Changes in peripheral inflammation-related gene expression by postprandial glycemic response in healthy Japanese men.

OBJECTIVES: Continuous postprandial hyperglycemia is associated with the onset of cardiovascular disease. In recent years, the mRNA expression of inflammation-related genes in peripheral blood leukocytes has been shown to be induced by an increase in blood glucose levels. The aim of this study was to investigate differences in the expression of inflammation-related genes in peripheral blood leukocytes in response to an increase in blood glucose from individuals who consumed two kinds of breakfast meals with different glycemic indexes (GIs). METHODS: Twenty healthy Japanese men 40 to 70 y of age were given low- or high-GI meals for breakfast for 14 d. Clinical examinations were performed on days 7 and 14. Their blood glucose levels and insulin concentrations were measured from before breakfast ingestion to 120 min after. Additionally, using the blood obtained before and 120 min after breakfast, the mRNA expression levels of inflammation-related genes in peripheral leukocytes were measured. RESULTS: The blood glucose levels were significantly lower in the low-GI meal intake group at 30, 60, and 120 min after breakfast than in the high-GI meal intake group. The intake of high-GI meals for 6 d led to an increase in the mRNA levels of interleukin-1ß, S100A4, and CD18 compared with the period of low-GI meals. CONCLUSION: The intake of a low-GI breakfast for 1 wk in healthy Japanese men resulted in lower postprandial blood glucose and insulin levels, which were accompanied by a reduced expression of inflammation-related genes in peripheral blood leukocytes.

Regulation of hepatic genes related to lipid metabolism and antioxidant enzymes by sodium butyrate supplementation.

BACKGROUND: Rapid influx of energy caused by fasting/refeeding repeatedly enhances fatty acid synthesis leading to triacylglycerol accumulation and production of reactive oxygen species (ROS), increasing the risk of non-alcoholic steatohepatitis (NASH). Previous studies have reported that the ingestion of butyrate is effective at preventing hepatic disorders, which are accompanied by fat accumulation and inflammation. The aim of this study is to reveal the mechanism of action of butyrate, and thus we investigated the effects of dietary butyrate on the expressions of antioxidant enzymes in the livers of rats during refeeding following fasting. METHODS: Thirty-seven male rats were divided into six groups (6-7 animals per group): non-fasting, fasting, refeeding with a high sucrose diet as control for 12 or 24 h, and refeeding with a high sucrose diet containing 5% sodium butyrate (NaB) for 12 or 24 h. All groups except the non-fasting group were fasted for 72 h before refeeding. Statistical analysis was conducted among 4 refeeding groups (refeeding with the control diet for 12 or 24 h, and refeeding with a diet containing NaB for 12 or 24 h). RESULTS: Supplementation with NaB significantly reduced (p < 0.05) fatty acid synthase (Fas) gene expression and increased the expression of the carnitine palmitoyltransferase 1α (Cpt1a) gene, resulting in reduced triacylglycerol content in the livers of rats refed the NaB diet compared with controls at 24 h after the start of refeeding. The mRNA levels of the genes related to glutathione synthesis were significantly higher (p < 0.05) in the livers of the butyrate group than the control group. In addition, the mRNA level of Foxo3a, a transcription factor that regulates the expressions of antioxidant enzymes, was higher in the butyrate group than controls. The acetylation levels of histone H4 around the Foxo3a gene tended to be increased (p = 0.055) by refeeding with the NaB diet. CONCLUSION: NaB supplementation in the diet for refeeding reduced the rate of lipid synthesis and stimulated fatty acid oxidation in the liver, which inhibited fat accumulation and the risk of NASH. The transcriptional regulation of Foxo3a involves histone acetylation around the gene.

Glucose and TNF enhance expression of TNF and IL1B, and histone H3 acetylation and K4/K36 methylation, in juvenile macrophage cells.

Hyperglycemia activates innate leukocytes such as monocytes and induces pro-inflammatory cytokine expression, resulting in increased monocyte adhesion to aortic endothelial cells. In this study, we investigated whether high glucose and/or tumor necrosis factor (TNF) would enhance pro-inflammatory cytokine expression of tumor necrosis factor (TNF) and interleukin (IL)-1ß (IL1B) by altering histone modifications in U937, a juvenile macrophage cell line. The mRNA levels of TNF and IL1B in U937 cells were significantly affected by glucose concentration and TNF treatment. Mono-methylated histone H3K4 signals around TNF and IL1B were lower in cells treated with high glucose compared with low glucose. Conversely, tri-methylated histone H3K4 and H3K36 signals were higher in cells treated with high glucose compared with low glucose. TNF treatment of U937 cells cultured in high glucose enhanced histone H3K36 tri-methylation, particularly around the gene regions of TNF and IL1B. Histone acetylation was induced by treatment with TNF in high-glucose medium. The induction of acetylation and tri-methylation of K4 and K36 of histone H3 around TNF and IL1B by treatment with high glucose and/or TNF was positively associated with the induction of these genes in juvenile macrophage U937 cells.

