• Molecules and Cells
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• v.43 no.8
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• pp.686-693
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• 2020

Autophagy is an intracellular degradation system that breaks down damaged organelles or damaged proteins using intracellular lysosomes. Recent studies have also revealed that various forms of selective autophagy play specific physiological roles under different cellular conditions. Lipid droplets, which are mainly found in adipocytes and hepatocytes, are dynamic organelles that store triglycerides and are critical to health. Lipophagy is a type of selective autophagy that targets lipid droplets and is an essential mechanism for maintaining homeostasis of lipid droplets. However, while processes that regulate lipid droplets such as lipolysis and lipogenesis are relatively well known, the major factors that control lipophagy remain largely unknown. This review introduces the underlying mechanism by which lipophagy is induced and regulated, and the current findings on the major roles of lipophagy in physiological and pathological status. These studies will provide basic insights into the function of lipophagy and may be useful for the development of new therapies for lipophagy dysfunction-related diseases.

• International Journal of Oral Biology
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• v.43 no.1
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• pp.23-27
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• 2018

Increased intracellular levels of $Ca^{2+}$ are generally thought to negatively regulate lipolysis in mature adipocytes, whereas store-operated $Ca^{2+}$ entry was recently reported to facilitate lipolysis and attenuate lipotoxicity by inducing lipophagy. Transient receptor potential mucolipin1 (TRPML1), a $Ca^{2+}$-permeable non-selective cation channel, is mainly expressed on the lysosomal membrane and plays key roles in lysosomal homeostasis and membrane trafficking. However, the roles of TRPML1 in lipolysis remains unclear. In this study, we examined whether the channel function of TRPML1 induces lipolysis in mature adipocytes. We found that treatment of mature adipocytes with ML-SA1, a specific agonist of TRPML1, solely upregulated extracellular glycerol release, but not to the same extent as isoproterenol. In addition, knockdown of TRPML1 in mature adipocytes significantly reduced autophagic flux, regardless of ML-SA1 treatment. Our findings demonstrate that the channel function of TRPML1 partially contributes to lipid metabolism and autophagic membrane trafficking, suggesting that TRPML1, particularly the channel function of TRPML1, is as therapeutic target molecule for treating obesity.

• Molecules and Cells
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• v.45 no.9
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• pp.649-659
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• 2022

A long-term energy nutritional imbalance fundamentally causes the development of obesity and associated fat accumulation. Lysosomes, as nutrient-sensing and lipophagy centers, critically control cellular lipid catabolism in response to nutrient deprivation. However, whether lysosome activity is directly involved in nutrient-induced fat accumulation remains unclear. In this study, worm fat accumulation was induced by 1 mM glucose or 0.02 mM palmitic acid supplementation. Along with the elevation of fat accumulation, lysosomal number and acidification were also increased, suggesting that lysosome activity might be correlated with nutrient-induced fat deposition in Caenorhabditis elegans. Furthermore, treatments with the lysosomal inhibitors chloroquine and leupeptin significantly reduced basal and nutrient-induced fat accumulation in C. elegans. The knockdown of hlh-30, which is a critical gene in lysosomal biogenesis, also resulted in worm fat loss. Finally, the mutation of aak-2, daf-15, and rsks-1 showed that mTORC1 (mechanistic target of rapamycin complex-1) signaling mediated the effects of lysosomes on basal and nutrient-induced fat accumulation in C. elegans. Overall, this study reveals the previously undescribed role of lysosomes in overnutrition sensing, suggesting a new strategy for controlling body fat accumulation.

• The Journal of Internal Korean Medicine
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• v.19 no.2
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• pp.392-410
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• 1998

In order to investigate the effect of Alismatis Lhizoma on hyperlipidemia, experimental studies were performed on hyperlipidemia rats. Hyperlipidemia model (controll group) was induced by 1% cholesterol fed-diet for 8 weeks. Sample I group fed with 1% cholesterol and 4% Alismatis Lhizoma diet for 8 weeks. Sample II group fed with 1% cholesterol and 8% Alismatis Lhizoma diet for 8 weeks. The contents of serum total cholesterol, triglyceride, free fatty acid, phospholipid, HDL-cholesterol and LDL-cholesterol were measured, and fat accumulation in liver and the change of elastic and collagenous fiber in aortic wall were observed. The results were summurized as follows ; 1. The content of total cholesterol in the serum compared with control group tended to be decreased in sample group, and then sample I group showed a significant value. 2. The content of triglyceride in the serum compared with control group tended to be decreased in sample group, and then sample I group showed a significant value. 3. The content of free fat acid in the serum compared with control group tended to be decreased in sample group, but did not show a significance. 4. The content of phospholipid in the serum compared with control group tended to be decreased in sample group, and then sample I group showed a significant value. 5. The content of HDL-cholesterol in the serum compared with control group tended to be increased in sample group, and then sample II group showed a significant value. 6. The content of LDL-cholesterol in the serum compared with control group tended to be decreased in sample group, and then sample I group showed a significant value. 7. The lipophagy in liver compared with control group tended to be repressed in sample group. 8. The change of elastic and collagenous fiber lesion in tunica media of aortic wall, compared with control group tended to be repressed in sample group. According to the above results, it is assumed that Alismatis Lhizoma has a valid effect on hyperlipidemia. And yet, it needs to make further researches that sample I group showed more significant value than sample II group.

