Nonalcoholic fatty liver disease(NAFLD)is a global epidemic,affecting more than half of the people living with type 2 diabetes(T2D).The relationship between NAFLD and T2D is bidirectional and the presence of one perpe...Nonalcoholic fatty liver disease(NAFLD)is a global epidemic,affecting more than half of the people living with type 2 diabetes(T2D).The relationship between NAFLD and T2D is bidirectional and the presence of one perpetuates the other,which significantly increases the hepatic as well as extrahepatic complications.Until recently,there was no approved pharmacological treatment for NAFLD/nonalcoholic steatohepatitits(NASH).However,there is evidence that drugs used for diabetes may have beneficial effects on NAFLD.Insulin sensitizers acting through peroxisome proliferator-activated receptor(PPAR)modulation act on multiple levels of NAFLD pathogenesis.Pioglitazone(PPARγ agonist)and saroglitazar(PPARα/γagonist)are particularly beneficial and recommended by several authoritative bodies for treating NAFLD in T2D,although data on biopsyproven NASH are lacking with the latter.Initial data on elafibanor(PPARα/δ agonist)and Lanifibranor(pan PPAR agonist)are promising.On the other hand,incretin therapies based on glucagon-like peptide-1(GLP-1)receptor agonists(GLP-1RA)and dual-and triple-hormone receptor co-agonists reported impressive weight loss and may have anti-inflammatory and antifibrotic properties.GLP-1 RAs have shown beneficial effects on NAFLD/NASH and more studies on potential direct effects on liver function by dual-and triple-agonists are required.Furthermore,the long-term safety of these therapies in NAFLD needs to be established.Collaborative efforts among healthcare providers such as primary care doctors,hepatologists,and endocrinologists are warranted for selecting patients for the best possible management of NAFLD in T2D.展开更多
A new series of compounds, 2-（benzodioxol-2-yl）acetic acids, have been synthesized. Their structures were confirmed by MS and 1H-NMR. The preliminary pharmacological screening showed that these compounds exhibited p...A new series of compounds, 2-（benzodioxol-2-yl）acetic acids, have been synthesized. Their structures were confirmed by MS and 1H-NMR. The preliminary pharmacological screening showed that these compounds exhibited potent human PPARδ agonist activities.展开更多
Aim Activation of peroxisome proliferator-activated receptor δ (PPARδ) subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-...Aim Activation of peroxisome proliferator-activated receptor δ (PPARδ) subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-2 diabetes. We aim to explore the effects of peroxisome proliferator-activated receptor δ (PPARδ) subtypes on serum lipid profiles in obese rhesus monkey, especially evaluate the efficacy of investigational new drug (HS00098). Methods: First, a prototype of obese rhesus monkey was established by continuously feeding test animals a high fat diet for 2 months. Fifteen obese rhesus monkeys were randomly divided into 3 groups, and the 2 test groups were treated with GW 501516 and HS00098. The test groups were administered doses of 0.3 mg/kg for 1 month, then with 1 mg/kg for 1 month, and finally with 3 mg/kg for 1 month. The control group received placebo treatment. In each experiment, the body weight of each animal was measured and recorded initially and prior to changing the dose of the drug each month. The total cholesterol, blood glucose, triglyceride, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum Apo-A1, Apo-B100 and insulin were tested. Results: The average body weight gain of the GW501516 and HS00098 groups was significantly lower than that of the control group. The group receiving the HS00098 treatment had a higher signifycant increase in high density lipoprotein and apo-A1 (P < 0.05) than the control monkeys, while the total cholesterol, triglycerides, low density lipoproteins, apo-B100, and insulin (P < 0.05 or P < 0.01) were significantly decreased. Compared with GW50-1516, the effects of HS00098 on serum lipid profiles in diet-induced obese rhesus monkeys are more obvious. Conclusion: These results suggested that the investigational drug (HS00098) can effectively reduce body weight, blood lipid and blood sugar levels of diet-induced obese rhesus monkeys.展开更多
文摘Nonalcoholic fatty liver disease(NAFLD)is a global epidemic,affecting more than half of the people living with type 2 diabetes(T2D).The relationship between NAFLD and T2D is bidirectional and the presence of one perpetuates the other,which significantly increases the hepatic as well as extrahepatic complications.Until recently,there was no approved pharmacological treatment for NAFLD/nonalcoholic steatohepatitits(NASH).However,there is evidence that drugs used for diabetes may have beneficial effects on NAFLD.Insulin sensitizers acting through peroxisome proliferator-activated receptor(PPAR)modulation act on multiple levels of NAFLD pathogenesis.Pioglitazone(PPARγ agonist)and saroglitazar(PPARα/γagonist)are particularly beneficial and recommended by several authoritative bodies for treating NAFLD in T2D,although data on biopsyproven NASH are lacking with the latter.Initial data on elafibanor(PPARα/δ agonist)and Lanifibranor(pan PPAR agonist)are promising.On the other hand,incretin therapies based on glucagon-like peptide-1(GLP-1)receptor agonists(GLP-1RA)and dual-and triple-hormone receptor co-agonists reported impressive weight loss and may have anti-inflammatory and antifibrotic properties.GLP-1 RAs have shown beneficial effects on NAFLD/NASH and more studies on potential direct effects on liver function by dual-and triple-agonists are required.Furthermore,the long-term safety of these therapies in NAFLD needs to be established.Collaborative efforts among healthcare providers such as primary care doctors,hepatologists,and endocrinologists are warranted for selecting patients for the best possible management of NAFLD in T2D.
基金supported by the National High Technology Research and Development Program of China(863 project:2003AA235010)the National Natural Science Foundation of China(No.30472092).
文摘A new series of compounds, 2-（benzodioxol-2-yl）acetic acids, have been synthesized. Their structures were confirmed by MS and 1H-NMR. The preliminary pharmacological screening showed that these compounds exhibited potent human PPARδ agonist activities.
文摘Aim Activation of peroxisome proliferator-activated receptor δ (PPARδ) subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-2 diabetes. We aim to explore the effects of peroxisome proliferator-activated receptor δ (PPARδ) subtypes on serum lipid profiles in obese rhesus monkey, especially evaluate the efficacy of investigational new drug (HS00098). Methods: First, a prototype of obese rhesus monkey was established by continuously feeding test animals a high fat diet for 2 months. Fifteen obese rhesus monkeys were randomly divided into 3 groups, and the 2 test groups were treated with GW 501516 and HS00098. The test groups were administered doses of 0.3 mg/kg for 1 month, then with 1 mg/kg for 1 month, and finally with 3 mg/kg for 1 month. The control group received placebo treatment. In each experiment, the body weight of each animal was measured and recorded initially and prior to changing the dose of the drug each month. The total cholesterol, blood glucose, triglyceride, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum Apo-A1, Apo-B100 and insulin were tested. Results: The average body weight gain of the GW501516 and HS00098 groups was significantly lower than that of the control group. The group receiving the HS00098 treatment had a higher signifycant increase in high density lipoprotein and apo-A1 (P < 0.05) than the control monkeys, while the total cholesterol, triglycerides, low density lipoproteins, apo-B100, and insulin (P < 0.05 or P < 0.01) were significantly decreased. Compared with GW50-1516, the effects of HS00098 on serum lipid profiles in diet-induced obese rhesus monkeys are more obvious. Conclusion: These results suggested that the investigational drug (HS00098) can effectively reduce body weight, blood lipid and blood sugar levels of diet-induced obese rhesus monkeys.
