the network between microbiome and other mucosal exposome would provide new insights into the clinical intervention against the mucosal or systemic disorders via regulation of the gut-associated immunological, metabolic, or neuroendocrine system.

• Journal of Microbiology and Biotechnology
• /
• v.26 no.5
• /
• pp.967-974
• /
• 2016

Zearalenone (ZEA) is an estrogenic mycotoxin that is produced by several Fusarium species, including Fusarium graminearum. One of the ZEA biosynthetic genes, ZEB2, encodes two isoforms of Zeb2 by alternative transcription, forming an activator (Zeb2L-Zeb2L homooligomer) and an inhibitor (Zeb2L-Zeb2S heterodimer) that directly regulate the ZEA biosynthetic genes in F. graminearum. Cyclic AMP-dependent protein kinase A (PKA) signaling regulates secondary metabolic processes in several filamentous fungi. In this study, we investigated the effects of the PKA signaling pathway on ZEA biosynthesis. Through functional analyses of PKA catalytic and regulatory subunits (CPKs and PKR), we found that the PKA pathway negatively regulates ZEA production. Genetic and biochemical evidence further demonstrated that the PKA pathway specifically represses ZEB2L transcription and also takes part in posttranscriptional regulation of ZEB2L during ZEA production. Our findings reveal the intriguing mechanism that the PKA pathway regulates secondary metabolite production by reprograming alternative transcription.

• Journal of Embryo Transfer
• /
• v.31 no.4
• /
• pp.319-322
• /
• 2016

CD26, also known as Dipeptidyl peptidase IV (DPP-4), is a cell surface glycoprotein that belongs to the serine protease family and has wide spread organ distribution throughout the body. CD26 was previously characterized in immune cells but also has important metabolic functions which are not yet fully understood. Thus, we investigated the effect of CD26 in porcine parthenogenetic embryos. We attempted CD26 downregulation of porcine embryos by siRNA, and evaluated CD26 suppression of developmental competencies. Although the porcine embryos injected with CD26 siRNA were able to develop to the early stage, these embryos were decreased to form blastocysts. Our results indicated that CD26 is one of factors for the regulation of development of porcine embryos.

• Environmental Analysis Health and Toxicology
• /
• v.22 no.2 s.57
• /
• pp.165-170
• /
• 2007

Elevation of homocysteine levels is a risk factor for cardiovascular diseases and liver diseases. It has been reported that both streptozotocin-induced type I diabetic rats and obese type II diabetic rats have plasma total homocysteine lower than each control rats. We determined the effects of lean type II diabetes on homocysteine levels using type 2 diabetic Goto-Kakizaki rats. The concentrations of serum glucose were increased to ${\sim}two-fold$ of control levels and the total cholesterol levels were also increased in GK rats. Hepatic aspartate, histidine, threonine, alanine and methionine levels were significantly increased in GK rats. Plasma aspartate and glutamate levels were elevated, but threonine and arginine levels were decreased in GK rats. Plasma total homocysteine levels were not changed in GK rats, but hepatic total homocysteine levels were increased to ${\sim}three-fold$ of control levels. These results suggest that hepatic metabolism of sulfur-amino acid may be altered in diabetic condition.

• Journal of Nutrition and Health
• /
• v.30 no.2
• /
• pp.123-131
• /
• 1997

The influence of (-0-Hydroxycitrate(HCA), shown to be a competitive inhibitor of adenosine 5-triphosphate(ATP) citrate lyase, on food intake and body weight, serum triglyceride and cholosterol level, in vivo rates of fatty acid and cholesterol synthesis, and fat cell number and size was investigated. 3 groups of female, 5 weeks old Sprague Dawley rats, 8 animals each, were ad libitum meal-fed or pair-fed(3 hours from 10 : 00 to 13 : 00) AIN based high glucose diet for a total period of 8 weeks. Providing normolipidemic rats orally with 400mg of HCA formula containing approximately 20mg of HCA 1 hour prior to daily feeding schedule significantly depressed in vivo hepatic rates of fatty acid and cholesterol synthesis in the liver and adipose tissue. Serum triglyceride and cholesterol levels were significantly reduced by HCA. At the end of treatment period, the rats administered with HCA resulted in a significantly reduction in body weight gain. The reduction in weights was attributable to a significant decrease in fat cell size with a smaller extent, but not significant, reduction in fat cell number. Rats receiving HCA demonstrated less food intake than the controls ; however, this decreased caloric intake was not fully responsible for the HCA induced depression of hepatic and adipocytic lipogenesis, since experiment using pair-fed cojntrol rats showed, less magnitude but similar results. Both a anorectic and an antilipogenic properties of HCA seem to be responsible for this weight reduction activity of HCA. The outcome of this study suggest that metabolic regulation may be a feasible approach to the control of obesity and hyperlipidemia.

• Nutrition Research and Practice
• /
• v.7 no.5
• /
• pp.380-384
• /
• 2013

Zinc may participate in blood pressure regulation and in the pathogenesis of hypertension. The study examined the relationship between zinc status and blood pressure in obese Korean women. Forty obese women (body mass index (BMI) ${\geq}25kg/m^2$) aged 19-28 years participated in this study. Zinc intake was estimated from one 24 hour recall and 2-day diet records. Serum and urinary zinc concentrations were determined by atomic absorbance spectrophotometry. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using an automatic sphygmometer. Metabolic variables, such as waist circumference, triglyceride, high density lipoprotein (HDL) cholesterol, fasting glucose, and fasting insulin, were also measured. Dietary zinc intake of obese women was averagely 7.5 mg/day. Serum zinc and urinary zinc concentrations were $13.4{\mu}mol/L$ and $378.7{\mu}g/day$, respectively. Averages of SBP and DBP were 119 mmHg and 78 mmHg. Dietary zinc intake was negatively correlated with SBP after adjusting for energy intake (P < 0.05), but serum and urinary zinc concentrations were not found to be correlated with SBP or DBP. Multivariate linear regression analysis showed that dietary zinc intake was inversely associated with SBP in obese women after adjusting for body weight, energy intake and sodium intake (P = 0.0145). The results show that dietary zinc intake may be an independent risk factor of elevated SBP in obese Korean women.