Sustained effects of resistant starch on the expression of genes related to carbohydrate digestion/absorption in the small intestine.

Resistant starch (RS) consumption has beneficial effects on health, such as reduced postprandial blood glucose levels. In this study, we evaluated the effect of a 14-day diet containing RS on α-glucosidase activity and the expression of genes related to carbohydrate digestion/absorption in rats. We examined whether the effects of RS persist when the rats were shifted to a control diet. The results suggest that RS consumption reduces α-glucosidase activity and Mgam, Si and Sglt1 mRNA levels in the proximal jejunum. In addition, RS consumption appeared to influence the serum GIP level, up to 2 days after the animals were shifted to a control diet. To our knowledge, this is the first report that RS has a sustained effect on gut hormone expression and the expression of genes related to carbohydrate digestion/absorption in the proximal jejunum.

Glucose and TNF enhance expression of TNF and IL1B, and histone H3 acetylation and K4/K36 methylation, in juvenile macrophage cells.

Hyperglycemia activates innate leukocytes such as monocytes and induces pro-inflammatory cytokine expression, resulting in increased monocyte adhesion to aortic endothelial cells. In this study, we investigated whether high glucose and/or tumor necrosis factor (TNF) would enhance pro-inflammatory cytokine expression of tumor necrosis factor (TNF) and interleukin (IL)-1ß (IL1B) by altering histone modifications in U937, a juvenile macrophage cell line. The mRNA levels of TNF and IL1B in U937 cells were significantly affected by glucose concentration and TNF treatment. Mono-methylated histone H3K4 signals around TNF and IL1B were lower in cells treated with high glucose compared with low glucose. Conversely, tri-methylated histone H3K4 and H3K36 signals were higher in cells treated with high glucose compared with low glucose. TNF treatment of U937 cells cultured in high glucose enhanced histone H3K36 tri-methylation, particularly around the gene regions of TNF and IL1B. Histone acetylation was induced by treatment with TNF in high-glucose medium. The induction of acetylation and tri-methylation of K4 and K36 of histone H3 around TNF and IL1B by treatment with high glucose and/or TNF was positively associated with the induction of these genes in juvenile macrophage U937 cells.

Undernutrition in Pregnant Rats Induces Glucose Intolerance with Enhanced Expression of Inflammation-Related Genes in Peripheral Leukocytes of the Offspring.

Impaired glucose tolerance (IGT) induces chronic inflammation and subsequent development of complications triggered by arteriosclerosis. Moreover, undernutrition in pregnant rodents can induce IGT in their offspring. Here, we assessed whether undernutrition in pregnant rats would induce chronic inflammation in their offspring by measuring the expression levels of inflammation-related genes in peripheral blood leukocytes. Pregnant Wistar rats were divided into two groups: the control group received an American Institute of Nutrition Rodent diet (AIN-93G) ad libitum, and the undernutrition group had their diet restricted by 50% (w/w) compared with the control group from day 10 of pregnancy until birth of the offspring. Subsequently, mothers and pups were allowed to access the AIN-93G diet freely. At day 35 after birth, male pups were fasted for 4 h and subsequently orally administered with glucose solution (2 g/kg body weight). Blood glucose area under the curve (AUC) after glucose loading was significantly greater in the undernutrition group than the control group. The mRNA levels for inflammatory cytokines were increased by glucose loading especially in the undernutrition group. Expressions of genes encoding S100A9 and cell adhesion molecule CD11b were increased by glucose loading in the undernutrition group. Thus, undernutrition of pregnant rats during mid to late gestation induced the expression of inflammation-related genes in peripheral blood leukocytes of their offspring, with the development of IGT and impaired insulin secretion.

Molecular Regulations of Mucosal Maltase Expressions.

