• Asian-Australasian Journal of Animal Sciences
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• 제25권9호
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• pp.1300-1308
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• 2012

The 5'-adenosine monophosphate-activated protein kinase (AMPK) is a key part of a kinase-signaling cascade that acts to maintain energy homeostasis. The objective of this experiment was to investigate the possible effects of fasting and refeeding on the gene expression of hypothalamic AMPK, some appetitive regulating peptides and lipid metabolism related enzymes. Seven-day-old male broiler (Arbor Acres) chicks were allocated into three equal treatments: fed ad libitum (control); fasted for 24 h; fasted for 24 h and then refed for 24 h. Compared with the control, the hypothalamic gene expression of $AMPK{\alpha}2$, $AMPK{\beta}1$, $AMPK{\beta}2$, $AMPK{\gamma}1$, Ste20-related adaptor protein ${\beta}$ ($STRAD{\beta}$), mouse protein $25{\alpha}$ ($MO25{\alpha}$) and agouti-related peptide (AgRP) were increased after fasting for 24 h. No significant difference among treatments was observed in mRNA levels of $AMPK{\alpha}1$, $AMPK{\gamma}2$, LKB1 and neuropeptide Y (NPY). However, the expression of $MO25{\beta}$, pro-opiomelanocortin (POMC), corticotropin-releasing hormone (CRH), ghrelin, fatty acid synthase (FAS), acetyl-CoA carboxylase ${\alpha}$ ($ACC{\alpha}$), carnitine palmitoyltransferase 1 (CPT-1) and sterol regulatory element binding protein-1 (SREBP-1) were significantly decreased. The present results indicated that 24 h fasting altered gene expression of AMPK subunits, appetite regulation peptides and lipometabolism related factors in chick's hypothalamus; the hypothalamic FAS signaling pathway might be involved in the AMPK regulated energy homeostasis and/or appetite regulation in poultry.

• The Korean Journal of Physiology and Pharmacology
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• 제14권1호
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• pp.1-9
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• 2010

AMP-activated protein kinase (AMPK) protects various tissues and cells from ischemic insults and is activated by many stimuli including mechanical stretch. Therefore, this study investigated if the activation of AMPK is involved in stretch-induced cardioprotection (SIC). Intraventricular balloon and aorto-caval shunt (ACS) were used to stretch rat hearts ex vivo and in vivo, respectively. Stretch preconditioning reduced myocardial infarct induced by ischemia-reperfusion (I/R) and improved post-ischemic functional recovery. Phosphorylation of AMPK and its downstream substrate, acetyl-CoA carboxylase (ACC) were increased by mechanical stretch and ACC phosphorylation was completely blocked by the AMPK inhibitor, Compound C. AMPK activator (AICAR) mimicked SIC. Gadolinium, a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of AMPK and ACC, whereas diltiazem, a specific L-type calcium channel blocker, did not affect AMPK activation. Furthermore, SIC was abrogated by Compound C and gadolinium. The in vivo stretch induced by ACS increased AMPK activation and reduced myocardial infarct. These findings indicate that stretch preconditioning can induce the cardioprotection against I/R injury, and activation of AMPK plays an important role in SIC, which might be mediated by SACs.

• 대한한방내과학회지
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• 제35권1호
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• pp.70-78
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• 2014

Objectives : Hoechunyanggyeok-san (HYS) is a traditional herbal medicine, which has been clinically used for treating febrile and inflammatory diseases. HYS has been reported to be a useful treatment for diabetes, atherosclerosis and hyperlipidemia in the type 1 diabetic model. However, the mechanism of the effects of HYS against hyperglycemia and hyperlipidemia is poorly understood. In the present study, we investigated the underlying mechanism of ameliorative effect of HYS on hyperglycemia and hyperlipidemia in vivo. Methods : HYS (10, 50 mg/kg/day, p.o.) was administered every day for 2 weeks to db/db mice and its effect was compared with vehicle-treated db/db mice. To confirm serum glucose and triglyceride (TG) changes, serological testing was performed. The levels of sterol regulatory element-binding protein-1 (SREBP-1) activity and Sirtuin1 (SIRT1), AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase ${\alpha}$ ($ACC{\alpha}$) expression were analyzed by western blot analysis. Results : The administration of HYS significantly decreased the elevated serum glucose and TG in db/db mice. HYS administration increased the levels of SIRT1 and AMPK expression compared with the vehicle-treated group. Moreover, HYS treatment significantly inhibited SREBP-1 activity and $ACC{\alpha}$ expression in the liver, while the vehicle-treated group exhibited their increase. Conclusions : In conclusion, HYS is suggested to have an improvement effect on hyperglycemia and hyperlipidemia by activating the SIRT1/AMPK signaling pathway and inhibiting SREBP-1.

• The Korean Journal of Physiology and Pharmacology
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• 제22권1호
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• pp.23-33
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• 2018

Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis through GR acetylation in experimental CS.

