• Journal of Life Science
• /
• v.30 no.6
• /
• pp.542-549
• /
• 2020

A previous study reported that Ulmus macrocarpa Hance water extract (UME) can improve hyperlipid metabolism and the involvement of suppressed lipid synthesis through adenosine monophosphate-activated protein kinase (AMPK) pathway regulation was suggested. Further exploration of the lipid metabolism between liver and peripheral tissue was necessary to confirm that work, and so this study aimed to extend the possibility that UME can regulate serum lipids. After a 6-week in vivo trial of oral administration of UME to rats with induced hyperlipidemia, serum levels of triglyceride (TG) and total cholesterol (TC) were seen to decrease while HDL cholesterol increased. The UME administrations also decreased the TC and TG levels from the control in liver analysis. However, the suggestion that UME regulates the AMPK pathway to improve hyperlipid states through the suppression of hepatic lipogenesis seems to be only one part of the extract's effect. Indeed, serum concentrations of apolipoproteins A and B were returned to baseline levels of the control group in response to UME administration whilst the liver lipid content was much reduced; this cannot occur through the suggested suppression of hepatic lipogenesis alone. Therefore, a possible mechanism of UME could be that it improves blood circulation by modulating serum lipid levels through both the prior stimulation of lipid oxidation and the suppression of hepatic lipogenesis.

• The Journal of Internal Korean Medicine
• /
• v.19 no.1
• /
• pp.22-38
• /
• 1998

This study was to investigate the hepatoprotective and anticirrhotic effects of Ganyeumilhobang(GIE) on the acute and chronic liver injury induced by various agents. Chronic liver injury induced by dimethylnitrosamine(DMN) ; a new experimental model for cirrhosis and the intraperitoneal injection of dimethylnitrosamine in the rat. Acute liver njury induced by carbon tetrachloride$(CCl_4)$ and D-galactosamine ; a experimental model for acute liver injury, the administration of $CCl_4$ and the intraperitoneal injection of D-galactosamine in the rat. The development of fibrosis and acute liver injury by the three prescriptions were examined by the chemical analysis of AST, ALT, prothrombin time and hydroxyproline. The results obtained were as follows. 1. The increasing level of hydroxyproline volume induced by DMN in mice was decreased by the oral administration of GIB. 2. The degree of histological fibrosis and hepatic inflammatory cell infiltration induced by $CCl_4$ decreased by the oral administration of GIB. 3. The increase of senun AST and ALT of mice with acute liver damage induced by $CCl_4$ and D-galactosamine was inhibited by the administration of GIB. 4. The prolongation of prothrombin time(seconds) of mice acute liver damage induced by $CCl_4$ was shortened by the oral administration of GIB. 5. The liver of mice was hepatectomized partial1y after the oral administration of GIB. The mitotic index(% of nuclei), weight of liver, contents of protein, RNA and DNA synthesis of the liver tissue were increased by the oral administration of GIB.

• Journal of Ginseng Research
• /
• v.47 no.3
• /
• pp.420-428
• /
• 2023

Background: Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. Methods: HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. Results: Cell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. Conclusion: Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

• The Korean Journal of Pharmacology
• /
• v.11 no.1 s.17
• /
• pp.47-53
• /
• 1975

The metabolism of many drugs and also of steroid hormones is mediated by enzymes located in the microsomal fraction in smooth surfaced endoplasmic reticulum of mammalian liver. The duration and intensity of action of many drugs are largely determined by the speed at which they are metabolized in the body. Repeated administration of phenobarbital results in the induction of enzymes that metabolize a number of drugs. Lee et al. reported that daily administration of phenobarbital in rats significantly increased the activities of amylase in the pancreatobiliary juice, but the concentration of cholate in the bile was significantly lower in the treated group than that in the control group. After animals were treated with $CCl_4$, histological changes were shown in the endoplasmic reticulum, decreased microsomal enzyme activity and decreased hepatic protein synthesis were apparent. The purpose of the present report was to study the interaction between a 'microsomal-stimulating' agent such as phenobarbital and a 'microsomal- depressing' agent such as $CCl_4$ on hepatic and pancreatic functions in rats. The results obtained are summarized as follows: 1. The mortality rate of $CCl_4$ treated group was 34% and was decreased this figure to 15% with phenobarbital pretreatment. 2. In animals treated with phenobarbital the volume of biliary-pancreatic secretion was markedly elevated but the volume was decreased significantly in animals treated with $CCl_4$. 3. Total bilirubin output was elevated markedly in the $CCl_4$ treated group of rats pretreated with phenobarbital. The bilirubin concentration was increased in $CCl_4$ treated group and decreased in the group treated phenobarbital alone. 4. The concentration and total output of cholate in the bile were significantly lower in the all experimental group than control group. 5. In the animals treated with phenobarbital alone and phenobarbital plus $CCl_4$, the activity of lipase in pancreatobiliary juice was elevated, while in the animals treated with $CCl_4$ alone no change was observed. 6. The activity of amylase in the pancreatobiliary juice was decreased in the $CCl_4$ treated group, but elevated markedly in phenobarbital group and also elevated in phenobarbital-$CCl_4$ group. By the above results, it is concluded, when the liver was damaged by $CCl_4$, the exocrine function of pancreas and liver was decreased simultaneously. However, in the animals pretreated with phenobarbital, the toxicity of $CCl_4$ on the liver and pancreas was reduced.

• Journal of Nutrition and Health
• /
• v.55 no.4
• /
• pp.462-475
• /
• 2022

Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.