Two major α-glucosidase (maltase) genes, sucrase-isomaltase (SI) and maltase-glucoamylase (MGAM), respectively, are expressed in the small intestine. In this review, we have summarized whether jejunal expression of these maltase genes is regulated by dietary manipulations, which may affect carbohydrate availability from the luminal side, through changes in the binding of transcription factors and/or histone code on these genes. Studies using a model of mice fed either a low-starch or a high-starch diet for 7 days, found the mRNA levels of SI, MGAM, and Na-glucose cotransporter (SGLT1) genes in the jejunum to be increased in parallel by feeding a high-starch diet. Chromatin immunoprecipitation assays, using jejunal tissue of mice and rats fed a high-starch diet, revealed that the diet increased the acetylations of histones H3 and H4, bindings of coactivators, including general control of amino acid synthesis (GCN5) and the transcriptional factors, including caudal-related homeobox 2 (CDX2), and hepatocyte nuclear factor 1 (HNF1), not only in the promoter/enhancer regions, but also in the transcribed regions of SI and MGAM genes. Feeding rats a diet rich in resistant starch led to a concomitant reduction of mRNA levels of the MGAM gene and histone H3 modifications (acetylations and di-/tri-methylations) in the jejunum. These data suggest that a signal elicited by available glucose in the jejunal mucosa is associated with SI and MGAM gene expressions through a histone code, such as acetylation and di-/tri-methylations of histone H3 in the promoter/enhancer and transcribed regions of SI and MGAM genes.

Regulation of the circadian rhythmic expression of Sglt1 in the mouse small intestine through histone acetylation and the mRNA elongation factor, BRD4-P-TEFb.

Jejunal sodium/glucose co-transporter (Sglt1) displays circadian expression. The jejunum was collected every 4 h from mice, and we examined histone acetylation and binding of bromodomain-containing protein-4 (BRD4) around of the gene. Histone acetylation increased in the transcribed region of Sglt1 prior to induction of the gene. Furthermore, the binding of mRNA elongation factor around the gene showed circadian rhythm.

Insulin-induced inhibition of gluconeogenesis genes, including glutamic pyruvic transaminase 2, is associated with reduced histone acetylation in a human liver cell line.

OBJECTIVES: Hepatic glutamic pyruvic transaminase (GPT; also known as alanine aminotransferase) is a gluconeogenesis enzyme that catalyzes conversions between alanine and pyruvic acid. It is also used as a blood biomarker for hepatic damage. In this study, we investigated whether insulin regulates GPT expression, as it does for other gluconeogenesis genes, and if this involves the epigenetic modification of histone acetylation. METHODS: Human liver-derived HepG2 cells were cultured with 0.5-100nM insulin for 8h, and the mRNA expression of GPT, glutamic-oxaloacetic transaminase (GOT), γ-glutamyltransferase (GGT), PCK1, G6PC and FBP1 was measured. We also investigated the extent of histone acetylation around these genes. RESULTS: Insulin suppressed the mRNA expression of gluconeogenesis genes (GPT2, GOT1, GOT2, GGT1, GGT2, G6PC, and PCK1) in HepG2 cells in a dose-dependent manner. mRNA levels of GPT2, but not GPT1, were decreased by insulin. Histone acetylation was also reduced around GPT2, G6PC, and PCK1 in response to insulin. CONCLUSION: The expression of GPT2 and other gluconeogenesis genes such as G6PC and PCK1 was suppressed by insulin, in association with decreases in histone H3 and H4 acetylation surrounding these genes.

Relationship between epigenetic regulation, dietary habits, and the developmental origins of health and disease theory.

Environmental stressors during developmental stages are hypothesized to increase the risk of developing metabolic diseases such as obesity, type 2 diabetes, hypertension, and psychiatric diseases during later life. This theory is known as the Developmental Origins of Health and Disease (DOHaD). Recent studies suggest that accumulation of environmental stress, including those during developmental stages, is internalized as acquired information designated as "epigenetic memory." This epigenetic memory is generally indicated as DNA methylation and histone modifications in the chromatin. In general, the demethylation of CpG islands induces histone acetylation and associated changes from heterochromatin to euchromatin, and enhances transcriptional activation. These changes are induced by the binding of transcriptional factors to cis-elements located on promoter and enhancer regions and the associated binding of histone acetyl-transferase and the transcription initiation complex. Recent studies have demonstrated novel epigenetic modifications that regulate transcription elongation steps by activating histone acetylation and bromodomain-containing protein 4, which contains two bromodomains to bind acetylated histones, on the gene body (transcribed region). Gene expression alterations induced by carbohydrate signals and by changes in energy balance in the body are regulated by this model. In addition, induction of many metabolic genes, which are induced or reduced in adulthood by malnutrition during developmental stages, by intake of major nutrients, or development of lifestyle diseases in adulthood, are targeted by these novel epigenetic changes. In the present review, we introduce epigenetic regulations and the relationship with nutrient intake, and discuss links between epigenetic regulation and the development of metabolic diseases according to DOHaD.

