• Journal of Life Science
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• v.30 no.7
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• pp.640-650
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• 2020

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF protein family which is highly synthesized in the liver, pancreas, and adipose tissue. Depending on the expression tissue, FGF21 uses endo- or paracrine features to regulate several metabolic pathways including glucose metabolism and energy homeostasis. Different physiologically stressful conditions such as starvation, a ketogenic diet, extreme cold, and mitochondrial dysfunction are known to induce FGF21 synthesis in various tissues to exert either adaptive or defensive mechanisms. More specifically, peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor alpha control FGF21 expression in adipose tissue and liver, respectively. In addition, the pharmacologic administration of FGF21 has been reported to decrease the body weight and improve the insulin sensitivity and lipoprotein profiles of obese mice and type 2 diabetes patients meaning that FGF21 has attracted huge interest as a therapeutic agent for type 2 diabetes, obesity, and non-alcoholic fatty liver disease. However, understanding FGF21 remains complicated due to the paradoxical condition of its tissue-dependent expression. For example, nutrient deprivation largely increases hepatic FGF21 levels whereas adipose tissue-derived FGF21 is increased under feeding condition. This review discusses the issues of interest that have arisen from existing publications, including the tissue-specific function of FGF21 and its action mechanism. We also summarize the current stage of a clinical trial using several FGF21 analogs.

• BMB Reports
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• v.55 no.12
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• pp.609-614
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• 2022

Mutation of the gene for adenomatous polyposis coli (APC), as seen in Apc^Min/+ mice, leads to intestinal adenomas and carcinomas via stabilization of β-catenin. Transmembrane 4 L six family member 5 (TM4SF5) is involved in the development of non-alcoholic fatty liver disease, fibrosis, and cancer. However, the functional linkage between TM4SF5 and APC or β-catenin has not been investigated for pathological outcomes. After interbreeding Apc^Min/+ with TM4SF5-overexpressing transgenic (Tg^TM4SF5) mice, we explored pathological outcomes in the intestines and livers of the offspring. The intestines of 26-week-old dual-transgenic mice (Apc^Min/+:Tg^TM4SF5) had intramucosal adenocarcinomas beyond the single-crypt adenomas in Apc^Min/+ mice. Additional TM4SF5 overexpression increased the stabilization of β-catenin via reduced glycogen synthase kinase 3β (GSK3β) phosphorylation on Ser9. Additionally, the livers of the dualtransgenic mice showed distinct sinusoidal dilatation and features of hepatic portal hypertension associated with fibrosis, more than did the relatively normal livers in Apc^Min/+ mice. Interestingly, TM4SF5 overexpression in the liver was positively linked to increased GSK3β phosphorylation (opposite to that seen in the colon), β-catenin level, and extracellular matrix (ECM) protein expression, indicating fibrotic phenotypes. Consistent with these results, 78-week-old Tg^TM4SF5 mice similarly had sinusoidal dilatation, immune cell infiltration, and fibrosis. Altogether, systemic overexpression of TM4SF5 aggravates pathological abnormalities in both the colon and the liver.

• Journal of Animal Science and Technology
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• v.63 no.4
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• pp.934-953
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• 2021

