Atglistatin

Atglistatin inhibits lipolysis in cell and organ cultures by targeting ATGL with no cytotoxicity up to a concentration of 50 μM. ^[1]

In vivo, Atglistatin (i.p.) results in Dose and time-dependent inhibition of lipolysis. Oral treatment of Atglistatin causes a dose-dependent decrease in FA of up to 50% and 62%, respectively, and also causes a strong reduction in plasma TG levels (43%). In addition, Atglistatin shows a distinct tissue distribution and primarily accumulates in liver and adipose tissue. ^[1]

• Determination of lipase activity

  For determination of lipase activity, lysates are incubated with a substrate containing radiolabeled [9,10-3H(N)]-triolein. Subsequently, FA are extracted and quantitated by liquid scintilation counting. Data are presented as mean ?S.D. of triplicate determinations and representative for at least three independent experiments.

• Cell lines

  AML-12 mouse hepatocytes

• Concentrations

  ~50 μM

• Incubation Time

  2 hours

• Method

  For MTT-based in vitro viability assays, cells are seeded in 96-well plates and cultured under standard conditions for 24 h. The next day, cells are pretreated with different concentrations of Atglistatin dissolved in DMSO or dissolved in DMF as positive control for 2 h. Medium is replaced by an identical fresh medium and incubated again for the indicated time points. Thereafter, cells are incubated for 3 h with 100 μL Thiazolyl Blue Tetrazolium Bromide (MTT). The resulting violet formazan crystals are dissolved by adding 100 μL of MTT solubilization solution (0.1% NP-40, 4 mM HCl and anhydrous isopropanol). After complete dissolution of the formazan product, absorbance is measured at 595 nm using 690 nm as reference wavelength.

• Animal Models

  Mice (C57Bl/6J)

• Dosages

  1.4 mg/mouse (oral gavage); ~400 μmol/kg (i.p.)

• Administration

  oral gavage or i.p.