With the improvement of living standards and changes in working style, the prevalence of abnormal glucose and lipid metabolism in humans is increasing in modern society. Clinically, the related indicators are often improved by changing the lifestyle and/or taking hypoglycemic and lipid-lowering drugs, but there are no therapeutic drugs for disorders of glucose and lipid metabolism at present. Hepatitis C virus core protein binding protein 6(HCBP6) is a newly discovered target that can regulate triglyceride and cholesterol content according to level oscillations in the body, thereby regulating abnormal glucose and lipid metabolism. Relevant studies have shown that ginsenoside Rh_2 can significantly up-regulate the expression of HCBP6, but there are few studies on the effect of Chinese herbal medicines on HCBP6. Moreover, the three-dimensional structural information of HCBP6 has not been determined and the discovery of potential active components acting on HCBP6 is not rapidly advanced. Therefore, the total saponins of eight Chinese herbal medicines commonly used to regulate abnormal glucose and lipid metabolism were selected as the research objects to observe their effect on the expression of HCBP6. Then, the three-dimensional structure of HCBP6 was predicted, followed by molecular docking with saponins in eight Chinese herbal medicines to quickly find potential active components. The results showed that all total saponins tended to up-regulate HCBP6 mRNA and protein expression, where gypenosides showed the optimum effect on up-regulating HCBP6 mRNA and ginsenosides showed the optimum effect on up-regulating HCBP6 protein expression. Reliable protein structures were obtained after the prediction of protein structures using the Robetta website and the evaluation of the predicted structures by SAVES. The saponins from the website and literature were also collected and docked with the predicted protein, and the saponin components were found to have good binding activity to the HCBP6 protein. The results of the study are expected to provide ideas and methods for the discovery of new drugs from Chinese herbal medicines to regulate glucose and lipid metabolism.
Humans ; Glucose ; Lipid Metabolism ; Molecular Docking Simulation ; Drugs, Chinese Herbal/pharmacology* ; Ginsenosides ; Proteins ; Saponins ; RNA, Messenger

Lipid Droplets/metabolism* ; Bacteria ; Lipid Metabolism

Objective To investigate the effects of long noncoding RNA H19 on lipid accumulation of macrophages under high fat stress and its mechanism. Methods Human THP-1 cells-derived macrophages were incubated with ox-LDL, and the effects of H19 siRNA intervention on lipid accumulation was observed. The THP-1 cells were divided into control group (conventional culture), ox-LDL group, siRNA negative control (NC siRNA) combined with ox-LDL treatment group, and H19 siRNA combined with ox-LDL treatment group. Oil red O staining was used to determine the lipid accumulation in cells, and cholesterol concentration was analyzed by enzymatic method; ATP assay kit for detecting celluar ATP content; colorimetry was used to detect the levels of oxidative stress indicators and ELISA was used to detect the levels of monocyte chemoattractant protein-1 (MCP-1) in the cell supernatant. Western blot analysis was used to detect the protein expression of ATP binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and nuclear factor κB p-p65 (NF-κB p-p65). Results Knockdown H19 significantly inhibited intracellular lipid accumulation, decreased total cholesterol (TC) and cholesterol ester (CE) content, and decreased CE/TC ratio. Knockdown H19 significantly alleviated cell damage including an increase in ATP content, a decrease in oxidative stress levels and a decrease in MCP-1 levels, which caused by high-fat stress. H19 siRNA upregulated expression of ABCA1, PPARα and PGC-1α in THP-1 derived macrophages, downregulated NF-κB signal pathway. Conclusion Knockdown H19 upregulates PGC-1α expression in THP-1 cells and downregulates NF-κB pathway, which promotes cholesterol reverse transport, reduces inflammatory reaction and inhibits lipid accumulation.
Humans ; Adenosine Triphosphate ; Cholesterol ; NF-kappa B ; PPAR alpha ; RNA, Long Noncoding/genetics* ; RNA, Small Interfering/genetics* ; THP-1 Cells ; Macrophages/metabolism* ; Lipid Metabolism

