Objective: Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. Methods: Herein, we constructed the high-fat diet-induced FLHS chicken model to investigate the genome-wide active enhancers and transcriptome by H3K27ac target chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-Seq) profiles of normal and FLHS liver tissues. Concurrently, an integrative analysis combining ChIP-seq with RNA-Seq and a comparative analysis with chicken FLHS, rat non-alcoholic fatty liver disease (NAFLD) and human NAFLD at the transcriptome level revealed the enhancer and super enhancer target genes and conservative genes involved in metabolic processes. Results: In total, 56 and 199 peak-genes were identified in upregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange) ≥1) (PP) and downregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange)≤-1) (PN), respectively; then we screened key regulatory targets mainly distributing in lipid metabolism (PCK1, APOA4, APOA1, INHBE) and apoptosis (KIT, NTRK2) together with MAPK and PPAR signaling pathway in FLHS. Intriguingly, PCK1 was also significantly covered in up-regulated super-enhancers (SEs), which further implied the vital role of PCK1 during the development of FLHS. Conclusion: Together, our studies have identified potential therapeutic biomarkers of PCK1 and elucidated novel insights into the pathogenesis of FLHS, especially for the epigenetic perspective.
Yeji Kang;Namhee Kim;Yunhwan Lee;Xiangxue An;Yoon-Sok Chung;Yoo Kyoung Park
Clinical Nutrition Research
/
v.12
no.3
/
pp.184-198
/
2023
Early prevention of sarcopenia can be an important strategy for muscle maintenance, but most studies target subjects at slightly pre-sarcopenic state. Our previous paper describes the effect of protein supplements rich in leucine and vitamin D on muscle condition, and in this paper, we performed a sub-analysis to evaluate who benefitted the most in terms of improvement in muscle health. A 12-week randomized clinical trial of 120 healthy adults (aged 50 to 80) assigned to an intervention group (n = 60) or control group (n = 60) were analyzed. Subjects in the intervention group received, twice per day, a protein supplement containing (per serving) 800 IU of vitamin D, 20 g of protein (3 g of total leucine), 300 mg of calcium, 1.1 g of fat, and 2.5 g of carbohydrate. The subjects were classified into 'insufficient' and 'sufficient' groups at 25-hydroxyvitamin D (25[OH]D) value of 30 ng/mL. The skeletal muscle mass index normalized to the square of the skeletal muscle mass (SMM) height (kg/m2) increased significantly in the 'insufficient group' difference value of change between weeks 0 and 12 (Δ1.07 ± 2.20; p = 0.037). The SMM normalized by body weight (kg/kg, %) was higher, but not significantly, in the insufficient group (Δ0.38 ± 0.69; p = 0.050). For people with insufficient (serum 25[OH]D), supplemental intake of protein and vitamin D, calcium, and leucine and adequate energy intake increases muscle mass in middle-aged and older adults and would be likely to exert a beneficial effect on muscle health.
Purpose: Korean patients with type 2 diabetes mellitus (T2DM) and obesity are at a high risk of developing severe non-alcoholic fatty liver disease (NAFLD). This study examined the dietary intakes and compared the risks of NAFLD-related complications in Korean patients with T2DM and obesity. Methods: Data from the Korean National Diabetes Program cohort were used to study patients with T2DM. Two hundred and sixty-five obese patients with T2DM (body mass index ≥ 25 kg/m2) were classified into NAFLD and non-NAFLD groups. The nutrient intake was analyzed using a 24-hour dietary recall questionnaire. Anthropometric and biochemical data were also obtained. Statistical analyses were performed to determine the significant differences between the 2 groups. Results: The serum gamma-glutamyl transpeptidase levels in obese patients with T2DM and NAFLD were significantly higher than in obese T2DM patients without NAFLD (p < 0.05). The serum glucose and lipid profiles showed no significant differences between the NAFLD and non-NAFLD groups. The carbohydrate, protein, and fat levels also did not differ significantly. The results showed that the fiber intake of the NAFLD and non-NAFLD groups was 14.11 ± 3.86 g/100 kcal and 15.70 ± 4.56 g/1,000 kcal, respectively, showing that the dietary fiber intake of the non-NAFLD group was significantly higher (p < 0.05). A correlation was observed between total fiber intake and γ-glutamyl transpeptidase in either patient group. In addition, the odds ratio of developing NAFLD was 0.29× lower when the fiber was consumed at 125% of adequate intake. Conclusions: A higher dietary fiber intake may reduce the risk of NAFLD in obese patients with T2DM. The dietary intake of Korean obese patients with T2DM should include and be enriched in dietary fiber to aid in preventing and treating NAFLD.
