Differential inhibition of lipolysis by 2-bromopalmitic acid and 4-bromocrotonic acid in 3T3-L1 adipocytes
| Autor: | Jim C. Fong, Shr Jeng Jim Leu, Shin Pei Chai |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_specialty
Lipolysis Palmitates Biophysics Hormone-sensitive lipase Biochemistry Differential inhibition Mice chemistry.chemical_compound Endocrinology Internal medicine Adipocyte Adipocytes medicine Animals Enzyme Inhibitors Lipase Beta oxidation 4-bromocrotonic acid Dose-Response Relationship Drug biology Fatty Acids Isoproterenol 3T3-L1 3T3 Cells Sterol Esterase Bucladesine chemistry Crotonates biology.protein |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 1344:65-73 |
| ISSN: | 0005-2760 |
| DOI: | 10.1016/s0005-2760(96)00133-6 |
| Popis: | Two inhibitors of fatty acid oxidation, 2-bromopalmitic acid (Br-C16) and 4-bromocrotonic acid (Br-C4) were examined for their effect on lipolysis in 3T3-L1 adipocytes. Both agents inhibited in a dose-dependent manner the rate of oxidation of exogenously added [1-14C]palmitate with similar time-courses, reaching a plateau at 3–9 h. While Br-C16 at 50 μM and 100 μM inhibited palmitate oxidation by approximately 40% and 60%, respectively, pretreatment with both concentrations inhibited lipolysis in washed cells in an almost identical manner. The magnitude of inhibition increased with time of pretreatment. On the other hand, like inhibition of fatty acid oxidation, inhibition of lipolysis by Br-C4 pretreatment was dose-dependent with maximal inhibition reached after 3 h pretreatment. The finding that isoproterenol- and dibutyryl cAMP-stimulated lipolysis were similarly suppressed by either Br-C4 or Br-C16 pretreatment, suggesting that a step distal to cAMP formation was involved. In addition, while the inhibitory effect of Br-C16 was not significantly influenced, the inhibition of lipolysis caused by Br-C4 was attenuated by pretreating cells with crotonic acid, octanoate, or palmitate. The longer chain-length of the fatty acids the cells were exposed, the stronger attenuation of the inhibition caused by Br-C4 was observed. Moreover, whereas pretreatment with Br-C16 was without effect, pretreatment with Br-C4 significantly decreased hormone-sensitive lipase (HSL) activity in cell extracts, albeit to an extent much smaller than its inhibitory effect on lipolysis. In conclusion, these results indicate that irreversible inhibition of lipolysis by Br-C16 or Br-C4 cannot be attributed to their effect on fatty acid oxidation. Some factor capable of modulating HSL activity seems to be involved. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect