Role of dipeptidyl peptidase IV (DPP4) in the development of dyslipidemia: DPP4 contributes to the steroid metabolism pathway
| Autor: | Youichi Sato, Sakura Koshioka, Takayuki Kamimoto, Yutaka Nakahori, Kazuyoshi Kawazoe, Kazuo Minakuchi, Shinji Abe, Yasushi Kirino |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty 17-Hydroxysteroid Dehydrogenases Dipeptidyl Peptidase 4 Streptozocin General Biochemistry Genetics and Molecular Biology Dipeptidyl peptidase Cell Line Estradiol Dehydrogenases Sterol 14-Demethylase chemistry.chemical_compound Internal medicine medicine Animals Humans General Pharmacology Toxicology and Pharmaceutics Dyslipidemias Oligonucleotide Array Sequence Analysis biology Reverse Transcriptase Polymerase Chain Reaction Cholesterol nutritional and metabolic diseases Cytochrome P450 Lipid metabolism General Medicine Lipid Metabolism medicine.disease Streptozotocin Rats Inbred F344 Rats Endocrinology Liver chemistry Sex steroid biology.protein Hydroxysteroid Dyslipidemia medicine.drug |
| Zdroj: | Life Sciences. 88:43-49 |
| ISSN: | 0024-3205 |
| Popis: | Aims We previously reported that dipeptidyl peptidase IV (DPP4)-deficient rats were susceptible to dyslipidemia induced by streptozotocin (STZ). Hence, it is suggested that DPP4 is important for lipid metabolism. Main methods In this study, to verify the role of DPP4 in the development of dyslipidemia, we carried out a microarray analysis of the livers of STZ-treated wild-type and DPP4-deficient rats and showed that the expression levels of genes involved in metabolic processes (steroid metabolic processes and cellular lipid metabolic processes) were significantly altered by STZ treatment. Key findings In the wild-type rats, the expression of hydroxysteroid (17-beta) dehydrogenase 2 ( Hsd7b2 ), which catalyzes sex steroid synthesis from cholesterol, was significantly increased by about 15-fold after STZ treatment; however, it did not change in the DPP4-deficient rats. In the STZ untreated group of DPP4-deficient rats, the expression levels of cytochrome P450, subfamily 51 ( Cyp51 ) and sterol-C4-methyl oxidase-like ( Sc4mol ), which catalyze intermediate steps in cholesterol synthesis, were significantly elevated compared to those of other groups. Similar results were demonstrated in HuH7-cells after DPP4 overexpression or the addition of human sera containing DPP4. Significance DPP4 is crucial for regulating the expression of factors related to steroid metabolism such as Cyp51, Sc4mol, and Hsd17b2, and DPP4 deficiency or inhibition may cause dyslipidemia. |
| Databáze: | OpenAIRE |
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