• Journal of Ginseng Research
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• 제32권3호
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• pp.187-193
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• 2008

The present study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice. The db/db mice were divided into three groups: diabetic control group (DC), Korean red ginseng group (KRG, 100 mg/kg) and metformin group (MET, 300 mg/kg), and treated with drugs once per day for 10 weeks. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in KRG-, 67.7% in MET-treated group. With decreased plasma glucose and insulin levels, the insulin resistance index of the KRG-treated group was reduced by 27.6% compared to the DC group. The HbA1c levels in KRG and MET-treated groups were also decreased by 11.0% and 18.9% compared to that of DC group, respectively. Plasma triglyceride and non-esterified fatty acid levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the KRG-treated group compared to those in DC group. Histological analyses of the liver and fat tissue of mice treated with KRG revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the DC group. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin contents, but decreased glucagon production. To elucidate action mechanism of KRG, effects on AMP-activated protein kinase (AMPK) and its downstream target proteins responsible for fatty acid oxidation and gluconeogenesis were explored in the liver. KRG activated AMPK and acetyl-coA carboxylase (ACC) phosphorylations, resulting in stimulation of fatty acid oxidation. KRG also caused to down regulation of SREBP1a and its target gene expressions such as FAS, SCD1 and GPAT. In summary, our results suggest that KRG exerted the anti-diabetic effect through AMPK activation in the liver of db/db mice.

• Journal of Animal Science and Technology
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• 제62권6호
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• pp.854-863
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• 2020

This study was aimed to investigate the inhibitory effects of Porphyra dentata (P. dentata) extract on the adipogenesis of 3T3-L1 cells and evaluate its anti-obesity effect. The proliferation of 3T3-L1 cells and differentiation of adipocytes under treatment of P. dentata extract was examined by measuring the cell viability using alamarBlue assay and lipid droplets by Oil Red O staining. Results showed that P. dentata extract has no cytotoxicity effect and lipid droplets formation decreased in a concentration-dependent manner in 3T3-L1 cells. It has been confirmed that transcription factors affecting lipid accumulation and anti-adipogenic effects during cell differentiation are linked to P. dentata extract. We observed that P. dentata shows lowering the mRNA expression of peroxisome proliferator-activated receptor γ2 (PPARγ2), CCAAT/enhancer binding protein α (C/EBPα) that adipogenesis-associated key transcription factors and inhibiting adipogenesis in the early stages of differentiation. Treating the cells with P. dentata did not only suppressed PPARγ2 and C/EBPα but also significantly decreased the mRNA expression of adiponectin, Leptin, fatty acid synthase, adipocyte protein 2, and Acetyl-coA carboxylase 1. Overall, the P. dentata extract demonstrated inhibitory property in adipogenesis, which has a potential effect in anti-obesity in 3T3-L1 cells.

• 대한본초학회지
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• 제37권5호
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• pp.17-26
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• 2022

Objective : The aim of the present study is to examine hepatic lipid-lowering and anti-inflammatory effects of silymarin combined with Jakyakgamcho-tang on non-alcoholic fatty liver disease in a high fat diet-induced obese mice model. Methods : C57BL/6 mice were divided into four dietary groups: (1) Normal, (2) Control (60% high-fat diet), (3) Control + silymarin 50 mg/kg/day (Silymarin), (4) Control + Silymarin 50 mg/kg/day + Jakyakgamcho-tang 100 mg/kg/day (SPG). After 12 weeks administration, mice were sacrificed and lipids and inflammation-related biomarkers were analyzed liver and plasma. Results : Silymarin and SPG treatments significantly lowered body and liver weights compared to the Control. Serumlipids (triglyceride (TG), total cholesterol) and pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin 1𝛽, and IL-6) concentrations were significantly lowered in the Silymarin and SPG groups than the Control group. Silymarin and SPG treatments suppressed hepatic TG level and hepatic lipid droplets compared to the Control. Theses two treatments significantly increased hepatic kinase B1 and AMP-activated protein kinase protein levels, and significantly decreased hepatic key lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase and stearyl coenzyme A desaturase 1) protein levels than the Control. SPG also significantly increased hepatic fatty acid oxidation-related protein (peroxisome proliferator-activated receptor alpha and uncoupling protein 2) levels than the Control. Conclusions: Silymarin and SPG suppressed hepatic lipid accumulation by regulating hepatic protein expression, and lowered blood pro-inflammatory cytokines concentrations though the synergic effect of silymarin and Jakyakgamchotang was not clear.

• 대한융합한의학회지
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• 제5권1호
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• pp.55-60
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• 2023

Objectives: This study was performed to investigate the effect of TJGB on the liver of high-fat diet (HFD)-fed mice and the cell viability of HepG2 cells. Methods: After a week adaptation, 8-week-old C57BL/6N mice were fed with a 45% HFD or normal diet for 3 weeks. For the next 9 weeks, the mice were divided into 6 groups: normal diet group; HFD group; HFD plus orlistat group; HFD plus Ephedra sinica Stapf (ES) group; HFD plus low dose of TJGB group; HFD plus high dose of TJGB group. To estimate the effect of TJGB in the liver of HFD-fed mice, the protein expressions of phospho-acetyl-CoA carboxylase (p-ACC) and liver X Receptor (LXR) were determined by Western blot assay. The cell viability of ES and TJG was also evaluated in HepG2 cells. Results: The administration of TJGB had little effect on the protein expressions of p-ACC and LXR in the liver of HFD-fed mice. And the cytotoxicity was showed above 7.8 ㎍/mL in HepG2 cells. Conclusion: Further research is needed to evaluate the mechanism of TJGB on hepatic steatosis and cytotoxicity in HepG2 cells.