• The Journal of Internal Korean Medicine
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• v.19 no.2
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• pp.347-366
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• 1998

In order to investigate the effect of Lycii Radicis Cortex on hyperlipidemia, experimental studies were performed on hyperlipidemia rats. Hyperlipidemia model (controll group) was induced by 1% cholesterol fed-diet for 8 weeks. Sample I group fed with 1% cholesterol and 4% Lycii Radicis Cortex diet for 8 weeks. Sample II group fed with 1% cholesterol and 8% Lycii Radicis Cortex diet for 8 weeks. The contents of serum total cholesterol, triglyceride, free fatty acid, phospholipid, HDL-cholesterol and LDL-cholesterol were measured, and fat accumulation in liver and the change of elastic and collagenous fiber in aortic wall were observed. The results were summurized as follows ; 1. The content of total cholesterol in the serum compared with control group tended to be decreased in sample group, but did not show a significance. 2. The content of triglyceride in the serum compared with control group tended to be decreased in sample group, and then sample II group showed a significant value. 3. The content of free fat acid in the serum compared with control group tended to be decreased in sample group, and then sample II group showed a significant value. 4. The content of phospholipid in the serum compared with control group tended to be decreased in sample group, but did not show a significance. 5. The content of HDL-cholesterol in the serum compared with control group tended to be increased in sample group, and then sample I group showed a significant value. 6. The content of LDL-cholesterol in the serum compared with control group tended to be decreased in sample group, and then sample I group showed a significant value. 7. The lipophagy in liver compared with control group tended to be decreased in sample group. 8. The change of elastic and collagenous fiber lesion in tunica media of aortic wall, compared with control group tended to be decreased in sample group. According to the above results, it is assumed that Lycii Radicis Cortex has a valid effect on hyperlipidemia. Therefore, it seems to be applicable to the diseases related to hyperlipidemia.

• The Journal of Internal Korean Medicine
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• v.29 no.3
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• pp.703-715
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• 2008

This experiments was performed to determine the effects of Gangzitongmaekeum(降脂通脈飮 : GTE) on antioxidation activity and hyperlipidemia induced by hypercholesterolemic diet in mice. The results obtained were as follows : 1. GTE showed a safety in cytotoxicity and toxicity of human fibroblast cells and liver. 2. GTE showed DPPH scavenging activity, superoxide dismutase (SOD)-like activity and inhibitory effect on reactive oxygen species (ROS). 3. GTE treated mice showed body and liver weight decrease, compared to the hyperlipidemia-induced control group. 4. GTE decreased total cholesterol and LDL cholesterol levels significantly, but HDL cholesterol levels not significantly. 5. GTE decreased triglyceride levels significantly. 6. Glucose levels in GTE treated mice significantly decreased compared to the hyperlipidemia-induced control group. 7. Albumin levels in GTE treated mice were similar with the hyperlipidemia-induced control group. 8. The lipophagy in liver compared with the control group tended to be decreased in GTE treated mice. In the change of aorta, the cell was regular and boundary of vessel wall was clear, compared to the hyperlipidemia-induced control group. 9. TBARS levels in GTE treated mice significantly decreased compared to the hyperlipidemia-induced control group. 10. The change of SOD and catalase activity significantly increased compared to the hyperlipidemia-induced control group. 11. ACAT mRNA level and HMG-CoA reductase mRNA levels in GTE treated mice significantly decreased compared to the hyperlipidemia-induced control group. Conclusion : These results suggest that Gangzitongmaekeum is effective in antioxidation activity and dietary hyperlipidemia-induced mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.3
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• pp.164-176
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• 2016

This study was perfomed to investigate the effects of Chunghyul-plus(CHP) on oxidative damage and hyperlipidemia in db/db mouse. After treatment with CHP, safety in cytotoxicity, heavy metal toxicity, production of reactive oxygen species(ROS), nitric oxide (N0) and proinflammatory cytokine IL-Ib, TNF-a, IL-6 in RAW 264.7 cells. Serum total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, insulin, GLP-1, glucose, food intake, body weight, organ weight, AST, ALT, ALP, BUN, creatine and histologic change of liver and aorta were measured in db/db mouse after oral administration of CHP. CHP showed safety in cytotoxicity and toxicity of liver and kidney for logn time administration. CHP increased the DPPH and ABTS radical scavenging activity. CHP showed significant inhibitory effect on reactive oxygen species (ROS), and showed inhibitory effect on nitiric oxide(NO) compared to control group. CHP decreased cytokine IL-6 production significantly, and decreased IL-1β and TNF-α compared to control group. CHP decreased body and organ weitht, intake food, and glucose levels compared to control group. CHP decreased total cholesterol and triglyceride significantly, and decreased LDL-cholesterol levels and increased HDL-cholesterol levels compared to control group. CHP decreased atherogenic index and cardiac risk factor significantly. CHP increased serum insulin and GLP-1 compared to control group. In histologic examination, lipophagy in the liver and aorta decreased in CHP treated mice and the cell was regular and boundary of vessel wall was clear compared to control group. These results suggest that CHP is effective in antioxidation activity and treatment and prevention of hyperlipidemia, atherosclerosis, diabetes, ischemic heart disease, stroke and other cardiocerebrovascular disease.