OBJECTIVES: To explore the mechanism of Chinese medicine Jiangzhuo mixture regulating glucose and lipid metabolism in obese rats. METHODS: Thirty healthy male SD rats were randomly divided into normal control group, model control group, and Jiangzhuo mixture treatment group, with 10 rats in each group. The rats in the normal control group were fed with normal diet, the obesity model was induced by feeding high-fat diet in the model control group and the Jiangzhuo mixture treatment group, the rats in the treatment group were given with Jiangzhuo mixture 50 g/kg by gavage. After 8 weeks of intervention, the blood glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured in the three groups. Quantitative reverse transcription PCR were used to detect the expression levels of PR domain containing 16 (PRDM16) and uncoupling protein 1 (UCP1) in white and brown adipose tissues of the rats in each group; Western blotting was used to detect the expression of PRDM16 in the white and brown adipose tissue of rats, and Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) and inhibitor of NF-κB alpha (IκBα) in the white adipose tissue; immunohistochemistry was used to detect the expression of UCP1 protein in white and brown adipose tissues. RESULTS: Compared with the normal control group, the white fat weight (P<0.01), white fat coefficient (P<0.05) and Lee's coefficient (P<0.01) were significantly increased in the model control group; the contents of GLU, TC, TG and LDL-C were all increased, and the content of TG was significantly increased (P<0.05) in the model control group. The mRNA and protein expression levels of PRDM16 and UCP1 in white fat and brown fat were significantly decreased (P<0.05) in the model control group. Compared with the model control group, the white fat weight and white fat coefficient and Lee's coefficient were significantly reduced in the Jiangzhuo mixture treatment group (all P<0.01), the levels of GLU, TC, TG, and LDL-C in the the treatment group were all reduced, and the content of TG was reduced more obviously (P<0.01); expression levels of PRDM16 and UCP1 mRNA and protein were increased in brown and white adipose tissue. Compared with the normal control group, the expression levels of TLR4, phospho-IκBα and NF-κB-p65 proteins in white adipose tissue of the model control group were significantly increased (all P<0.01), while the expression levels of these proteins in the treatment group were significantly lower than those in the model control group (all P<0.05). CONCLUSIONS Jiangzhuo mixture can alleviate high-fat diet-induced increase in body fat, abnormal expression of biochemical indexes and promote the expression of key proteins including UCP1 and PRDM16 in white and brown adipose tissues by regulating TLR4/IκBα/NF-κB signaling pathway.
Rats ; Male ; Animals ; NF-kappa B/metabolism* ; Rats, Sprague-Dawley ; Glucose ; Lipid Metabolism ; Toll-Like Receptor 4 ; Cholesterol, LDL/metabolism* ; NF-KappaB Inhibitor alpha/metabolism* ; Medicine, Chinese Traditional ; Signal Transduction ; Triglycerides ; Transcription Factors/metabolism* ; Obesity ; RNA, Messenger

Carrier Proteins ; Autophagy ; Lipid Metabolism

Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, ORP8 has increased localization on LDs and is phosphorylated by AMPK, thereby enhancing its affinity for LC3/GABARAPs. Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride. Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice, and Osbpl8-/- mice exhibit liver lipid clearance defects. Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.
Animals ; Mice ; Lipid Droplets ; Autophagy ; Autophagosomes ; Homeostasis ; Triglycerides