• Journal of Animal Science and Technology
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• 제54권5호
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• pp.369-373
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• 2012

AMP-activated protein kinase (AMPK)는 체내 에너지 수준을 감지하고 당과 지방의 대사를 조절하는 인자로 밝혀졌다. 이러한 에너지 센서로서 AMPK의 역할은 심혈관계 및 비만과 당뇨 등의 대사성 질환에 밀접한 관계가 있다. 영양적 관점에서 AMPK는 지방산의 합성 및 분해를 통해 간에서 지방대사 조절에 중요한 역할을 한다. 특히 근육의 경우 glucose 흡수를 관장하며, 근육세포 내 glucose의 유입을 증가 시킨다. 하지만, AMPK의 활성이 대사기질의 흡수와 이용에 미치는 영향에 대한 정확한 기전은 아직까지 불분명하다. 또한 영양적 수준 차이에 따른 AMPK의 활성이 단백질 합성에 미치는 영향은 아직 보고된 바 없다. 따라서 본 연구의 목적은 C2C12 myotube에서 AMPK 활성물로 알려진 5-aminoimidazole-4-carbozamide-1-${\beta}$-D-ribonucleoside (AICAR)가 glucose 농도차이에 따른 AMPK 활성과 단백질함량에 미치는 영향을 알아보기 위함이다. 배양된 C2C12 근육세포에서 AICAR는 glucose의 함량에 관계없이 AMPK를 활성화 시켰다. 단백질 농도는 낮은 수준 (LG)에 비해 높은 수준의 glucose (HG)가 처리된 myotube에서 증가되었고, AICAR에 의해 그 효과는 더욱 증대 되었다. C2C12 myotube에서 HG 처리는 AMPK와 acetyl CoA carboxylase (ACC)의 인산화에 영향을 주지 않았지만, LG의 처리로 인해 AMPK와 ACC의 인산화가 증가되었다 (p<0.05). 또한, AICAR (2mM)의 처리는 glucose의 수준과는 관계없이 AMPK와 ACC의 인산화를 증가시켰다. 총 단백질 수준은 HG 처리에 의해 증가 되었고, 이는 AICAR의 처리에 의해서 더 높게 증가되었다. Proteasome 활성은 HG 처리구에서 LG에 비해 7.5% 낮게 나타났고, AICAR 처리는 proteasome 활성을 LG와 HG 처리구에서 각각 63%와 54% 감소 시켰다. Glucose의 수준은 mTOR의 인산화 수준에 영향을 주지 않았다. 하지만, AICAR는 LG 처리구에서 만 mTOR의 인산화 수준을 유의적으로 증가시켰고, HG 처리구에는 mTOR에 영향을 주지 않았다. 따라서, glucose 처리는 단백질을 proteasome으로부터 보호 하거나, glucose가 AMPK의 단백질 합성 저해 기능을 방해하여 세포내 단백질 합성을 중가 시키는 것으로 사료 된다. 결론적으로, 영양적 수준에 의해 AMPK 활성 및 단백질 합성과 분해가 조절된다는 것을 의미한다.

• Asian-Australasian Journal of Animal Sciences
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• 제14권3호
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• pp.333-337
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• 2001

This study investigated the effects of fermented product from Bacillus subtilis (FPBS) on feed conversion efficiency, fat accumulation and ammonia production in broiler chicks. Sixty female broilers (strain Chunky, 7-day old) were divided into four groups and raised in individual cages. One group was fed a commercial diet without supplementation of FPBS as the control and the other three groups were fed commercial diets containing FPBS, either 0.5, 1.0 or 2.0%, for 21 days from 7 to 28 days of age. Water and feed were given ad libitum. Feed conversion efficiency was significantly improved in chicks supplemented with 0.5 or 1.0% of FPBS as compared with the control (p<0.05). The activities of hepatic acetyl-CoA carboxylase and fatty acid synthetase, and contents of triglyceride and cholesterol in the liver were significantly decreased in treatment groups (p<0.05) as compared with the control group. FPBS had no effect on the concentration of plasma triglyceride, phospholipids and cholesterol. Feeding FPBS at 1 % or 2% levels reduced ammonia gas release (p<0.05). The inclusion of FPBS at 1 % level may be recommended both to improve production efficiency and to reduce air pollution caused by ammonia gas release. For production efficiency to reach maximal profit, the inclusion of FPBS at 0.5% level can be recommended. Feeding FPBS reduced fat accumulation in the liver.