Objectives: This retrospective study attempted to determine whether the treatment effect improves as the longer the medication for obese patients, also, analyzed whether the long medication increases the burden on liver function. Methods: The subjects were 278 overweight and obese female patients who took the herbal medicine Jibangsayak (JBSY) for more than 15 days. The correlation between the duration of medication and the treatment effect was confirmed, and the correlation with the safety was also analyzed. Results: JBSY significantly reduced all obesity-related measures after treatment. All these valuables before treatment were not factors in determining the duration of medication. As the duration increased, the body mass index (BMI) improvement decreased and lean body and muscle mass increased. As the duration was closer to 60 days, BMI improvement increased, and in more than 90 days group, the BMI and body fat percentage improvement stagnated as the duration longer. Aspartate aminotransferase (AST), alanine aminotransferase, and gamma-glutamyl transferase decreased after treatment. Additionally, AST decreased as the duration increased. Conclusions: This result suggests that not only the high obesity-related measures at first visit not lengthen the duration of JBSY medication. And liver function levels did not worsen as the duration increased. This result is different from the general perception that the longer the duration of medication, the greater the burden on patient's drug metabolism. However, the fact that other factors that could affect liver function could not be excluded and that kidney function evaluation should have been performed simultaneously are limitations of this study and require more detailed research in the future.
A series of growing and digestion trials was conducted using Sprague- Dawley weanling male rats in order to determine the effects of two protein sources (casein and ISP (isolated soyprotein) ), three protein levels (10, 20 and 30%), and two feeding patterns (ad libitum and meal feeding) on the growth, protein and energy metabolism, and body composition of rats. The total energy level of experimental diets was kept constant in 3,600 kcal ME /kg diet. The results were as follows : 1) The amount of food intake and the weight gain of meal-fed group were lower than those of ad libitum group. Though the intake of meal-fed group on 20 and 30% casein diet was only 85% of ad libitum group, it was able to gain as much as ad libitum group. 2) There were no significant differences in the food efficiency ratio (FER) and the energy efficiency (weight gain per 100 kcal GE intake) between ad libitum and meal feeding group. The FER and the energy efficiency of 20 and 30% casein diets of meal-fed group were greater than those of ad libitum group. 3) Though the gross energy intake (GE ), the digestible energy (DE) and the metabolizable energy (ME) tended to be lower at meal-fed group, the DE/GE and the ME/GE ratios for meal-fed group were the same as those for ad libitum. 4) Though meal- fed group fed less amount of nitrogen than ad libitum group, there were no differences in nitrogen balance and the retention of rats among the treatments. Actually meal-fed group retained more nitrogen than ad libitum group at the levels of 20 and 30% dietary protein. 5) After growing and digestion trials, the body composition of rats was constant among all treatments. Significantly high negative correlation coefficient (r = -0.77) was found between the body fat content and the body moisture content. Consequently, this study suggests that meal- fed group on 20 and 30% casein diets has shown more effective utilization of the ingested food and energy than ad libitum group, and increasing tendency of weight gain and the body fat deposition. Those influences of meal feeding pattern in rats were more effective on the casein diet than on the ISP diet.
This study was carried out to investigate the effects of different sources and level of dietary lipid on lecithin : cholesterol acyltrasferase activity and cholesterol metabolism in male rats of Sprague-Dawley strain. The effects of different lipid sources was compared with sardine oil($\omega$3 EPA and DHA), beef tallow(SFA), perilla oil($\omega$3 linolenic acid) and corn oil($\omega$6 linoleic acid). Diets were formulated in such a way that 10%, 20% and 40% dietary energy were supplied with each of four experimental lipid sources. Control diet contained only non-lipid energy. A total number of 78 rats, equally divided into 13 groups, were fed the experimental diets for a period of 6 weeks. In vitro cultures were also carried out to study the cholesterol synthetic activity in the liver prepared from rats used in feeding trials. The concentration of plasma total cholesterol, HDL-cholesterol, LDL-cholesterol and HDL-C/T/C(total cholesterol) ratio were significantly (p<0.001) influenced by dietary lipid sources. Higher HDL-cholesterol and lower LDL-cholesterol concentration in plasma were obtained in rats fed $\omega$3 fatty acid supplemented diets(sardine oil and perilla oil group) compared to diets containing $\omega$6 and saturated fatty acid(corn oil and beef tallow group). In total cholesterol concentration of plasma, beef tallow group was significantly (p<0.001) higher than other lipid groups, and non-lipid group was significantly(p<0.05) higher than the lipid supplemented groups. The activity of lecithin : cholesterol acyltransferase(LCAT) in plasma was greatly(p<0.001) affected by dietary lipid sources and levels. In LCAT acivity of plasma, lipid supplemented groups were significantly(p<0.05) higher than non-lipid group, vegetable oil groups were significantly (p<0.001) higher than animal fat groups, and sardine oil group were significalylty (p<0.001) higher than beef tallow group. Also perilla oil group was significanlty (p<0.05) higher than corn oil group, and sardine oil group was significantly (p<0.05) higher than perilla oil group. Low lipid group, compared with medium or high lipid group, showed higher activity of LCAT in plasma. In cholesterol synthetic activity of liver tissues culture, sardine oil group($\omega$3 EPA and DHA) was significantly(p<0.001) higher than other lipid groups, non-lipid group was significantly(p<0.001) higher than the lipid supplemented groups, and amimal fat group were significantly(p<0.001) higher than vegetable oil groups, but the synthetic activity was not affected by dietary lipid levels.
