Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. It inhibits gastric and pancreatic lipases in the lumen of the gastrointestinal tract to decrease systemic absorption of dietary fat. Orlistat treatment also results in modest improvements in total cholesterol, low-density lipoprotein, blood pressure, and fasting glucose and insulin concentrations[3]. The use of orlistat has been associated with rare cases of acute kidney injury. Orlistat has a beneficial effect on carbohydrate metabolism. Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness[4]. Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract. An extremely low degree of systemic absorption for orlistat when administered with a hypocaloric, well-balanced diet with 20% to 30% of calories derived from fat (50-80 gm). Systemic absorption of orlistat is negligible; at a clinically efficacious dose level, orlistat is unlikely to produce systemic lipase inhibition[5]. When orlistat was administered in the early stage of AKT/c-Met-triggered hepatocarcinogenesis, it resulted in the elimination of hepatic tumor burden. Mechanistically, orlistat efficiently elevated PTEN expression and suppressed AKT/SREBP1/FASN (fatty acid synthase) signaling both in vivo and in vitro, impairing AKT/c-Met-driven de novo lipogenesis and aberrant proliferation[6].
Orlistat/奥利司他 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Huh7SR cells
102.67 ± 6.60 µM
24 hours
To evaluate the inhibitory effect of orlistat on the proliferation of Huh7SR cells, the results showed that orlistat significantly inhibited the proliferation of Huh7SR cells.
J Exp Clin Cancer Res. 2023 Jan 6;42(1):6.
7721SR cells
133.67 ± 6.56 µM
24 hours
To evaluate the inhibitory effect of orlistat on the proliferation of 7721SR cells, the results showed that orlistat significantly inhibited the proliferation of 7721SR cells.
J Exp Clin Cancer Res. 2023 Jan 6;42(1):6.
Huh7 cells
50 µM
48 hours
Enhanced the cytotoxicity of sorafenib, significantly increased the sub-G1 population
Int J Mol Sci. 2022 Jun 10;23(12):6501.
Huh7/SR cells
50 µM
48 hours
Enhanced the cytotoxicity of sorafenib, significantly increased the sub-G1 population
Int J Mol Sci. 2022 Jun 10;23(12):6501.
MS751 cells
100 µM and 250 µM
48 hours
To evaluate the effect of Orlistat on the proliferation of MS751 and SiHa cells, results showed that 100 μM and 250 μM Orlistat had no significant effect on cell viability but significantly inhibited FABP5-induced FA metabolic reprogramming, invasion, EMT, and lymphangiogenesis.
Theranostics. 2020 May 17;10(15):6561-6580.
SiHa cells
100 µM and 250 µM
48 hours
To evaluate the effect of Orlistat on the proliferation of SiHa cells, results showed that 100 μM and 250 μM Orlistat had no significant effect on cell viability but significantly inhibited FABP5-induced FA metabolic reprogramming, invasion, EMT, and lymphangiogenesis.
Theranostics. 2020 May 17;10(15):6561-6580.
Orlistat/奥利司他 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague-Dawley rats
High-fat diet-induced obesity model
Oral gavage
10 mg/kg
Single dose, observed for 48 hours
To evaluate the inhibitory effect of Orlistat on fat absorption, results showed that the SSPH6 group had significantly higher fat excretion than the control and Orlistat groups
Int J Nanomedicine. 2018 Nov 5;13:7095-7106
BALB/c mice
AOM/DSS-induced colitis-associated colon cancer model
Oral
10 mg/kg/day
Once daily for one week
Orlistat significantly increased the survival rate, reduced tumor formation, and inhibited inflammation, hyperplasia, and tumor progression in WD-driven CAC mice by suppressing STAT3 and NF-κB signaling pathways.
Cells. 2021 Aug 11;10(8):2060
Nude mice
Liver cancer model
Gavage
240 mg/kg
5 days/week for 21 days
To evaluate the antitumor effect of orlistat in a liver cancer model, the results showed that orlistat significantly inhibited tumor growth.
J Exp Clin Cancer Res. 2023 Jan 6;42(1):6.
BALB/c Nude mice
LNM model
Intraperitoneal injection
240 mg/kg/d
Once daily for 25 days
To evaluate the effect of Orlistat on FABP5-induced LNM, results showed that Orlistat significantly inhibited FABP5-induced LNM and reversed FA metabolic reprogramming.
Theranostics. 2020 May 17;10(15):6561-6580.
C57BL/6 mice
H22 tumor model
Intraperitoneal injection
5 mg/kg
Once on the first day and then every 4 days thereafter
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