Short and long term in vivo effects of Cyclosporine A and Sirolimus on genes and proteins involved in lipid metabolism in Wistar rats

Lopes, Pedro; Fuhrmann, Amelia; Espinoza, Daniel; Pereira, Maria J.; Eriksson, Jan W.; Reis, Flávio; Carvalho, Eugénia

doi:10.1016/j.metabol.2014.02.004

Cited by 19 publications

(7 citation statements)

References 47 publications

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“…First, it was reported that humans and animal models treated with rapamycin show a significant elevation in circulating free fatty acids (2,40,86). Consistently, isolated adipocytes exposed to rapamycin exhibit higher basal and isoproterenol-stimulated lipolysis ex vivo (14,77,99). A similar effect was also observed in mature 3T3-L1 cells treated with rapamycin or depleted from Raptor (14,121).…”

Section: Mtorc1mentioning

confidence: 75%

“…As mentioned above, treatment of mice or adipose cells with rapamycin promotes triglyceride breakdown and the release of free fatty acids (2,14,40,77,86,99,121). Although there are indications that mTORC1 per se can affect lipolysis (14,15), the possibility that rapamycin could indirectly affect this process by modulating mTORC2 function should not be ruled out.…”

Section: Lipolysis and Mtor Signaling: The Picture Is Still Not Perfementioning

confidence: 99%

“…One study in rats suggests that this is effectively the case (40). Unfortunately, the impact of rapamycin on mTORC2 function was not assessed in most of the studies cited above (2,14,77,86,99,121). Although genetic evidence supports a direct role for mTORC1 in the control of adipocyte lipolysis (14), adipose-specific deletion of Raptor in mice does not affect lipolysis (101).…”

Section: Lipolysis and Mtor Signaling: The Picture Is Still Not Perfementioning

confidence: 99%

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The Roles of mTOR Complexes in Lipid Metabolism

2015

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The synthesis of lipids in response to food intake represents a key advantage that allows organisms to survive when energy availability is limited. In mammals, circulating levels of insulin and nutrients, which fluctuate between fasting and feeding, dictate whether lipids are synthesized or catabolized by tissues. The mechanistic target of rapamycin (mTOR), a kinase that is activated by anabolic signals, plays fundamental roles in regulating lipid biosynthesis and metabolism in response to nutrition. The mTOR kinase nucleates two large protein complexes named mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Following their activation, these complexes facilitate the accumulation of triglycerides by promoting adipogenesis and lipogenesis and by shutting down catabolic processes such as lipolysis and β-oxidation. Here, we review and discuss the roles of mTOR complexes in various aspects of lipid metabolism in mammals. We also use this opportunity to discuss the implication of these relations to the maintenance of systemic lipid homeostasis.

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Section: Mtorc1mentioning

confidence: 75%

Section: Lipolysis and Mtor Signaling: The Picture Is Still Not Perfementioning

confidence: 99%

Section: Lipolysis and Mtor Signaling: The Picture Is Still Not Perfementioning

confidence: 99%

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The Roles of mTOR Complexes in Lipid Metabolism

2015

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“…It has been suggested that sirolimus exerts detrimental effects on host metabolism through inhibition of the mTOR pathway. 3-5 In addition, hyperlipidemia is one of the most exacerbated adverse effects of mTOR inhibitors. 6 In early clinical trials, approximately 50% of sirolimus-administered patients presented with hyperlipidemia (either hypercholesterolemia or hypertriglyceridemia).…”

Section: Introductionmentioning

confidence: 99%

Intestinal Dysbiosis Correlates With Sirolimus-induced Metabolic Disorders in Mice

Han

Ling

et al. 2020

Transplantation

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“…Although the pathogenesis of dyslipidemia in SLE has not been clearly identified, many evidences support the hypothesis that several drugs commonly used in SLE patients induce undesirable effects on lipid metabolism, such as corticosteroids [ 7 ], cyclosporine A [ 8 ], and tacrolimus [ 9 ]. On the other hand, immune response and metabolic regulation are highly integrated.…”

Section: Introductionmentioning

confidence: 99%

Dyslipidemia is associated with inflammation and organ involvement in systemic lupus erythematosus

et al. 2023

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Introduction Disturbed lipid metabolism was observed in systemic lupus erythematosus (SLE) patients. This study aimed to evaluate the relationships between dyslipidemia and visceral organ involvement, disease severity, inflammatory factors, and drug intake in SLE patients. Method Inpatients with SLE (n = 105) and healthy controls (HC) (n = 75) were recruited in this study. Clinical and laboratory data were collected from patient records. The concentrations of tumor necrosis factor receptors superfamily member1A (TNFRSF1A), member1B (TNFRSF1B) and adipokine angiopoietin-like 4 (ANGPTL4) in plasma were measured by ELISA. Result Compared to HC, serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and apolipoprotein B (ApoB) were significantly increased, while high-density lipoprotein (HDL) and apolipoprotein A1 (ApoA1) were decreased in SLE patients. Patients with higher disease activity and renal damage suffered from more severe dyslipidemia. Renal functional parameters were closely correlated with serum lipid levels. Inflammatory factors were associated with dyslipidemia. The levels of TNFRSF1A and TNFRSF1B were obviously increased and associated with kidney involvement in SLE patients. Patients with high-dose glucocorticoid intake showed more severe dyslipidemia. Conclusions Attention should be paid to the dyslipidemia of SLE. Dyslipidemia is associated with inflammation and organ involvement in SLE. These findings might provide a new strategy for the treatment of SLE. Key Points• Serum levels of TG, TC, LDL, and ApoB were significantly increased, while HDL and ApoA1 were decreased in SLE patients.• Patients with higher disease activity and renal damage suffered from more severe dyslipidemia. Renal functional parameters and inflammatory factors were closely correlated with serum lipid levels.• Patients with high-dose glucocorticoid intake showed more severe dyslipidemia.• These findings might provide a new strategy for the treatment of SLE.

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Short and long term in vivo effects of Cyclosporine A and Sirolimus on genes and proteins involved in lipid metabolism in Wistar rats

Cited by 19 publications

References 47 publications

The Roles of mTOR Complexes in Lipid Metabolism

The Roles of mTOR Complexes in Lipid Metabolism

Intestinal Dysbiosis Correlates With Sirolimus-induced Metabolic Disorders in Mice

Dyslipidemia is associated with inflammation and organ involvement in systemic lupus erythematosus

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