Ciglitazone is a member of the thiazolidinedione family, and specifically binds to peroxisome proliferator-activated receptor-γ (PPARγ), thereby promoting adipocyte differentiation. We hypothesized that ciglitazone as a PPARγ ligand in the absence of an adipocyte differentiation cocktail would increase adiponectin and adipogenic gene expression in bovine satellite cells (BSC). Muscle-derived BSCs were isolated from six, 18-month-old Yanbian Yellow Cattle. The BSC were cultured for 96 h in differentiation medium containing 5 µM ciglitazone (CL), 10 µM ciglitazone (CM), or 20 µM ciglitazone (CH). Control (CON) BSC were cultured only in a differentiation medium (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 (Pax7) proteins was confirmed in the BSC by immunofluorescence staining. The CL, CM, and CH treatments produced higher concentrations of triacylglycerol and lipid droplet accumulation in myotubes than those of the CON treatment. Ciglitazone treatments significantly increased the relative expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, fatty acid synthase, stearoyl-CoA desaturase, and perilipin 2. Ciglitazone treatments increased gene expression of Pax3 and Pax7 and decreased expression of myogenic differentiation-1, myogenin, myogenic regulatory factor-5, and myogenin-4 (p < 0.01). Adiponectin concentration caused by ciglitazone treatments was significantly greater than CON (p < 0.01). RNA sequencing showed that 281 differentially expressed genes (DEGs) were found in the treatments of ciglitazone. DEGs gene ontology (GO) analysis showed that the top 10 GO enrichment significantly changed the biological processes such as protein trimerization, negative regulation of cell proliferation, adipocytes differentiation, and cellular response to external stimulus. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DEGs were involved in the p53 signaling pathway, PPAR signaling pathway, biosynthesis of amino acids, tumor necrosis factor signaling pathway, non-alcoholic fatty liver disease, PI3K-Akt signaling pathway, and Wnt signaling pathway. These results indicate that ciglitazone acts as PPARγ agonist, effectively increases the adiponectin concentration and adipogenic gene expression, and stimulates the conversion of BSC to adipocyte-like cells in the absence of adipocyte differentiation cocktail.

• Journal of Nutrition and Health
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• v.46 no.4
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• pp.307-314
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• 2013

Resveratrol (RSV) exerts several beneficial effects on metabolism and metaflammation-related diseases, including diabetes and non-alcoholic fatty liver disease (NAFLD). The purpose of this study is to investigate whether RSV affects pathophysiology of diabetes and NAFLD as well as hepatic autophagy in a rodent model of diet induced obesity (DIO). DIO was induced in a subset of C57BL/6J mice fed a high fat (HF, 45% kcal fat) diet. After six weeks of HF diet treatment, RSV (8 mg/kg/day) was administered via an osmotic pump for a period of four weeks. Therefore, the experimental groups were as follows: 1) lean control (CON), 2) HF diet-induced obese control (HF), and 3) HF_RSV. Body weight and food intake were monitored daily. Fasting glucose, insulin, and adiponectin in serum and lipid profiles in serum and liver were analyzed. In addition, the autophagic process was investigated using transmission electron microscopy (TEM). Body weight and food intake were not affected by RSV treatment. Impaired glucose control accompanied by DIO was recovered with RSV as shown by lower levels of fasting serum glucose and insulin when compared with HF obese controls. In addition, RSV treatment resulted in increased levels of serum adiponectin, however, indices of lipid profile in serum and livers were reduced. Results of TEM analysis showed that a HF diet induced excessive autophagy with the presence of double-membrane autophagosomes, which was ameliorated by RSV. The regulatory effect of RSV on autophagy was confirmed by the altered LC3-II formation, which increased with a HF diet and was decreased by RSV treatment. These results suggest that RSV treatment improves glucose control and lipid profile and these beneficial effects may be mediated by an altered autophagic process.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.4
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• pp.374-381
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• 2017

The LAP (lipid accumulation product) index is an indicator of excessive fat accumulation in combination with the fasting triglyceride concentration and waist circumference. This study examined the relationship between the LAP index and ALT (alanine aminotransferase) level and the effect of the LAP index on the ALT level. Cross-sectional studies were conducted on healthy adult males without a history of liver disease. From January 2015 to June 2017, 13,854 adults between 20 and 70 years of age, who underwent health screening at a general hospital in Gyeonggi-do, were enrolled in this study. The LAP index was calculated as [waist circumference (cm)-65]${\times}$[triglyceride (mmol/L)] for males. Serum ALT abnormalities were set at 40 IU/L or more in males. All subjects underwent measurements of the anthropometric indicators and physiological examinations. A significant increase in ALT with increasing LAP quintiles was observed (p<0.001). The LAP index correlated with ALT (r=0.238, p<0.001). Insulin (r=0.449, p<0.001) and HDL-cholesterol (r=-0.369, p<0.001) were strongly correlated with LAP. In addition, the LAP index is a factor affecting the ALT level (p<0.001). As the LAP index increased, the risk of an elevated ALT was higher (p<0.001). In conclusion, the LAP index was a predictor of an ALT elevation in Korean men.

