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Rosiglitazone ameliorates palmitic acid-induced cytotoxicity in TM4 Sertoli cells
- Source :
- Reproductive Biology and Endocrinology, Vol 16, Iss 1, Pp 1-11 (2018), Reproductive Biology and Endocrinology : RB&E
- Publication Year :
- 2018
- Publisher :
- BMC, 2018.
-
Abstract
- The Sertoli cell is the only somatic cell within the seminiferous tubules, and is vital for testis development and spermatogenesis. Rosiglitazone (RSG) is a member of the thiazolidinedione family and is a peroxisome proliferator-activated receptor-γ (PPARγ) agonist. It has been reported that RSG protects various types of cells from fatty acid-induced damage. However, whether RSG serves a protective role in Sertoli cells against palmitic acid (PA)-induced toxicity remains to be elucidated. Therefore, the aim of the present study was to investigate the effect of RSG on PA-induced cytotoxicity in Sertoli cells. MTT assay and Oil Red O staining revealed that RSG ameliorated the PA-induced decrease in TM4 cell viability, which was accompanied by an alleviation of PA-induced lipid accumulation in cells. In primary mouse Sertoli cells, RSG also showed similar protective effects against PA-induced lipotoxicity. Knockdown of PPARγ verified that RSG exerted its protective role in TM4 cells through a PPARγ-dependent pathway. To evaluate the mechanism underlying the protective role of RSG on PA-induced lipotoxicity, the present study analyzed the effects of RSG on PA uptake, and the expression of genes associated with both fatty acid oxidation and triglyceride synthesis. The results demonstrated that although RSG did not affect the endocytosis of PA, it significantly elevated the expression of carnitine palmitoyltransferase (CPT)-1A, a key enzyme involved in fatty acid oxidation, which indicated that the protective effect of RSG may have an important role in fatty acid oxidation. On the other hand, the expression of CPT1B was not affected by RSG. Moreover, the expression levels of diacylglycerol O-acyltransferase (DGAT)-1 and DGAT2, both of which encode enzymes catalyzing the synthesis of triglycerides, were not suppressed by RSG. The results indicated that RSG reduced PA-induced lipid accumulation by promoting fatty acid oxidation mediated by CPT1A. The effect of RSG in protecting cells from lipotoxicity was also found to be specific to Sertoli cells and hepatocytes, and not to other cell types that do not store excess lipid in large quantities, such as human umbilical vein endothelial cells. These findings provide insights into the cytoprotective effects of RSG on Sertoli cells and suggest that PPARγ activation may be a useful therapeutic method for the treatment of Sertoli cell dysfunction caused by dyslipidemia. Electronic supplementary material The online version of this article (10.1186/s12958-018-0416-0) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Male
lcsh:QH471-489
medicine.drug_class
Cell Survival
Sertoli cells
Cytotoxicity
Gene Expression
lcsh:Gynecology and obstetrics
Cell Line
Rosiglitazone
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Palmitic acid
medicine
Oil Red O
Animals
Humans
Hypoglycemic Agents
lcsh:Reproduction
Viability assay
Thiazolidinedione
Beta oxidation
Cells, Cultured
lcsh:RG1-991
Diacylglycerol kinase
Mice, Inbred ICR
030219 obstetrics & reproductive medicine
Chemistry
Research
Obstetrics and Gynecology
Hep G2 Cells
Peroxisome
Sertoli cell
Lipid Metabolism
Cell biology
PPAR gamma
030104 developmental biology
medicine.anatomical_structure
Reproductive Medicine
Lipotoxicity
RNA Interference
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 14777827
- Volume :
- 16
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Reproductive Biology and Endocrinology
- Accession number :
- edsair.doi.dedup.....361c131912cde12bf108dbcfa3da216c