Nejvíce citovaný článek - PubMed ID 14640889
Transgenic expression of CD36 in the spontaneously hypertensive rat is associated with amelioration of metabolic disturbances but has no effect on hypertension
Ovarian hormone deficiency leads to increased body weight, visceral adiposity, fatty liver and disorders associated with menopausal metabolic syndrome. To better understand the underlying mechanisms of these disorders in their early phases of development, we investigated the effect of ovariectomy on lipid and glucose metabolism. Compared to sham-operated controls, ovariectomized Wistar female rats markedly increased whole body and visceral adipose tissue weight (p ˂ 0.05) and exhibited insulin resistance in peripheral tissues. Severe hepatic triglyceride accumulation (p ˂ 0.001) after ovariectomy preceded changes in both serum lipids and glucose intolerance, reflecting alterations in some CYP proteins. Increased CYP2E1 (p ˂ 0.05) and decreased CYP4A (p ˂ 0.001) after ovariectomy reduced fatty acid oxidation and induced hepatic steatosis. Decreased triglyceride metabolism and secretion from the liver contributed to hepatic triglyceride accumulation in response to ovariectomy. In addition, interscapular brown adipose tissue of ovariectomized rats exhibited decreased fatty acid oxidation (p ˂ 0.01), lipogenesis (p ˂ 0.05) and lipolysis (p ˂ 0.05) despite an increase in tissue weight. The results provide evidence that impaired hepatic triglycerides and dysregulation of some CYP450 proteins may have been involved in the development of hepatic steatosis. The low metabolic activity of brown adipose tissue may have contributed to visceral adiposity as well as triglyceride accumulation during the postmenopausal period.
- Klíčová slova
- brown adipose tissue, hepatic steatosis, insulin resistance, metabolic syndrome, methylglyoxal, obesity, ovariectomy,
- MeSH
- bílá tuková tkáň metabolismus MeSH
- dieta s vysokým obsahem tuků MeSH
- dyslipidemie metabolismus MeSH
- glukosa metabolismus MeSH
- hmotnostní přírůstek MeSH
- hnědá tuková tkáň metabolismus MeSH
- inzulin metabolismus MeSH
- inzulinová rezistence MeSH
- játra metabolismus MeSH
- krysa rodu Rattus MeSH
- lipidy krev MeSH
- lipogeneze účinky léků MeSH
- lipolýza MeSH
- menopauza metabolismus fyziologie MeSH
- metabolismus lipidů účinky léků fyziologie MeSH
- nitrobřišní tuk metabolismus MeSH
- obezita metabolismus MeSH
- ovarektomie škodlivé účinky MeSH
- poruchy metabolismu lipidů etiologie patofyziologie MeSH
- postmenopauza metabolismus fyziologie MeSH
- potkani Wistar MeSH
- systém (enzymů) cytochromů P-450 metabolismus fyziologie MeSH
- triglyceridy metabolismus MeSH
- ztučnělá játra metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- glukosa MeSH
- inzulin MeSH
- lipidy MeSH
- systém (enzymů) cytochromů P-450 MeSH
- triglyceridy MeSH
Hypertension, dyslipidemia, and insulin resistance in the spontaneously hypertensive rat (SHR) can be alleviated by rescuing CD36 fatty acid translocase. The present study investigated whether transgenic rescue of CD36 in SHR could affect mitochondrial function and activity of selected metabolic enzymes in the heart. These analyses were conducted on ventricular preparations derived from SHR and from transgenic strain SHR-Cd36 that expresses a functional wild-type CD36. Our respirometric measurements revealed that mitochondria isolated from the left ventricles exhibited two times higher respiratory activity than those isolated from the right ventricles. Whereas, we did not observe any significant changes in functioning of the mitochondrial respiratory system between both rat strains, enzyme activities of total hexokinase, and both mitochondrial and total malate dehydrogenase were markedly decreased in the left ventricles of transgenic rats, compared to SHR. We also detected downregulated expression of the succinate dehydrogenase subunit SdhB (complex II) and 70 kDa peroxisomal membrane protein in the left ventricles of SHR-Cd36. These data indicate that CD36 may affect in a unique fashion metabolic substrate flexibility of the left and right ventricles.
- Klíčová slova
- CD36, Heart, Left and right ventricles, Mitochondria, OXPHOS, SHR,
- MeSH
- ABC transportéry genetika metabolismus MeSH
- antigeny CD36 genetika metabolismus MeSH
- exprese genu MeSH
- hexokinasa genetika metabolismus MeSH
- hypertenze enzymologie genetika patofyziologie MeSH
- inzulinová rezistence MeSH
- kardiomyocyty enzymologie patologie MeSH
- krysa rodu Rattus MeSH
- malátdehydrogenasa genetika metabolismus MeSH
- mitochondrie enzymologie patologie MeSH
- oxidativní fosforylace MeSH
- potkani inbrední SHR MeSH
- potkani transgenní MeSH
- primární buněčná kultura MeSH
- regulace genové exprese MeSH
- spotřeba kyslíku genetika MeSH
- srdeční komory enzymologie patologie MeSH
- sukcinátdehydrogenasa genetika metabolismus MeSH
- transgeny * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ABC transportéry MeSH
- Abcd3 protein, rat MeSH Prohlížeč
- antigeny CD36 MeSH
- hexokinasa MeSH
- malátdehydrogenasa MeSH
- sukcinátdehydrogenasa MeSH