Lee, Hyejin;Kim, Jinhee;Park, Jun Yeon;Kang, Ki Sung;Park, Joeng Hill;Hwang, Gwi Seo
Journal of Ginseng Research
/
v.41
no.3
/
pp.257-267
/
2017
Background: Heat-processed ginseng, sun ginseng (SG), has been reported to have improved therapeutic properties compared with raw forms, such as increased antidiabetic, anti-inflammatory, and antihyperglycemic effects. The aim of this study was to investigate the antiobesity effects of SG through the suppression of cell differentiation and proliferation of mouse 3T3-L1 preadipocyte cells and the lipid accumulation in Caenorhabditis elegans. Methods: To investigate the effect of SG on adipocyte differentiation, levels of stained intracellular lipid droplets were quantified by measuring the oil red O signal in the lipid extracts of cells on differentiation Day 7. To study the effect of SG on fat accumulation in C. elegans, L4 stage worms were cultured on an Escherichia coli OP50 diet supplemented with $10{\mu}g/mL$ of SG, followed by Nile red staining. To determine the effect of SG on gene expression of lipid and glucose metabolism-regulation molecules, messenger RNA (mRNA) levels of genes were analyzed by real-time reverse transcription-polymerase chain reaction analysis. In addition, the phosphorylation of Akt was examined by Western blotting. Results: SG suppressed the differentiation of 3T3-L1 cells stimulated by a mixture of 3-isobutyl-1-methylxanthine, dexamethasone, and insulin (MDI), and inhibited the proliferation of adipocytes during differentiation. Treatment of C. elegans with SG showed reductions in lipid accumulation by Nile red staining, thus directly demonstrating an antiobesity effect for SG. Furthermore, SG treatment down-regulated mRNA and protein expression levels of peroxisome proliferator-activated receptor subtype ${\gamma}$ ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein-alpha ($C/EBP{\alpha}$) and decreased the mRNA level of sterol regulatory element-binding protein 1c in MDI-treated adipocytes in a dose-dependent manner. In differentiated 3T3-L1 cells, mRNA expression levels of lipid metabolism-regulating factors, such as amplifying mouse fatty acid-binding protein 2, leptin, lipoprotein lipase, fatty acid transporter protein 1, fatty acid synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase, were increased, whereas that of the lipolytic enzyme carnitine palmitoyltransferase-1 was decreased. Our data demonstrate that SG inversely regulated the expression of these genes in differentiated adipocytes. SG induced increases in the mRNA expression of glycolytic enzymes such as glucokinase and pyruvate kinase, and a decrease in the mRNA level of the glycogenic enzyme phosphoenol pyruvate carboxylase. In addition, mRNA levels of the glucose transporters GLUT1, GLUT4, and insulin receptor substrate-1 were elevated by MDI stimulation, whereas SG dose-dependently inhibited the expression of these genes in differentiated adipocytes. SG also inhibited the phosphorylation of Akt (Ser473) at an early phase of MDI stimulation. Intracellular nitric oxide (NO) production and endothelial nitric oxide synthase mRNA levels were markedly decreased by MDI stimulation and recovered by SG treatment of adipocytes. Conclusion: Our results suggest that SG effectively inhibits adipocyte proliferation and differentiation through the downregulation of $PPAR{\gamma}$ and $C/EBP{\alpha}$, by suppressing Akt (Ser473) phosphorylation and enhancing NO production. These results provide strong evidence to support the development of SG for antiobesity treatment.