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

OBJECTIVES: To observe the effects on the glucose-lipid metabolism and the expression of zinc-α2-glycoprotein (ZAG) and glucose transporter 4 (GLUT4) in the femoral quadriceps and adipose tissue after electroacupuncture (EA) at "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) in the rats with diabetes mellitus type 2 (T2DM), so as to explore the effect mechanism of EA in treatment of T2DM. METHODS: Twelve ZDF male rats were fed with high-sugar and high-fat fodder, Purina #5008 for 4 weeks to induce T2DM model. After successfully modeled, the rats were randomly divided into a model group and an EA group, with 6 rats in each one. Additionally, 6 ZL male rats of the same months age were collected as the blank group. The rats in the EA group were treated with EA at bilateral "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), with continuous wave, 15 Hz in frequency, and 2 mA in intensity. The electric stimulation lasted 20 min each time. EA was delivered once daily, 6 times a week for 4 weeks. Separately, the levels of fasting blood glucose (FBG) was measured before modeling, before and after intervention, and the body mass of each rat was weighted before and after intervention. After intervention, the levels of the total cholesterol (TC), triacylglycerol (TG) and free fatty acid (FFA) in serum were detected using enzyme colorimetric method; and the levels of the serum insulin (INS) and ZAG were detected by ELISA. Besides, the insulin sensitivity index (HOMA-ISI) was calculated. With Western blot technique adopted, the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue were determined. RESULTS: After intervention, compared with the blank group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS increased (P<0.01), while HOMA-ISI decreased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue dropped (P<0.01) in the model group. In the EA group, compared with the model group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS were reduced (P<0.01), and HOMA-ISI increased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue increased (P<0.01, P<0.05). CONCLUSIONS Electroacupuncture can effectively regulate glucose-lipid metabolism, improve insulin resistance and sensitivity in the rats with T2DM, which is associated with the modulation of ZAG and GLUT4 expression in the skeletal muscle and adipose tissue.
Rats ; Male ; Animals ; Glucose/metabolism* ; Electroacupuncture ; Rats, Sprague-Dawley ; Diabetes Mellitus, Type 2/therapy* ; Lipid Metabolism ; Triglycerides ; Adipose Tissue/metabolism* ; Acupuncture Points

Lipids droplets are organelles that store neutral lipids and are closely related to lipid accumulation. Long chain acyl-coenzyme A synthetase 3 (ACSL3) is a lipid droplet-associated protein mainly distributed in the cell membrane, endoplasmic reticulum, and intracellular lipid droplets, and its distribution depends on cell type and fatty acid supply. ACSL3 is a key regulator of fatty acid metabolism that is closely related to intracellular lipid accumulation, and plays an important role in various pathophysiological processes such as lipid droplet synthesis and lipid metabolism, cellular inflammation, and ferroptosis. This paper mainly reviews the role of ACSL3 in lipid synthesis, ferroptosis, and inflammatory response, with focus on the mechanism of its role in lipid accumulation in atherosclerosis, and provides new ideas for exploring potential therapeutic targets in atherosclerotic diseases.
Humans ; Atherosclerosis ; Coenzyme A Ligases/metabolism* ; Endoplasmic Reticulum/metabolism* ; Fatty Acids/metabolism* ; Lipid Metabolism

As a member of the apolipoprotein C (ApoC) family with a relatively high content, ApoC3 plays a major role in the regulation of triglyceride metabolism, and plays an important role in the occurrence and development of cardiovascular diseases, glucose and lipid metabolism disorders. Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of a large amount of fat in the liver in the absence of a history of chronic alcohol consumption or other damage to the liver. A large number of previous studies have shown that there is a correlation between the gene polymorphism and high expression of ApoC3 and NAFLD. In the context of hypertriglyceridemia (HTG), this article reviews the relationship between ApoC3 and NAFLD, glucose and lipid metabolism, and islet β cell function, showing that ApoC3 can not only inhibit lipoprotein lipase (LPL) and hepatic lipase (HL) activity, delay the decomposition of triglyceride in plasma to maintain the body's energy metabolism during fasting, but also be significantly increased under insulin resistance, prompting the liver to secrete a large amount of very low-density lipoprotein (VLDL) to induce HTG. Therefore, targeting and inhibiting ApoC3 might become a new approach to treat HTG. Increasing evidence suggests that ApoC3 does not appear to be an independent "contributor" to NAFLD. Similarly, our previous studies have shown that ApoC3 is not an independent factor triggering islet β cell dysfunction in ApoC3 transgenic mice, but in a state of excess nutrition, HTG triggered by ApoC3 high expression may exacerbate the effects of hyperglycemia and insulin resistance on islet β cell function, and the underlying mechanism remains to be further discussed.
Apolipoprotein C-III/genetics* ; Non-alcoholic Fatty Liver Disease/pathology* ; Glucose/metabolism* ; Lipid Metabolism ; Humans ; Animals ; Hypertriglyceridemia/metabolism* ; Islets of Langerhans/metabolism*