• Nutrition Research and Practice
• /
• 제18권4호
• /
• pp.479-497
• /
• 2024

BACKGROUND/OBJECTIVES: Activating brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can protect against obesity and obesity-related metabolic conditions. Cryptotanshinone (CT) regulates lipid metabolism and significantly ameliorates insulin resistance. Adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), a receptor for cellular energy metabolism, is believed to regulate brown fat activity in humans. MATERIALS/METHODS: The in vivo study included high-fat-fed obese mice administered orally 200/400 mg/kg/d CT. They were evaluated through weight measurement, the intraperitoneal glucose tolerance test (IPGTT), intraperitoneal insulin tolerance test (IPITT), cold stimulation test, serum lipid (total cholesterol, triglycerides, and low-density lipoprotein) measurement, hematoxylin and eosin staining, and immunohistochemistry. Furthermore, the in vitro study investigated primary adipose mesenchymal stem cells (MSCs) with incubation of CT and AMPK agonists (acadesine)/inhibitor (Compound C). Cells were evaluated using Oil Red O staining, Alizarin red staining, flow cytometry, and immunofluorescence staining to identify and observe the osteogenic versus adipogenic differentiation. Quantitative real-time polymerase chain reaction and the Western blot were used to observe related gene expression. RESULTS: In the diet-induced obesity mouse model mice CT suppressed body weight, food intake, glucose levels in the IPGTT and IPTT, serum lipids, the volume of adipose tissue, and increased thermogenesis, uncoupling protein 1, and the AMPK pathway expression. In the in vitro study, CT prevented the formation of lipid droplets from MSCs while activating brown genes and the AMPK pathway. AMPK activator enhanced CT's effects, while the AMPK inhibitor reversed the effects of CT. CONCLUSION: CT promotes adipose tissue browning to increase body thermogenesis and reduce obesity by activating the AMPK pathway. This study provides an experimental foundation for the use of CT in obesity treatment.

• 대한한의학방제학회지
• /
• 제22권1호
• /
• pp.167-176
• /
• 2014

Objectives : This study investigated the improvement effects of Gangjihwan (DF) and combination of Gangjihwan and Gamisochehwan (GSH) on nonalcoholic fatty liver disease in a high fat diet-induced obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into five groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and atorvastatin, DF, and DF+GSH groups given a high fat diet with atorvastatin (10 mg/kg), DF (40 mg/kg), and DF+GSH (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, blood lipid markers, ALT concentrations, liver weight and histology were examined. Results : 1. Body weight gain was significantly decreased in DF, DF+GSH and atorvastatin groups compared with control. The extent of decreases was eminent in DF+GSH group. 2. Circulating concentrations of total cholesterol, HDL-cholesterol and LDL-cholesterol were decreased in DF, DF+GSH and atorvastatin groups compared with control. The decreases were significant in DF+GSH and atorvastatin groups. 3. Liver weights were decreased in DF, DF+GSH and atorvastatin groups compared with control. In particular, liver weight was significantly reduced only in DF+GSH group. 4. Hepatic lipid accumulation was significantly decreased in DF, DF+GSH and atorvastatin groups compared with control, and the magnitude of which was more effective in DF+GSH group than in DF-only group. 5. Circulating ALT concentrations were decreased in DF, DF+GSH and atorvastatin compared with control, but ALS levels were significantly reduced only in DF+GSH group. Conclusions : In conclusion, these results suggest that DF decreases body weight gain, improves blood lipid metabolism, and reduces liver weight and hepatic lipid accumulation, contributing to the improvement of nonalcoholic fatty liver disease. In addition, these effects were more effective in DF+GSH combination group than in DF-only group.

• 대한한의학방제학회지
• /
• 제22권1호
• /
• pp.113-122
• /
• 2014

Objectives : This study investigated the improvement effects of Pakistani (DF-a) and Chinese Ephedra herba-containing Gangjihwan (DF-b) on nonalcoholic fatty liver disease in a high fat diet-induced obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into five groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and atorvastatin, DF-a, and DF-b groups given a high fat diet with atorvastatin (10 mg/kg), DF-a (80 mg/kg), and DF-b (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, blood lipid markers, ALT concentrations, liver weight and histology were examined. Results : 1. Body weight gain was significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control. The extent of decreases was eminent in DF-a group. 2. Circulating concentrations of total cholesterol and LDL-cholesterol were significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control. The decreases were most effective in atorvastatin group. 3. Liver weights were decreased in DF-a, DF-b, and atorvastatin groups compared with control. In particular, liver weight was significantly reduced in DF-b group. 4. Hepatic lipid accumulation was significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control, and the magnitude of which was most effective in DF-b group. 5. Circulating ALT concentrations were decreased in DF-a, DF-b, and atorvastatin groups compared with control, but ALS levels were significantly reduced only in DF-b group. Conclusions : In conclusion, these results suggest that DF-a and DF-b decrease body weight gain, improve blood lipid metabolism, and reduce liver weight and hepatic lipid accumulation, contributing to the improvement of nonalcoholic fatty liver disease. In addition, these effects were similar between Pakistani and Chinese Ephedra herba-containing Gangjihwan.