• Korean Journal of Food Science and Technology
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• v.49 no.6
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• pp.676-684
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• 2017

The present study aimed to examine the hepatoprotective effects of ethanol extracts from steam-dried ginseng berry (SGBE) in both $\text\tiny{D}$-Galactosamine/Lipopolysaccharide ($\text\tiny{D}$-GalN/LPS)-sensitized mice and in vitro models. Our results clearly demonstrated that SGBE significantly reduced the level of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase in blood, and $TNF{\alpha}$ was normalized in 8 h after the treatment with $\text\tiny{D}$-GalN/LPS. Coincidently, major organs remained unimpaired when compared to $\text\tiny{D}$-GalN/LPS control group. Moreover, p38, which stimulates expression of NAFLD-associated cytokines, was markedly inhibited when treated with SGBE. In vitro analysis revealed that the main components of SGBE, linoleic acid and ginsenoside Re/Rd, may play a role in protecting liver from $\text\tiny{D}$-GalN/LPS-induced toxicity. Finally, we concluded that SGBE may be a promising therapeutic agent for preventing damage to the liver.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.2
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• pp.207-214
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• 2009

Purpose: Childhood obesity can be complicated by hypertension, hyperlipidemia, non-alcoholic fatty liver disease, and diabetes mellitus. The aim of this study was to evaluate the prevalence of obesity and metabolic complications of children and adolescents based on the degree of obesity. Methods: We analyzed the records of 8,880 students who received student health examinations between May 2006 and October 2008 at the Eulji General Hospital. The prevalence of obesity was evaluated by the body mass index and obesity index. A total of 1,076 obese students had blood tests. We analyzed aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting glucose, total cholesterol, and blood pressure according to the degree of obesity. Results: According to the body mass index, the overall prevalence of obesity was 7.2% (7.8% of male and 6.5% of female students). Based on the obesity index, 12.3% of students (mild: 6.3%, moderate: 5.0%, and severe: 1.0%) were obese. The prevalence of hypercholesterolemia, ALT elevation, and hypertension were increased as a function of the degree of obesity (p<0.05), but hyperglycemia showed no significant differences (p=0.298). The overall prevalence of ALT elevation was 17.7% (mild obese group, 10.4%; moderate obese group, 20.5%; and severe obese group, 46.8%). The prevalence of hypercholesterolemia, hypertension, and hyperglycemia were significantly higher in the elevated ALT group (24.7%, 42.6%, and 5.2%, respectively) compared to the normal ALT group (11.1%, 29.8%, and 2.0%, respectively; p<0.05). Conclusion: Hypercholesterolemia, liver function test abnormalities, and hypertension were associated with the degree of obesity. We should focus our attention on managing obese children and adolescents to prevent metabolic complications.

• Korean Journal of Plant Resources
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• v.29 no.1
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• pp.1-10
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• 2016

Obesity is a pro-inflammatory state that contributes to the development of metabolic disorders such as hyperlipidemia, insulin resistance, type 2 diabetes, non-alcoholic fatty liver, and cardiovascular disease. In this study, we evaluated the inhibition of adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice by Peucedanum japonicum Thunberg L. water extract (PJT). Lipid accumulation measurement indicates that PJT markedly inhibited adipogenesis in a dose-dependent manner. RT-PCR results demonstrated that the mRNA expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α (C/EBPα) in 3T3-L1 cells were significantly down-regulated by PJT treatment. Oral administration of PJT (100, 300, and 500 ㎎/㎏, b.w/daily for 4 weeks) was conducted in high-fat diet induced obese mice and C57BL/6 mice. The PJT-administered group of HFD-induced mice had a lower body weight gain, along with decreased serum levels of glucose, triglycerides, and total cholesterol compared with the control mice, however, the HDL-cholesterol/total cholesterol ratio was increased. Furthermore, the elevated mRNA expression levels of adipogenesis related genes in the white adipose tissue of obese mice were significantly suppressed by PJT. These results indicate that PJT exhibits anti-obesity effects in obese mice by decreasing in serum lipid levels and lipogenesis related gene.