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Published on: February 9, 2022
Tyrphostin AG17 inhibits adipocyte differentiation in vivo and in vitro
Alberto Camacho1,2,3, Juan Carlos Segoviano-Ramírez4,5, Adriana Sánchez-Garcia6
1Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León (UANL), Monterrey, Mexico. acm590@hotmail.com.
Background:
Excessive subcutaneous adiposity in obesity is associated to positive white adipocyte tissue (WAT) differentiation (adipogenesis) and WAT expandability. Here, we hypothesized that supplementation with the insulin inhibitor and mitochondrial uncoupler, Tyrphostin (T-AG17), in vitro and in vivo inhibits adipogenesis and adipocyte hypertrophy.
Methods:
We used a 3T3-L1 proadipocyte cell line to identify the potential effect of T-AG17 on adipocyte differentiation and fat accumulation in vitro. We evaluated the safety of T-AG17 and its effects on physiological and molecular metabolic parameters including hormonal profile, glucose levels, adipogenesis and adipocyte hypertrophy in a diet-induced obesity model using C57BL/6 mice.
Results:
We found that T-AG17 is effective in preventing adipogenesis and lipid synthesis in the 3T3-L1 cell line, as evidenced by a significant decrease in oil red staining (p < 0.05). In obese C57BL/6 mice, oral administration of T-AG17 (0.175 mg/kg for 2 weeks) lead to decreased fat accumulation and WAT hypertrophy. Further, T-AG17 induced adipocyte apoptosis by activating caspase-3. In the hepatocytes of obese mice, T-AG17 promoted an increase in the size of lipid inclusions, which was accompanied by glycogen accumulation. T-AG17 did not alter serum biochemistry, including glucose, insulin, leptin, free fatty acids, creatinine, and aspartate aminotransferase.
Conclusion:
T-AG17 promotes adipocyte apoptosis in vivo and is an effective modulator of adipocyte differentiation and WAT hypertrophy in vitro and in vivo. Therefore, T-AG17 may be useful as a pharmacological obesity treatment.
Insights
Tyrphostin (T-AG17) effectively inhibits adipocyte differentiation and reduces fat accumulation in obesity models. This compound promotes adipocyte apoptosis, suggesting its potential as a novel pharmacological treatment for obesity.
Area of Science:
- Biochemistry
- Metabolic disease research
- Pharmacology
Background:
- Obesity is linked to increased white adipose tissue (WAT) differentiation and expansion.
- The insulin inhibitor and mitochondrial uncoupler Tyrphostin (T-AG17) was investigated for its effects on adipogenesis.
Purpose of the Study:
- To investigate the in vitro and in vivo effects of T-AG17 on adipocyte differentiation and hypertrophy.
- To evaluate T-AG17's safety and metabolic impact in a diet-induced obesity mouse model.
Main Methods:
- 3T3-L1 proadipocyte cell line used for in vitro differentiation studies.
- Diet-induced obesity model in C57BL/6 mice to assess T-AG17 effects on physiological and molecular parameters.
- Analysis included adipogenesis, lipid accumulation, apoptosis (caspase-3), and serum biochemistry.
Main Results:
- T-AG17 significantly inhibited adipogenesis and lipid synthesis in 3T3-L1 cells (p < 0.05).
- Oral T-AG17 administration in obese mice reduced fat accumulation and WAT hypertrophy.
- T-AG17 induced adipocyte apoptosis via caspase-3 activation and increased lipid/glycogen in hepatocytes without altering key serum markers.
Conclusions:
- T-AG17 effectively inhibits adipocyte differentiation and WAT hypertrophy in vitro and in vivo.
- T-AG17 promotes adipocyte apoptosis, indicating its potential as a pharmacological obesity treatment.
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