• BMB Reports
• /
• v.42 no.4
• /
• pp.232-237
• /
• 2009

Sterol regulatory element-binding protein (SREBP)-1c plays a crucial role in the regulation of lipogenic enzymes in the liver. We previously reported that an X-chromosome-linked RNA binding motif (RBMX) regulates the promoter activity of Srebp-1c. However, still unknown was how it regulates the gene expression. To elucidate this mechanism, we screened the cDNA library from mouse liver by yeast two-hybrid assay using RBMX as bait and identified scaffold attachment factor B1 (SAFB1). Immunoprecipitation assay demonstrated binding of SAFB1 to RBMX. Chromatin immunoprecipitation assay showed binding of both SAFB1 and RBMX to the upstream region of Srebp-1c gene. RNA interference of Safb1 reduced the basal and RBMX-induced Srebp-1c promoter activities, resulting in reduced Srebp-1c gene expression. The effect of SAFB1 overexpression on Srebp-1c promoter was found only in the presence of RBMX. These results indicate a major role for SAFB1 in the activation of Srebp-1c through its interaction with RBMX.

• Journal of Life Science
• /
• v.20 no.7
• /
• pp.1019-1026
• /
• 2010

Obesity and being overweight are strongly associated with the development of metabolic disease such as diabetes, hypertension, dyslipidemia. High-fat diet (HFD) is one of the most important factors which cause obesity. In this study, C57BL/6 mice were treated with a HFD for 22 weeks in order to induce obesity and hyperglycemia. Twenty-two weeks later, body weight and plasma glucose level of the HFD group were significantly increased, compared with the normal diet (ND) group. Intra-peritoneal glucose tolerance test (IPGTT) showed glucose intolerance in the HFD group compared with the ND group. These results confirmed that a HFD induced obesity and hyperglycemia in C57BL/6 mice. Plasma levels of triglyceride (TG) and total cholesterol (TC) were increased in the HFD group compared with the ND group. Hepatic levels of TG and TC were also increased by a HFD. To investigate the alteration of lipid metabolism in liver, proteins which are related to lipid metabolism were observed. Among lipid synthesis related enzymes, fatty acid synthase (FAS) and glycerol phosphate acyl transferase (GPAT) were significantly increased in the HFD group. Apolipoprotein B (apoB) and microsomal triglyceride transport protein (MTP), which are related to lipid transport, were significantly increased in the HFD group. Interestingly, protein level and phosphorylation of AMP-activated protein kinase (AMPK), which is known as a metabolic regulator, were significantly increased in the HFD group compared with the ND group. In the present study we suggest that HFD may physiologically increase the proteins which are related with lipid synthesis and lipid transport, but that HFD may paradoxically induce the activation of AMPK.

• Korean Journal of Fisheries and Aquatic Sciences
• /
• v.19 no.1
• /
• pp.83-91
• /
• 1986

The activity of the liver cells of greenling, Agrammus agrammus were histologically investigated under photo-and electron microscopy, and studied by comparing seasonal changes of hepatosomatic index (HSI). The materials were monthly collected at the costal area of Tongbaeksom, Pusan, Korea, from September 1983 to August 1984. The annual variations of HSI of male were not distinct, but those of HSI in female began to increase in autumn, and reached the maximum in winter when the ovary was getting mature. During the period of yolk accumulation in the oocytes, the female liver and its hepatic cells were seen to large and nuclei and nucleoli were hypertrophic also. At this time the amounts of glycogen and lipid in the cells gradually decreased, while basophilic substance (RNA) increased. And well-developed granular endoplasmic reticula binding ribosomes were supposed to play the leading role in protein synthesis and deposition for vitellogenin in the cystoplasm. Just prior to spawning, glycogen and lipid droplets were decreased, but basophilic substances(RNA) were found in a high concentration especially at the peripheral region of the liver cells of females. In the liver cells of males, were hardly altered by gonadal maturation, basophilic substances gradually increased, glycogen particles and lipid droplets were still observed in large quantities. After spawning, basophilic subtances decreased in the liver cells of female and male.

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

• Development and Reproduction
• /
• v.10 no.2
• /
• pp.97-103
• /
• 2006

Vitellogenin(Vg) is a sex specific serum protein present in sexually maturing female blood of oviparous vertebrates. Estrogen($E_2$) is a main inducer of hepatic Vg synthesis. We investigated the effects of androgen and growth hormone(GH) on regulation of Vg and estrogen receptor(ER) genes in Japanese eel. Immature eels($200{\sim}250\;g$) were given a single injection of $E_2(5{\sim}5,000\;{\mu}g/kg\;bw)$ alone, or in combination with eel recombinant GH(eGH, $1{\sim}10\;{\mu}g/kg$) or methyltestosterone(MT, $1{\sim}5\;mg/kg$) and sacrificed 10 days after the hormone treatments. Expression levels of ER and Vg genes from the liver were determined by means of reverse transcription and polymerase chain reaction(RT-PCR). Administration of $E_2$ stimulated Vg gene expression in a dose dependent manner. Levels of Vg mRNA after the injection of $E_2(500\;{\mu}g/kg)$ with MT(5mg/kg) or eGH($10\;{\mu}g/kg$) were much higher than in that of $E_2$ alone($500\;{\mu}g/kg$). Whereas, injection of either vehicle, eGH ($10\;{\mu}g/kg$) or MT(5mg/kg) alone did not induce the expression of Vg gene in the liver. ER mRNA was detected from the fish treated with vehicle alone. $E_2$ injection($5{\sim}500\;{\mu}g/kg\;bw$) increased this ER expression but dose dependent response was not clear. Addition of MT(5mg/kg) or eGH($10\;{\mu}g/kg$) did not affect $E_2-stimulated$ ER mRNA expression. This study confirms the necessity of $E_2$ as the primary factor for Vg gene expression and requirement of additional hormones such as MT or GH for the full expression of Vg mRNA, and suggests that the additive effect of MT or GH on Vg gene expression would be mediated by some unknown factors other than ER.