Traditional treatment of type 2 diabetes mellitus (T2DM) has focused on correcting hyperglycemia. However, T2DM is almost always accompanied by other conditions and risk factors that affect its morbidity and mortality...Traditional treatment of type 2 diabetes mellitus (T2DM) has focused on correcting hyperglycemia. However, T2DM is almost always accompanied by other conditions and risk factors that affect its morbidity and mortality. Obesity represents one of the main risk factors associated in the T2DM and a modest weight loss around 5% is linked with significant reduction in the blood glucose levels. The objective of this study was to compare the pharmacokinetic parameters between two formulations of metformin, alone or combined with orlistat, in healthy volunteers. A single-blinded, single dose, two-period, two-sequence, crossover, randomized and balanced study design with a 7-day washout period was performed in 26 Mexican volunteers. Plasma samples were collected over a 24-hour period after administration of 500 mg metformin alone or combined with 60 mg orlistat in each period. A validated high-performance liquid chromatography coupled with a ultraviolet detector was used to analyze metformin concentration in plasma. Bioequivalence between metformin alone and metformin combined with orlistat was determined when the ratio for the 90% confidence intervals (CI) of area under the curve (AUC24h) and maximum concentration (Cmax) of the two formulations were within 80% and 125%. In the current study, the mean ± standard deviation (SD) of Cmax, AUC24h and AUC∞ of the formulation containing only metformin were 1.39 ± 0.44 μg/mL, 7.59 ± 3.17 μg h/mL and 8.48 ± 4.13 μg h/mL, respectively, while the mean ± SD of Cmax, AUC24h and AUC∞ of the formulation containing metformin and orlistat were 1.38 ± 0.48 μg/mL, 7.80 ± 2.83 μg h/mL and 9.13 ± 4.29 μg h/mL, respectively. The parametric 90% CI for Cmax and AUC24h were 87.5-109.3 and 88.7-124.7, respectively. These results suggest that both formulations are bioequivalent and there is not pharmacokinetic interaction between metformin and orlistat.展开更多
Orlistat is a safe and effective drug to treat obesity by acting as a pancreatic and gastric lipase inhibitor, resulting in reduction in fat absorption. There is also concern that it may be linked with an increased th...Orlistat is a safe and effective drug to treat obesity by acting as a pancreatic and gastric lipase inhibitor, resulting in reduction in fat absorption. There is also concern that it may be linked with an increased threat of serious hepatic incidents. The present work was carried out to study the effect of orlistat on the histological, immunohistochemical and electron microscopic structure of the liver in the adult male albino rats and the possible protective role of β-carotene administration. Forty adult albino rats were subjected to experiment for two weeks as follows: group 1 (control), group II, each animal received 0.52 mg/kg bw/day β-Carotene, group III, each animal received orlistat 32 mg/kg/day, and group IV received β-Carotene, 1hour before the administration of orlistat at same dose of group II & III. The liver from each animal was dissected out and processed for histological, (light and electron microscopic study). The result of Hep-Par1 for immunohistochemistry was statistically analyzed. The results showed that orlistat treated group displayed variable disturbance of liver architecture, from dilatation, congested central and portal veins, branching of bile ductules, mononuclear cellular infiltration, areas of hemorrhages, cytoplasmic vacuolation and pyknotic nuclei. The most obvious changes were that degenerative changes in hepatocytes led to depletion of glycogen content of hepatocytes. Hep Par-1 revealed a wide area of negative immune expression around the central vein and in some hepatocytes. Other hepatocytes expressed weak reaction. Ultrastructure examination displayed hepatocytes with swollen mitochondria and others with an electron-dense matrix. The combined treatment of β-Carotene and orlistat led to a marked improvement in most of the previously mentioned changes. It was concluded that orlistat-induced hepatic toxicity. Thus, clinicians should cautiously monitor their patients for signs of hepatic dysfunction. Using an antioxidant such as β-Carotene decreased the toxicity of orlistat.展开更多