Park, Surk-Hoon;Jang, Mi-Jin;Hong, Jung-Hee;Rhee, Soon-Jae;Choi, Kyung-Ho;Park, Mo-Ra
Journal of the Korean Society of Food Science and Nutrition
/
v.36
no.1
/
pp.43-50
/
2007
This study was to investigate the effect of mulberry leaf water extract on lipid metabolism of rats fed high cholesterol diets. Sprague-Dawley male rats were randomly assigned to two normal groups; mulberry extract-free (N), 0.16% mulberry leaf extract (NM) groups and high cholesterol groups with four different levels of mulberry leaf extract; 0% (HC), 0.08% (HCL), 0.16% (HCM), and 0.32% mulberry leaf extract (HCH) groups. Serum levels of triglyceride, cholesterol, LDL-cholesterol and AI index in mulberry leaf extract supplemented groups were significantly lower than the HC group (p<0.05). The level of HDL-cholesterol in the HC group was significantly (p<0.05) reduced, compared with N group, but it was increased by mulberry leaf extract supplementation. Mulberry leaf extract had no effect on the UDP-glucuronyl transferase activity. Also, there was no significant difference in the level of liver cholesterol between the HC and mulberry leaf extract supplemented groups, while there was significant difference in the levels of liver total lipid and triglyceride. The HCM and HCH groups had more significant reduction in the activity of lipoprotein lipase in epididymal fat tissue than the HC group. The levels of total lipid, triglyceride and total cholesterol in epididymal fat tissue of HCL, HCM and HCH groups were decreased compared to HC group. The levels of total lipid, triglyceride and total cholesterol in feces from HCL, HCM and HCH groups were higher than those of HC group.
The purpose of this study was to investigate the effect of H$_2$O fraction of Dioscorea japonica Thunb (DJT) with vitamin E on blood glucose and fat metabolism in streptozotocin (STZ) diabetic rats. Sprague-Dawley rats (200∼230 g) weighing were divided into five groups; the normal group, the STZ-control group, the DJT group, the DJT-vitamin E group and the vitamin E group. Diabetes was induced in the male rats by injection of STZ into tail vein at a dose of 45 mg/kg body weight. The H$_2$O fraction of DR (500 mg/kg) and 10 mg/kg of vitamin E (㎗-${\alpha}$-tocopherol) given orally were administered for 14 days. The body weight was monitored and levels of hematocrit, protein and glucose were determined. The plasma concentrations of cholesterol; triglyceride, free fatty acid and HDL-cholesterol were measured. The activities of aminotranseferase were analysed. The body weight gain was shown no significantly higher in the normal group than all STZ groups. The administration of H$_2$O fraction of DJT and vitamin E showed a significant increase in plasma protein concentrations. The all STZ group was formed to be effective in decreasing blood glucose levels. Plasma insulin concentrations were highered in diabetic rats fed on H$_2$O fraction of DJT. Plasma triglyceride and free fatty acid levels were lower in the vitamin E group than the STZ-control group. The plasma cholesterol levels of all STZ groups were not significantly different and HDL-cholesterol levels were increased in all STZ groups fed on H$_2$O fraction of DJT and vitamin E, specially in the DJT-vit. E group. The all STZ group does not significantly change aminotransferase activity of diabetic rats. These results indicated that DJT was a potential candidate for a treatment of diabetes which can enhance insulin activity The effect of vitamin E on insulin activity will be examined in more detail.
Sixteen ruminally cannulated Korean native steers (Hanwoo; $626.2\pm47.72$ kg) were used to investigate the effects of polyclonal antibodies against abdominal (AAb) and subcutaneous adipocyte membrane proteins (SAb) on ruminal fermentation patterns and blood metabolites. The body weight (BW) of Hanwoo was decreased 2-weeks after AAb and SAb injection, BW reduction was also observed in control and non-immunized serum groups, indicating that stress induced by other factors (e.g. blood sampling etc.) rather than antibodies injection may affect the BW reduction. Antibodies treatment did not affect (P > 0.05) rumen pH, volatile fatty acids and ammonia-N concentration. The ranges were similar with typical ranges of those in Hanwoo. Compared with control, blood urea N concentration was decreased in AAb group and increased (P < 0.05) in SAb group before antibodies treatment. However, none of the groups were significantly (P > 0.05) affected at 2- or 4-weeks after the treatment. Concentration of plasma glucose in the non-immunized serum group was significantly higher (P < 0.05) than the other groups at 0-week after treatment. However, antibodies treatment did not affect the concentration of plasma glucose. Concentration of plasma triglyceride showed no difference (P > 0.05) between the groups and ranged from 11.4 to 19.9 mg/dl, which is the perfect range of plasma triglyceride of Hanwoo fed concentrate based diets. In conclusion, these results may indicate that the present AAb and SAb have safety in nutritional physiological metabolism in Hanwoo. Further study on in vivo fat reduction of the antibodies against abdominal and subcutaneous adipocytes PMPs of Hanwoo is required for inedible fat-reduced high quality beef production.
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