BRD4 regulates fructose-inducible lipid accumulation-related genes in the mouse liver.

OBJECTIVE: Fructose intake induces hepatic steatosis by activating fat synthesis. In this study, we searched for genes that showed acute induction in the livers of mice force-fed with fructose, and examined how this induction is regulated. MATERIALS/METHODS: We identified genes induced at 6h after the fructose force-feeding using a microarray and quantitative real-time RT-PCR. Histone acetylation and an acetylated histone binding protein bromodomain containing (BRD)4 binding around the fructose-inducible genes were examined using a chromatin immunoprecipitation assay. We examined whether (+)-JQ1, an inhibitor of the binding between the BRD4 and acetylated histones, inhibited the expressions of fructose-inducible genes, histone acetylation and BRD4 binding around the genes. RESULTS: We identified upregulated genes related to lipid accumulation, such as Cyp8b1, Dak and Plin5, in mice force-fed with fructose compared with those force-fed with glucose. Acetylation of histones H3 and H4, and BRD4 binding around the transcribed region of those fructose-inducible genes, were enhanced by fructose force-feeding. Meanwhile, (+)-JQ1 treatment reduced expressions of fructose-inducible genes, histone acetylation and BRD4 binding around these genes. CONCLUSIONS: Acute induction of genes related to lipid accumulation in the livers of mice force-fed with fructose is associated with the induction of histone acetylation and BRD4 binding around these genes.

Fasting during the suckling-weaning transient period of rats induces inflammatory gene expression in the adipose tissue and peripheral leukocytes.

OBJECTIVE: Nutritional deficiency during developmental stages could be associated with subsequent development of inflammation-related metabolic abnormalities. In this study, we examined the effects of a 3-d fast during the suckling-weaning transient period of rats, and subsequent intake of high-fat-high-sucrose (HF) and low-fat-high-starch (LF) diets in adulthood, on the expression of inflammatory genes in adipose tissue and peripheral leukocytes. METHODS: Male Sprague-Dawley rats were deprived of food for 3 d during the suckling-weaning transient period, and were subsequently fed an HF or LF diet for 14 wk from 17 wk of age. Serum monocyte chemoattractant protein-1 (MCP-1) concentration and mRNA levels of inflammatory genes in mesenteric adipose tissues were assessed at 31 wk of age. The mRNA levels of inflammatory genes at 0 h and 2 h after oral glucose load at 30 wk of age in peripheral leukocytes were measured. RESULTS: Fasting induced circulating MCP-1 protein in rats fed an LF diet but not an HF diet. The HF diet induced high mRNA levels of tumor necrosis factor-α, interleukin-1ß, and S100 proteins in peripheral leukocytes at 2 h after glucose load in fasted rats when compared with controls. Expression of CD11c, an activated macrophage marker, was induced in the fasted group given an HF diet during adulthood. CONCLUSIONS: Fasting rats during the suckling-weaning transient period and an HF diet intake during adulthood enhance inflammation by promoting the expression of inflammatory genes in adipose tissue and peripheral leukocytes.

Loss of circadian rhythm of circulating insulin concentration induced by high-fat diet intake is associated with disrupted rhythmic expression of circadian clock genes in the liver.

OBJECTIVE: Peripheral clock genes show a circadian rhythm is correlated with the timing of feeding in peripheral tissues. It was reported that these clock genes are strongly regulated by insulin action and that a high-fat diet (HFD) intake in C57BL/6J mice for 21days induced insulin secretion during the dark phase and reduced the circadian rhythm of clock genes. In this study, we examined the circadian expression patterns of these clock genes in insulin-resistant animal models with excess secretion of insulin during the day. MATERIALS/METHODS: We examined whether insulin resistance induced by a HFD intake for 80days altered blood parameters (glucose and insulin concentrations) and expression of mRNA and proteins encoded by clock and functional genes in the liver using male ICR mice. RESULTS: Serum insulin concentrations were continuously higher during the day in mice fed a HFD than control mice. Expression of lipogenesis-related genes (Fas and Accß) and the transcription factor Chrebp peaked at zeitgeber time (ZT)24 in the liver of control mice. A HFD intake reduced the expression of these genes at ZT24 and disrupted the circadian rhythm. Expression of Bmal1 and Clock, transcription factors that compose the core feedback loop, showed circadian variation and were synchronously associated with Fas gene expression in control mice, but not in those fed a HFD. CONCLUSIONS: These results indicate that the disruption of the circadian rhythm of insulin secretion by HFD intake is closely associated with the disappearance of circadian expression of lipogenic and clock genes in the liver of mice.