Objectives To observe the influence of weight loss induced by orlistat on several cardiovascular diseases risk factors in obese Chinese subjects. Methods Sixty obese Chinese patients participated in a 24 week clinical...Objectives To observe the influence of weight loss induced by orlistat on several cardiovascular diseases risk factors in obese Chinese subjects. Methods Sixty obese Chinese patients participated in a 24 week clinical trial. Participants were prescribed a slightly hypocaloric diet and exercise, then they were randomly assigned double -blind treatment with either orlistat 120 mg three times a day or placebo. Their body weight, blood pressure, fasting glucose, insulin, HbA1c, and serum lipid profile were performed before and after the weight loss intervention. Results After 24 weeks, orlistat -treated group lost more of their body weight than placebo group (6. 66 ± 0. 52 kg, 8. 44±4.08% and 1. 98 ± 0. 44 kg, 2. 44±1. 74 % , respectively, P < 0. 05) . Moreover, after treatment, orlistat - treated patients showed significant decreases in serum levels of total cholesterol, low density lipoprotein - cholesterol and high density lipoprotein - cholesterol ( P < 0.01), but in placebo group we found no change. Both systolic blood pressure and diastolic blood pressure fell significantly in orlistat - treated group. Fasting glucose and HOMA - IR in orlistat - treated group was distinctly reduced if compared with placebo group. Conclusions Weight loss resulting from orlistat treatment and slightly hypocaloric diet has produced favorable effects on several cardiovascular risk factors in obese Chinese subjects.展开更多
Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers,including lung cancer;however,targeting the lipogenetic pathways for cancer therapy remains an unmet cl...Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers,including lung cancer;however,targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need.In this study,we tested the anticancer activity of orlistat,an FDA-approved anti-obesity drug,in human and mouse cancer cells in vitro and in vivo,and we found that orlistat,as a single agent,inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro.Mechanistically,we found that orlistat reduced the expression of GPX4,a central ferroptosis regulator,and induced lipid peroxidation.In addition,we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2,a molecule regulating the lipid droplet homeostasis,as a novel target of orlistat.Moreover,in a mouse xenograft model,orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control(P<0.05).Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.展开更多
Polycystic ovary syndrome(PCOS)is a common gynecological endocrine syndrome characterized by metabolic abnormality and reproductive dysfunction,including ovulation abnormality,hyperandrogenism and polycystic ovarian m...Polycystic ovary syndrome(PCOS)is a common gynecological endocrine syndrome characterized by metabolic abnormality and reproductive dysfunction,including ovulation abnormality,hyperandrogenism and polycystic ovarian manifestations.Most PCOS patients are overweight or obese,particularly the central type.This aggravates the clinical manifestations of PCOS and ultimately increases the risk of infertility.Orlistat is the only weight loss drug approved by the US Food and Drug Administration.As a long-lasting gastrointestinal lipase inhibitor,orlistat can effectively reduce the absorption of lipid and increase lipid excretion,thereby achieving weight loss.In obese PCOS patients,orlistat can reduce weight,improve lipid metabolism and insulin resistance,improve sex hormone disorder,and have a positive effect on pregnancy outcome.This review summarizes the impact of orlistat treatment on metabolism and fertility in obese women with PCOS.展开更多
（-）-Tetrahydrolipstatin 1 was synthesized in three steps and 33.8% overall yield from aldehyde 6 by tandem Mukaiyama-aldol lactonization, which offered a concise, efficient and highly diastereoselective route to thi...（-）-Tetrahydrolipstatin 1 was synthesized in three steps and 33.8% overall yield from aldehyde 6 by tandem Mukaiyama-aldol lactonization, which offered a concise, efficient and highly diastereoselective route to this antiobesity drug. We also presented a resolution method for preparation of the crucial intermediate, β- （t-butyldimethylsilyloxy）tetradecanal.展开更多
