TNF-α modulates statin effects on secretion and expression of MCP-1, PAI-1 and adiponectin in 3T3-L1 differentiated adipocytes

Statin use is associated with increased calorie intake and consequent weight gain. It is speculated that statin‐dependent improvements in lipid profile may undermine the perceived need to follow lipid‐lowering and other dietary recommendations leading consequently to increased calorie intake. However, increases in calorie intake in statin users may also be related to statin‐dependent decreases in satiety factors such as leptin, an adipocyte‐derived adipokine. The objective of our study was to examine the direct effects of statins on leptin expression. Adipocytes are the main source of circulating leptin. Therefore, we examined the effects of atorvastatin and simvastatin on leptin expression in cultured human white adipocytes. We show that treatment of white adipocytes with simvastatin and atorvastatin decreases leptin mRNA expression (simvastatin: P = 0.008, atorvastatin: P = 0.03) and leptin secretion (simvastatin: P = 0.0001, atorvastatin: P = 0.0001). Both simvastatin and atorvastatin mediate decreases in leptin expression via extracellular‐signal‐regulated kinases 1/2 and peroxisome proliferator‐activated receptor gamma pathways (simvastatin: P = 0.01, atorvastatin: P = 0.026). Additionally, statin treatment also induced expected increases in adiponectin, while decreasing monocyte chemoattractant protein 1 (MCP1) mRNA. Furthermore, statins increased secretion of both total as well as high molecular weight adiponectin while decreasing MCP1 secretion. To conclude, statins act directly on human white adipocytes to regulate adipokine secretion and decrease leptin expression. Leptin is an important satiety factor. Hence, statin‐dependent decreases in leptin may contribute, at least in part, to increases in food intake in statin users.

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“…; Lobo et al. ; Krysiak et al. ), and are concordant with the pleiotropic anti‐inflammatory effect of statins.…”

Section: Discussionsupporting

confidence: 54%

“…; Lobo et al. ). Total RNA was isolated using PureLink RNA isolation kit (Ambion) and cDNA library was created using high‐capacity cDNA reverse transcription kit (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 98%

Statins decrease leptin expression in human white adipocytes

et al. 2018

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“…According to previous reports, TNF-α, methylenetetrahydrofolate reductase, ANXA1, and CRP were general causes of cerebral ischemia. [51][52][53][54] TNF-α is associated with increased plasminogen activator inhibitor-1 protein levels, 55 methylenetetrahydrofolate reductase dysfunction is related to plasma tHcy accumulation, 56 ANXA1 is connected to decreased TNF-α levels, 57 and CRP can elevate blood pressure, body mass index, insulin resistance, and triglycerides. 58 CRP and TNF-α are simultaneously activated in stress conditions.…”

Section: Discussionmentioning

confidence: 99%

Association of the miR-146a , miR-149 , miR-196a2 , and miR-499 Polymorphisms With Ischemic Stroke and Silent Brain Infarction Risk

Jeon

Kim

et al. 2013

ATVB

118

104

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Objective— MicroRNAs play a role in atherosclerosis-related diseases, such as cerebrovascular or cardiovascular disease. However, the effect of miR-146a , miR-149 , miR-196a2 , and miR-499 polymorphisms on stroke and silent brain infarction (SBI) susceptibility has not been reported. Methods and Results— Using polymerase chain reaction-amplified DNA, microRNA polymorphisms were analyzed in 678 patients with ischemic stroke, 373 patients with SBI, and 553 control subjects. The miR-146a C>G polymorphism and miR-146a G/ -149 T/ -196a2 C/ -499 G allele combination was significantly associated with ischemic stroke prevalence. For SBI prevalence, there were no statistically significant genetic markers. However, some allele combinations were associated with increased SBI incidence (C-T-C-G and G-T-T-A of miR-146a / -149 / -196a2 / -499 ). In subgroup analyses, miR-146a C>G increased stroke risk in female, normotensive, and nondiabetic groups. There were significant combined effects between microRNA polymorphisms and homocysteine/folate levels on ischemic stroke and SBI prevalence. Conclusion— The miR-146a G allele and miR-146a G/ -149 T/ -196a2 C/ -499 G allele combination were associated with ischemic stroke pathogenesis. The combined effects between microRNA polymorphisms and homocysteine/folate levels may contribute to stroke and SBI prevalence.

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“…Several explanations can be found in the literature to justify differences between gene and protein expression [48]–[51]: polysome activation on mRNA, alternative mRNA splicing, differences in the half-life of the protein and the mRNA, protein turnover, specific proteolytic processing. Moreover, additional factors regulate protein secretion: translocation across the plasma membrane, sequestration by secretory lysosomes, shedding of microvesicles at the extracellular side of the plasma membrane, etc [52].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Metabolites Modify Adipokine Expression and Secretion in 3T3-L1 Pre-Adipocytes and Mature Adipocytes

et al. 2013

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ObjectiveDue to the low bioavailability of resveratrol, determining whether its metabolites exert any beneficial effect is an interesting issue.Methods3T3-L1 maturing pre-adipocytes were treated during differentiation with 25 µM of resveratrol or with its metabolites and 3T3-L1 mature adipocytes were treated for 24 hours with 10 µM resveratrol or its metabolites. The gene expression of adiponectin, leptin, visfatin and apelin was assessed by Real Time RT-PCR and their concentration in the incubation medium was quantified by ELISA.ResultsResveratrol reduced mRNA levels of leptin and increased those of adiponectin. It induced the same changes in leptin secretion. Trans-resveratrol-3-O-glucuronide and trans-resveratrol-4′-O-glucuronide increased apelin and visfatin mRNA levels. Trans-resveratrol-3-O-sulfate reduced leptin mRNA levels and increased those of apelin and visfatin.ConclusionsThe present study shows for the first time that resveratrol metabolites have a regulatory effect on adipokine expression and secretion. Since resveratrol has been reported to reduce body-fat accumulation and to improve insulin sensitivity, and considering that these effects are mediated in part by changes in the analyzed adipokines, it may be proposed that resveratrol metabolites play a part in these beneficial effects of resveratrol.

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TNF-α modulates statin effects on secretion and expression of MCP-1, PAI-1 and adiponectin in 3T3-L1 differentiated adipocytes

Cited by 32 publications

References 30 publications

Statins decrease leptin expression in human white adipocytes

Statins decrease leptin expression in human white adipocytes

Association of the miR-146a , miR-149 , miR-196a2 , and miR-499 Polymorphisms With Ischemic Stroke and Silent Brain Infarction Risk

Resveratrol Metabolites Modify Adipokine Expression and Secretion in 3T3-L1 Pre-Adipocytes and Mature Adipocytes

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