Fasting for 3 days during the suckling-weaning transient period in male rats induces metabolic abnormalities in the liver and is associated with impaired glucose tolerance in adulthood.

PURPOSE: Recent studies suggest that nutritional status during developmental periods is associated with subsequent development of metabolic abnormalities. In this study, we examined whether malnutrition by fasting for 3 days during the suckling-weaning transient period induces subsequent development of metabolic abnormalities in rats. METHODS: Male Sprague-Dawley rats were fasted for 3 days during the suckling-weaning transient period. They are subsequently fed a high-fat, high-sucrose (HF) or low-fat, high-starch (LF) diet for 14 weeks from 17 weeks of age, and the liver and blood samples were collected for measuring mRNA and protein levels of metabolic genes and blood concentrations of glucose and insulin, respectively. RESULTS: Fasting for 3 days during the suckling-weaning transient period induced impaired glucose tolerance in rats fed the LF diet in adulthood. Liver triglycerides in rats fed the HF diet in adulthood increased to 140 % in rats fasted for 3 days during the suckling-weaning transient period compared with those non-fasted. Furthermore, liver expression of FBP1 and ACCα genes in adult rats fed the LF diet increased to 125 and 145 %, respectively, in rats fasted for 3 days during the suckling-weaning transient period compared to non-fasted rats. PEPCK1 protein expression levels in rats fed the LF diet were higher in rats fasted for 3 days during the suckling-weaning transient period than in non-fasted rats. CONCLUSION: Fasting for 3 days in rats during the suckling-weaning transient period enhances metabolic abnormalities in animals fed a HF or LF diet in adulthood by confounding metabolism of lipid and sugar in the liver.

Serum Fatty Acid Binding Protein 4 Concentrations Are Positively and Independently Associated with Blood Pressure and Abdominal Fat among Parameters in Health Check-Ups in Ordinary Middle-Aged Japanese Males.

We wished to examine potential associations among blood concentrations of fatty acid-binding protein (FABP) 4 and parameters in health check-ups such as abdominal fat area (AFA) and blood pressure (BP) in middle-aged Japanese males. We conducted a cross-sectional study of males who participated in health check-ups in Japan. We excluded participants diagnosed with metabolic diseases by the time of their check-up. A total of 305 subjects (30-64 [mean±standard deviation, 47.3±8.5] y) were recruited. Areas of total-abdominal, visceral and subcutaneous fat were measured using computed tomography. We compared the association of serum concentrations of FABP4 with various clinical parameters by Pearson product-moment correlation coefficient (PPMCC) analyses, and by step-wise multivariate linear regression analyses (MLRA). PPMCC analyses showed that blood concentrations of FABP4 were positively associated with: body mass index; areas of fat (total abdominal, visceral, subcutaneous); systolic BP; diastolic BP; total cholesterol; low-density lipoprotein-cholesterol; triacylglycerol; activities of γ-glutamyl transpeptidase, aspartate aminotransferase and alanine aminotransferase; white blood cell count; and levels of creatinine. Step-wise MLRA showed that AFAs (visceral and subcutaneous) and diastolic BP were positively and independently associated with serum concentrations of FABP4 among the parameters tested. These data suggest that serum concentrations of FABP4 are independently and positively associated with BP and AFA among parameters measured in health check-ups in middle-aged Japanese males.

Induction of histone H3K4 methylation at the promoter, enhancer, and transcribed regions of the Si and Sglt1 genes in rat jejunum in response to a high-starch/low-fat diet.