• 생명과학회지
• /
• 제32권7호
• /
• pp.532-541
• /
• 2022

고지방식이(High fat diet, HFD)에 의해 유발되는 비만은 정상적인 마우스에서는 연구되지 않았지만 여러 유전자변형마우스의 전립선암(Prostate cancer)에 대한 강력한 위험인자 및 예후인자로 검증되었다. HFD-유도 비만이 정상적인 마우스에서 전립선암의 발생 및 진행에 영향을 미칠 수 있는지 여부를 조사하기 위해, 16주 동안 60% HFD 식이를 급여한 비만 C57BL/6N 마우스에서 전립선의 무게 및 조직학적 구조 변화와 암관련 단백질 발현을 분석하였다. 첫째, HFD 식이를 급여한 C57BL/6N 마우스는 체중, 장기의 무게, 지방축적, 혈청지질 수치의 증가 등을 포함한 비만증상을 성공적으로 유도되었다. 전립선의 무게는 No그룹에 비해 HFD-유도 비만마우스에서 유의미하게 증가하였다. 전립선의 4가지 엽들 중 외측전립선(Dorsolateral prostate, DLP)과 정낭(Seminal vesicle, SV)의 무게는 유의적인 변화가 없었지만, 복부전립선(Ventral prostate, VP)과 전방전립선(Anterior prostate, AP)의 무게는 No그룹보다 HFD-유도 비만마우스에서 증가하였다. 또한, 전립선의 조직학적 구조에서 과형성(Hyperplasia) 및 비호지킨림프종(Non-hodgkin's lymphoma, NHL)의 발생률은 HFD-유도 비만마우스에서 유의미하게 증가하였으며, 같은 그룹에서 AP의 상피두께도 증가하였다. HFD-유도 비만마우스에서 AKT (Protein kinase B) 신호경로에서 주요 단백질의 인산화수준이 유의미하게 증가했다. 따라서 이러한 결과는 HFD-유도 비만은 C57BL/6N 마우스에서 전립선암의 발생과 진행을 촉진할 수 있음을 시사한다.

• 생명과학회지
• /
• 제20권7호
• /
• pp.1012-1018
• /
• 2010

본 연구에서, 고지방식이에 의한 비만, streptozotocin처리에 의한 당뇨 및 노화에 의해 알츠하이머병의 원인 유전자인 APP의 발현이상이 생기는지를 조사하였다. 일반식이(ND)/고지방식이(HFD), 16주령/26주령, 및 정상/당뇨 등의 조건별 8가지 조합에 88마리의 C57BL/6 생쥐를 각 그룹에 최소 10마리씩 나누어 키웠으며, 각 실험생쥐로부터 추출한 부고피하지방 및 부고환지방조직에서의 APP mRNA 발현양을 quantitative real-time PCR로 측정하였다. 그 결과, 피하지방조직에서의 APP 유전자는 16주령과 26주령에서 고지방식이로 키워 비만을 유도한 동물에서 2배정도 높게 발현되었으나(16주령 $125.0{\pm}13.9$ vs. $63.5{\pm}9.9$, p=0.001; 26주령 $120.2{\pm}6.0$ vs. $51.8{\pm}6.3$, p<0.0001), 부고환지방조직에서는 APP 발현양의 차이가 나타나지 않았다. 16주령과 26주령 사이에서의 노화에 따른 APP 발현양의 차이도 나타나지 않았다. 또한, 일반 및 고지방식이로 키운 16주령 생쥐의 피하지방조직 APP 유전자 발현은 STZ에 의해 유도된 당뇨병 생쥐에서 크게 감소되었다(ND non-diabetic $63.5{\pm}9.9$ vs. diabetic $40.2{\pm}5.0$, p<0.05; HFD $125.0{\pm}13.9$ vs. $67.0{\pm}9.0$, p<0.01). APP mRNA 발현양의 선형회귀분석에 의하면, 당뇨병이 유발되지 않은 일반 생쥐(R=0.657, p<0.0001, n=39)와 당뇨병 생쥐(R=0.508, p=<0.0001, n=49) 모두에서의 APP mRNA 발현양이 체중과 깊은 연관성이 있음이 확인되었으나, APP mRNA 양과 혈당과의 연관성은 나타나지 않았다. 이는 STZ에 의한 당뇨병 생쥐에서 관찰된 APP mRNA 발현의 감소는 고혈당증에 의한 것이 아닌 체중감소의 영향인 것으로 추측된다. 본 연구의 결과로 APP mRNA는 생쥐의 피하지방 및 부고환지방에서 발현되고 있고, 비만에의 의해 증가하며, 체중감소에 의해 감소한다는 것을 확인하였다. 이들 결과는 사람에게서 확인된 체중변화에 의한 APP 이상발현 현상을 더욱 분명히 보여주었으며, 이런 APP 이상발현이 중년기 비만과 노령기의 알츠하이머병 환자 뇌에서의 amyloidogenesis 증가 매개자로서의 역할 가능성을 시사한다.