Atglistatin targets the triacylglycerol (TG) hydrolase activity of adipose triglyceride lipase (ATGL) in white adipose tissue (WAT), inhibiting it in a dose-dependent manner and achieving up to a 78% reduction at the highest tested concentration. In WAT lysates from ATGL knockout (ko) animals, where TG hydrolase activity is already diminished by about 70%, Atglistatin exerts a moderate effect on the remaining activity. This suggests that the majority of the non-ATGL related TG hydrolase activity can be attributed to hormone-sensitive lipase (HSL), especially since the combined inhibition with Atglistatin and an HSL inhibitor nearly abolishes TG hydrolase activity in WAT (-95%)[1].
体内研究
Administered orally in olive oil, Atglistatin influences plasma and tissue TG levels, among other metabolic parameters, in animals. Lipolytic indicators such as fatty acids (FA) and glycerol show reductions 4 and 8 hours post-administration, with levels returning to baseline after 12 hours. A dose-dependent decrease in FA and glycerol, up to 50% and 62% respectively, is observed 8 hours following treatment. Additionally, Atglistatin significantly lowers plasma TG levels by 43% without affecting blood glucose, total cholesterol, ketone bodies, and insulin levels. These effects are also seen when Atglistatin is administered via intraperitoneal injection, highlighting its potential as an anti-lipolytic agent[1].
体外研究
Atglistatin targets the triacylglycerol (TG) hydrolase activity of adipose triglyceride lipase (ATGL) in white adipose tissue (WAT), inhibiting it in a dose-dependent manner and achieving up to a 78% reduction at the highest tested concentration. In WAT lysates from ATGL knockout (ko) animals, where TG hydrolase activity is already diminished by about 70%, Atglistatin exerts a moderate effect on the remaining activity. This suggests that the majority of the non-ATGL related TG hydrolase activity can be attributed to hormone-sensitive lipase (HSL), especially since the combined inhibition with Atglistatin and an HSL inhibitor nearly abolishes TG hydrolase activity in WAT (-95%)[1].
Atglistatin 细胞实验
Cell Line
Concentration
Treated Time
Description
References
SGBS adipocytes
50 µM
1 hour
Atglistatin failed to inhibit FA release from SGBS adipocytes.
Nat Commun. 2017 Mar 22;8:14859.
3T3-L1 adipocytes
0, 0.1, 1, 10, 50 µM
Atglistatin inhibits lipolysis by targeting ATGL
Nat Chem Biol. 2013 Dec;9(12):785-7.
HL-1 cardiomyocytes
40 mM
1 hour
Atglistatin significantly blocked the release of specific fatty acids that induced pro-apoptotic effects in cardiomyocytes.
Cardiovasc Res. 2022 Aug 24;118(11):2488-2505.
3T3-L1 adipocytes
50 µM
1 hour
Atglistatin effectively inhibited the release of FA from murine 3T3-L1 adipocytes by 98%.
Nat Commun. 2017 Mar 22;8:14859.
Cardiomyocytes
10 µM
Atglistatin attenuated the PEDF or 44mer-induced TG lipolysis activation of cardiomyocytes.
J Transl Med. 2015 Feb 21;13:68.
Atglistatin 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
iCMp38αKO
Oral
0.4 mg/g
2 days prior to AngII treatment and continued for 48 h thereafter
Inhibition of lipolysis improved cardiac outcomes and reduced neutrophil numbers.
Basic Res Cardiol. 2022 Oct 7;117(1):48
Mice
Glucocorticoid-induced metabolic syndrome model
Diet
2 g/kg diet
For two weeks
Inhibiting lipolysis reduced glucocorticoid-induced fat mass gain, insulin resistance, and hyperglycemia
Mol Metab. 2023 Aug;74:101751
Mice
Catecholamine-induced cardiac damage
Oral
2 mmol/kg
5 days prior to ISO application
Atglistatin treatment led to a dramatic reduction of pro-fibrotic and pro-apoptotic processes, improving cardiac function.
Cardiovasc Res. 2022 Aug 24;118(11):2488-2505.
Mice
HFD-induced obesity model
Oral
2 mmol/kg diet
Daily for 50 days
Atglistatin effectively reduces adipose tissue lipolysis, weight gain, IR and NAFLD in mice fed a high-fat diet.
Nat Commun. 2017 Mar 22;8:14859.
C57BL/6J mice
Wild-type and ATGL-deficient (ATGL-ko) mice
Oral gavage
200 μmol/kg
Single dose; Blood and tissues were collected after 8 hours
Atglistatin showed a dose-dependent decrease in FA and glycerol levels
Nat Chem Biol. 2013 Dec;9(12):785-7.
Mice
Ghrelin-deficient mice
Intraperitoneal injection
50 μg/g
Single injection
Atglistatin inhibited IGF-1-induced lipolysis in adipose tissue, blocking the increases in plasma glycerol and free fatty acids, and also blocking the increase in hepatic triglycerides, indicating that IGF-1 raises blood glucose by stimulating adipose tissue lipolysis.
Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2208855119
Mice
Goat/C0//C0 mice
Intraperitoneal injection
50 μg/g
Single injection
Atglistatin inhibited IGF-1-induced lipolysis, blocking the increase in plasma glycerol and free fatty acids, and also blocking the increase in hepatic triglycerides, thereby preventing the IGF-1-mediated increase in blood glucose.
Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2208855119
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