OBJECTIVE: Histone methylation patterns are associated with various aspects of biology, including transcriptional regulation. Methylation of histone H3 at lysine 4 (H3K4) leads to transcriptional activation through recruitment of transcription activation complexes onto target genes; in contrast, methylation of histone H3K9, or histone H4K20, leads to transcriptional inactivation attracting heterochromatin protein 1 (HP1). It is not yet known whether jejunal induction of sucrase-isomaltase (Si) and sodium-dependent glucose cotransporter (Sglt1) genes by intake of a high-starch/low-fat diet in rats is regulated by coordinated changes of these histone methylation events. In the present study, we investigated whether these histone modifications at the promoter, enhancer, and transcribed regions of Si and Sglt1 genes in rat jejunum are affected by consumption of a high-starch/low-fat diet. METHODS: Chromatin immunoprecipitation assays using antibodies against methylated-histone H3K4, H3K9, H4K20, and HP1 were performed at various regions associated with the Si and Sglt1 genes in jejunum of rats fed a high-starch/low-fat diet or a low-starch/high-fat diet for 7 d. RESULTS: Feeding rats the high-starch/low-fat diet induced mono-, di-, and trimethylation of histone H3K4 on the promoter and transcribed regions of the Si and Sglt1 genes. In contrast, methylation of histones H3K9 and H4K20, and binding of HP1 at these gene regions, were not affected by the high-starch/low-fat diet. CONCLUSION: These observations suggest that induction of Si and Sglt1 gene expression in rat jejunum by a high-starch/low-fat diet intake is positively associated with histone H3K4 methylation, but not with histone H3K9/H4K20 methylation, or with binding of HP1.

Re-feeding rats a high-sucrose diet after 3 days of starvation enhances histone H3 acetylation in transcribed region and expression of jejunal GLUT5 gene.

Fasting for 3 days leads to reduction in the expression of GLUT5 and SGLT1 genes in jejunum. Re-feeding a high-sucrose diet in fasted rats enhanced mRNA levels and histone H3 acetylation on transcribed region of GLUT5 gene within 24 h, but not in SGLT1. Responsiveness of jejunal GLUT5 gene is associated with changes in histone H3 acetylation on transcribed region.

Induction by fructose force-feeding of histone H3 and H4 acetylation at their lysine residues around the Slc2a5 gene and its expression in mice.

It has been reported that fructose force-feeding rapidly induced jejunal Slc2a5 gene expression in rodents. We demonstrate in this study that acetylation at lysine (K) 9 of histone H3 and acetylation at K5 and K16 of histone H4 were more enhanced in the promoter/enhancer to transcribed regions of the Slc2a5 gene in fructose force-fed mice than in glucose force-fed mice. However, fructose force-feeding did not induce acetylation at K14 of histone H3, or at K8 and K12 of histone H4 around the Slc2a5 gene. These results suggest that fructose force-feeding induced selective histone acetylation, particularly of H3 and H4, around the jejunal Slc2a5 gene in mice.

The regulation of jejunal induction of the maltase-glucoamylase gene by a high-starch/low-fat diet in mice.

Maltase and glucoamylase are derived from the same mRNA and are responsible for digestion of starch in the small intestine. Their jejunal activities in rodents are induced by a high-starch/low-fat (HS)-diet. However, it is unknown whether jejunal expression of the maltase-glucoamylase (Mgam) gene is enhanced by the HS-diet. In this study, we found that jejunal Mgam mRNA was increased by a HS-diet in mice. We showed that the HS-diet increased acetylation of histones, bindings of a coactivator, Creb binding protein (CREBBP), and the transcriptional factors caudal type homeobox 2 (CDX2) and HNF1 homeobox (HNF1) in the promoter/enhancer and transcriptional regions of Mgam gene. This suggests that the increase in the jejunal activity of maltase and glucoamylase caused by a HS-diet in mice is regulated at the mRNA level through histone acetylation and binding of CREBBP, CDX2 and HNF1 in the promoter/enhancer and transcriptional regions of Mgam gene.

Inductions of histone H3 acetylation at lysine 9 on SGLT1 gene and its expression by feeding mice a high carbohydrate/fat ratio diet.

OBJECTIVE: We examined in this study whether histone H3 acetylations on jejunal NA(+)/glucose transport-1 (SGLT1) gene are associated with induction of its gene by feeding mice a high carbohydrate/fat ratio diet. METHODS: The chromatin immunoprecipitation (ChIP) assays using antibodies of acetylated histone H3 were performed in jejunum of mice fed a high carbohydrate/fat ratio diet or a low carbohydrate/fat ratio for 7 d. RESULTS: The acetylations of histone H3 of lysine 9/14 were highly detected on the SGLT1 gene and the levels were enhanced by feeding mice a high carbohydrate/fat ratio diet. Histone H3 acetylation at lysine 9 was enhanced by feeding a high carbohydrate/fat ratio diet, whereas that at lysine 14 was not enhanced significantly. CONCLUSION: These observations indicate that induction of SGLT1 gene expression by feeding a high carbohydrate/fat ratio diet is associated with acetylation of histone H3 at lysine 9 on the SGLT1 gene.