目的评价奥利司他治疗非酒精性脂肪性肝病的效果。方法从PubMed、Web of Science、中国知网、中国生物医学文献数据库、维普数据库和万方数据知识服务平台数据库检索从建库开始至2023年9月国内外关于奥利司他治疗非酒精性脂肪性肝病的...目的评价奥利司他治疗非酒精性脂肪性肝病的效果。方法从PubMed、Web of Science、中国知网、中国生物医学文献数据库、维普数据库和万方数据知识服务平台数据库检索从建库开始至2023年9月国内外关于奥利司他治疗非酒精性脂肪性肝病的文献。运用Review Manager 5.4.1进行Meta分析。结果研究共纳入8篇文献,共450例患者,纳入研究无发表偏倚。Meta分析结果显示,研究组患者为丙氨酸转氨酶(ALT)[MD=-35.18,95%CI(-56.71,-13.64),P<0.01],天冬氨酸转氨酶(AST)(MD=-25.69,95%CI(-43.13,-8.26),P<0.01],谷氨酰转移酶(GGT)[MD=-48.12,95%CI(-74.65,-21.60),P<0.01],总胆固醇[MD=-2.13,95%CI(-4.06,-0.21),P=0.03],三酰甘油[MD=-2.20,95%CI(-4.21,-0.19),P=0.03]水平低于对照组,差异均具有统计学意义。结论奥利司他治疗非酒精性脂肪性肝病可有效降低患者ALT、AST、GGT、总胆固醇及三酰甘油水平。展开更多
文摘Traditional treatment of type 2 diabetes mellitus (T2DM) has focused on correcting hyperglycemia. However, T2DM is almost always accompanied by other conditions and risk factors that affect its morbidity and mortality. Obesity represents one of the main risk factors associated in the T2DM and a modest weight loss around 5% is linked with significant reduction in the blood glucose levels. The objective of this study was to compare the pharmacokinetic parameters between two formulations of metformin, alone or combined with orlistat, in healthy volunteers. A single-blinded, single dose, two-period, two-sequence, crossover, randomized and balanced study design with a 7-day washout period was performed in 26 Mexican volunteers. Plasma samples were collected over a 24-hour period after administration of 500 mg metformin alone or combined with 60 mg orlistat in each period. A validated high-performance liquid chromatography coupled with a ultraviolet detector was used to analyze metformin concentration in plasma. Bioequivalence between metformin alone and metformin combined with orlistat was determined when the ratio for the 90% confidence intervals (CI) of area under the curve (AUC24h) and maximum concentration (Cmax) of the two formulations were within 80% and 125%. In the current study, the mean ± standard deviation (SD) of Cmax, AUC24h and AUC∞ of the formulation containing only metformin were 1.39 ± 0.44 μg/mL, 7.59 ± 3.17 μg h/mL and 8.48 ± 4.13 μg h/mL, respectively, while the mean ± SD of Cmax, AUC24h and AUC∞ of the formulation containing metformin and orlistat were 1.38 ± 0.48 μg/mL, 7.80 ± 2.83 μg h/mL and 9.13 ± 4.29 μg h/mL, respectively. The parametric 90% CI for Cmax and AUC24h were 87.5-109.3 and 88.7-124.7, respectively. These results suggest that both formulations are bioequivalent and there is not pharmacokinetic interaction between metformin and orlistat.
文摘Orlistat is a safe and effective drug to treat obesity by acting as a pancreatic and gastric lipase inhibitor, resulting in reduction in fat absorption. There is also concern that it may be linked with an increased threat of serious hepatic incidents. The present work was carried out to study the effect of orlistat on the histological, immunohistochemical and electron microscopic structure of the liver in the adult male albino rats and the possible protective role of β-carotene administration. Forty adult albino rats were subjected to experiment for two weeks as follows: group 1 (control), group II, each animal received 0.52 mg/kg bw/day β-Carotene, group III, each animal received orlistat 32 mg/kg/day, and group IV received β-Carotene, 1hour before the administration of orlistat at same dose of group II & III. The liver from each animal was dissected out and processed for histological, (light and electron microscopic study). The result of Hep-Par1 for immunohistochemistry was statistically analyzed. The results showed that orlistat treated group displayed variable disturbance of liver architecture, from dilatation, congested central and portal veins, branching of bile ductules, mononuclear cellular infiltration, areas of hemorrhages, cytoplasmic vacuolation and pyknotic nuclei. The most obvious changes were that degenerative changes in hepatocytes led to depletion of glycogen content of hepatocytes. Hep Par-1 revealed a wide area of negative immune expression around the central vein and in some hepatocytes. Other hepatocytes expressed weak reaction. Ultrastructure examination displayed hepatocytes with swollen mitochondria and others with an electron-dense matrix. The combined treatment of β-Carotene and orlistat led to a marked improvement in most of the previously mentioned changes. It was concluded that orlistat-induced hepatic toxicity. Thus, clinicians should cautiously monitor their patients for signs of hepatic dysfunction. Using an antioxidant such as β-Carotene decreased the toxicity of orlistat.
