The combination of plant-derived compounds with anti-diabetic agents to manage hepatic steatosis closely associated with diabetes mellitus may be a new therapeutic approach. Silymarin, a complex of bioactive substances extracted from Silybum marianum, evinces an antioxidative, anti-inflammatory, and hepatoprotective activity. In this study, we investigated whether metformin (300 mg/kg/day for four weeks) supplemented with micronized silymarin (600 mg/kg/day) would be effective in mitigating fatty liver disturbances in a pre-diabetic model with dyslipidemia. Compared with metformin monotherapy, the metformin-silymarin combination reduced the content of neutral lipids (TAGs) and lipotoxic intermediates (DAGs). Hepatic gene expression of enzymes and transcription factors involved in lipogenesis (Scd-1, Srebp1, Pparγ, and Nr1h) and fatty acid oxidation (Pparα) were positively affected, with hepatic lipid accumulation reducing as a result. Combination therapy also positively influenced arachidonic acid metabolism, including its metabolites (14,15-EET and 20-HETE), mitigating inflammation and oxidative stress. Changes in the gene expression of cytochrome P450 enzymes, particularly Cyp4A, can improve hepatic lipid metabolism and moderate inflammation. All these effects play a significant role in ameliorating insulin resistance, a principal background of liver steatosis closely linked to T2DM. The additive effect of silymarin in metformin therapy can mitigate fatty liver development in the pre-diabetic state and before the onset of diabetes.

• Klíčová slova
• combination therapy, liver steatosis, metformin, pre-diabetes, silymarin,
• Publikační typ
• časopisecké články MeSH

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

Hypolipidemic and cardioprotective effects of statins can be associated with the development of myopathies and new-onset type 2 diabetes. These adverse effects may be related to increased oxidative stress. The plant extract silymarin (SM) is known for its antioxidant and anti-inflammatory actions. We tested the hypothesis that the combination of atorvastatin (ATV) with SM could improve therapy efficacy and eliminate some negative effects of statin on hypertriglyceridemia-induced metabolic disorders. Hereditary hypertriglyceridemic rats were fed a standard diet for four weeks without supplementation; supplemented with ATV (5 mg/kg b. wt./day) or a combination of ATV with 1 % micronized SM (ATV+SM). ATV treatment elevated plasma levels of HDL-cholesterol (p<0.01), glucose and insulin and decreased triglycerides (p<0.001). The combination of ATV+SM led to a significant reduction in insulin, an improvement of glucose tolerance, and the hypolipidemic effect was enhanced compared to ATV alone. Furthermore, ATV supplementation increased skeletal muscle triglycerides but its combination with SM decreased triglycerides accumulation in the muscle (p<0.05) and the liver (p<0.01). In the liver, ATV+SM treatment increased the activities of antioxidant enzymes, glutathione and reduced lipid peroxidation (p<0.001). The combined administration of ATV with SM potentiated the hypolipidemic effect, reduced ectopic lipid accumulation, improved glucose metabolism, and increased antioxidant and anti-inflammatory actions. Our results show that SM increased the effectiveness of statin therapy in a hypertriglyceridemic rat model of metabolic syndrome.

• MeSH
• anticholesteremika škodlivé účinky   MeSH
• antioxidancia farmakologie   MeSH
• atorvastatin škodlivé účinky   MeSH
• diabetes mellitus 2. typu chemicky indukované   farmakoterapie   patologie   MeSH
• hypercholesterolemie krev   MeSH
• hyperlipidemie farmakoterapie   MeSH
• kombinovaná farmakoterapie MeSH
• krysa rodu Rattus MeSH
• metabolický syndrom farmakoterapie   genetika   patologie   MeSH
• modely nemocí na zvířatech MeSH
• oxidační stres účinky léků   MeSH
• silymarin farmakologie   MeSH
• triglyceridy krev   MeSH
• zánět farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anticholesteremika MeSH
• antioxidancia MeSH
• atorvastatin MeSH
• silymarin MeSH
• triglyceridy MeSH