文摘Objectives To observe the influence of weight loss induced by orlistat on several cardiovascular diseases risk factors in obese Chinese subjects. Methods Sixty obese Chinese patients participated in a 24 week clinical trial. Participants were prescribed a slightly hypocaloric diet and exercise, then they were randomly assigned double -blind treatment with either orlistat 120 mg three times a day or placebo. Their body weight, blood pressure, fasting glucose, insulin, HbA1c, and serum lipid profile were performed before and after the weight loss intervention. Results After 24 weeks, orlistat -treated group lost more of their body weight than placebo group (6. 66 ± 0. 52 kg, 8. 44±4.08% and 1. 98 ± 0. 44 kg, 2. 44±1. 74 % , respectively, P < 0. 05) . Moreover, after treatment, orlistat - treated patients showed significant decreases in serum levels of total cholesterol, low density lipoprotein - cholesterol and high density lipoprotein - cholesterol ( P < 0.01), but in placebo group we found no change. Both systolic blood pressure and diastolic blood pressure fell significantly in orlistat - treated group. Fasting glucose and HOMA - IR in orlistat - treated group was distinctly reduced if compared with placebo group. Conclusions Weight loss resulting from orlistat treatment and slightly hypocaloric diet has produced favorable effects on several cardiovascular risk factors in obese Chinese subjects.
基金supported by grants from the National Natural Science Foundation of China(No.81672314)the Key Natural Science Project of Anhui Provincial Education Department(No.KJ2020A1244,KJ2020A0578,and KJ2018A0221)National Innovation Program for College Students(Nos.201810367021 and 201710367036).
文摘Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers,including lung cancer;however,targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need.In this study,we tested the anticancer activity of orlistat,an FDA-approved anti-obesity drug,in human and mouse cancer cells in vitro and in vivo,and we found that orlistat,as a single agent,inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro.Mechanistically,we found that orlistat reduced the expression of GPX4,a central ferroptosis regulator,and induced lipid peroxidation.In addition,we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2,a molecule regulating the lipid droplet homeostasis,as a novel target of orlistat.Moreover,in a mouse xenograft model,orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control(P<0.05).Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.
基金supported by the National Key Research and Development Program of China(No.2017YFC1001004)National Natural Science Foundation of China(No.81471428)Special Funds for Taishan Scholar Engineering,China(No.ts201712103).
文摘Polycystic ovary syndrome(PCOS)is a common gynecological endocrine syndrome characterized by metabolic abnormality and reproductive dysfunction,including ovulation abnormality,hyperandrogenism and polycystic ovarian manifestations.Most PCOS patients are overweight or obese,particularly the central type.This aggravates the clinical manifestations of PCOS and ultimately increases the risk of infertility.Orlistat is the only weight loss drug approved by the US Food and Drug Administration.As a long-lasting gastrointestinal lipase inhibitor,orlistat can effectively reduce the absorption of lipid and increase lipid excretion,thereby achieving weight loss.In obese PCOS patients,orlistat can reduce weight,improve lipid metabolism and insulin resistance,improve sex hormone disorder,and have a positive effect on pregnancy outcome.This review summarizes the impact of orlistat treatment on metabolism and fertility in obese women with PCOS.
文摘（-）-Tetrahydrolipstatin 1 was synthesized in three steps and 33.8% overall yield from aldehyde 6 by tandem Mukaiyama-aldol lactonization, which offered a concise, efficient and highly diastereoselective route to this antiobesity drug. We also presented a resolution method for preparation of the crucial intermediate, β- （t-butyldimethylsilyloxy）tetradecanal.
文摘目的评价奥利司他治疗非酒精性脂肪性肝病的效果。方法从PubMed、Web of Science、中国知网、中国生物医学文献数据库、维普数据库和万方数据知识服务平台数据库检索从建库开始至2023年9月国内外关于奥利司他治疗非酒精性脂肪性肝病的文献。运用Review Manager 5.4.1进行Meta分析。结果研究共纳入8篇文献,共450例患者,纳入研究无发表偏倚。Meta分析结果显示,研究组患者为丙氨酸转氨酶(ALT)[MD=-35.18,95%CI(-56.71,-13.64),P<0.01],天冬氨酸转氨酶(AST)(MD=-25.69,95%CI(-43.13,-8.26),P<0.01],谷氨酰转移酶(GGT)[MD=-48.12,95%CI(-74.65,-21.60),P<0.01],总胆固醇[MD=-2.13,95%CI(-4.06,-0.21),P=0.03],三酰甘油[MD=-2.20,95%CI(-4.21,-0.19),P=0.03]水平低于对照组,差异均具有统计学意义。结论奥利司他治疗非酒精性脂肪性肝病可有效降低患者ALT、AST、GGT、总胆固醇及三酰甘油水平。
