Immunosuppressive agents (IAs) |
Calcineurin inhibitors |
Cyclosporin A (CsA) |
- Impairs glucose tolerance and increases lipolysis of both human and rodent adipocytes - Increases adipocyte weight and diameter - Removes GLUT4 from the cell surface of differentiated human adipocytes via an increased rate of endocytosis |
Lopes et al. 2013LOPES P, FUHRMANN A, SERENO J, PEREIRA MJ, NUNES P, PEDRO J, MELÃO A, REIS F & CARVALHO E. 2013. Effects of Cyclosporine and Sirolimus on Insulin-Stimulated Glucose Transport and Glucose Tolerance in a Rat Model. Transplant Proc 45(3): 1142-1148., Lopes et al. 2014aLOPES PC, FUHRMANNA A, SERENOB J, ESPINOZA DO, PEREIRA MJ, ERIKSSON JW, REIS F & CARVALHO E. 2014a. Short and long term in vivo effects of Cyclosporine A and Sirolimus on genes and proteins involved in lipid metabolism in Wistar rats. Metab Clin Exp 63(5): 702-715., Pereira et al. 2013PEREIRA MJ, PALMING J, RIZELL M, AURELIANO M, CARVALHO E, SVENSSON MK & ERIKSSON JW. 2013. The immunosuppressive agents rapamycin, cyclosporin A and tacrolimus increase lipolysis, inhibit lipid storage and alter expression of genes involved in lipid metabolism in human adipose tissue. Mol Cell Endocrinol 365(2): 260-269., Pereira et al. 2014PEREIRA MJ, PALMING J, RIZELL M, AURELIANO M, CARVALHO E, SVENSSON MK & ERIKSSON JW. 2014. Cyclosporine A and tacrolimus reduce the amount of GLUT4 at the cell surface in human adipocytes: Increased endocytosis as a potential mechanism for the diabetogenic effects of immunosuppressive agents. J Clin Endocrinol Metab 99(10): E1885-94.
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Tacrolimus (Tac) |
- Increases lipolysis and inhibits lipid storage in isolated human adipocytes and/or adipose tissue - Removes GLUT4 from the cell surface of differentiated human adipocytes via an increased rate of endocytosis |
Pereira et al. 2013PEREIRA MJ, PALMING J, RIZELL M, AURELIANO M, CARVALHO E, SVENSSON MK & ERIKSSON JW. 2013. The immunosuppressive agents rapamycin, cyclosporin A and tacrolimus increase lipolysis, inhibit lipid storage and alter expression of genes involved in lipid metabolism in human adipose tissue. Mol Cell Endocrinol 365(2): 260-269., Pereira et al. 2014PEREIRA MJ, PALMING J, RIZELL M, AURELIANO M, CARVALHO E, SVENSSON MK & ERIKSSON JW. 2014. Cyclosporine A and tacrolimus reduce the amount of GLUT4 at the cell surface in human adipocytes: Increased endocytosis as a potential mechanism for the diabetogenic effects of immunosuppressive agents. J Clin Endocrinol Metab 99(10): E1885-94.
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Rapamycin (RAPA) = Sirolimus (SRL) |
- Impairs glucose tolerance and increases lipolysis in human adipocytes or in isolated rodent adipocytes in WAT - Reduces the phosphorylation and/or protein levels of the insulin signaling proteins of both human and rodent adipocytes - Inhibits lipolysis, alters mitochondrial bioenergetics and reduces thermogenesis in BAT of the rats |
Lopes el at. 2013, Lopes et al. 2014aLOPES PC, FUHRMANNA A, SERENOB J, ESPINOZA DO, PEREIRA MJ, ERIKSSON JW, REIS F & CARVALHO E. 2014a. Short and long term in vivo effects of Cyclosporine A and Sirolimus on genes and proteins involved in lipid metabolism in Wistar rats. Metab Clin Exp 63(5): 702-715., Lopes et al. 2014bLOPES PC, FUHRMANN A, CARVALHO F, SERENO J, SANTOS MR, PEREIRA MJ, ERIKSSON JW, REIS F & CARVALHO E. 2014b. Cyclosporine A enhances gluconeogenesis while sirolimus impairs insulin signaling in peripheral tissues after 3 weeks of treatment. Biochem Pharmacol 91(1): 61-73., Pereira et al. 2012PEREIRA MJ, PALMING J, RIZELL M, AURELIANO M, CARVALHO E, SVENSSON MK & ERIKSSON JW. 2012. MTOR inhibition with rapamycin causes impaired insulin signalling and glucose uptake in human subcutaneous and omental adipocytes. Mol Cell Endocrinol 355(1): 96-105., Pereira et al. 2013PEREIRA MJ, PALMING J, RIZELL M, AURELIANO M, CARVALHO E, SVENSSON MK & ERIKSSON JW. 2013. The immunosuppressive agents rapamycin, cyclosporin A and tacrolimus increase lipolysis, inhibit lipid storage and alter expression of genes involved in lipid metabolism in human adipose tissue. Mol Cell Endocrinol 365(2): 260-269., García-Casarrubios E et al. 2016 |
Antipsychotic drugs (ASDs) |
Olanzapine |
- Upregulates several genes involved in lipid biosynthesis in adipose tissues and decreases lipolytic activity on rat adipocyte - Induces low grade inflammatory state in adipose tissue of the rodent models - Reduces BAT thermogenesis in female rats |
Skrede et al. 2012SKREDE S ET AL. 2012. Olanzapine, but not aripiprazole, weight-independently elevates serum triglycerides and activates lipogenic gene expression in female rats. Int J Neuropsychopharmacol 15(2): 163-179., Albaugh et al. 2011ALBAUGH VL, JUDSON JG, SHE P, LANG CH, MARESCA KP, JOYAL JL & LYNCH CJ. 2011. Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis. Mol Psychiatr 16(5): 569-581., Victoriano et al. 2010VICTORIANO M, BEAUREPAIRE RD, NAOUR N, GUERRE-MILLO M, QUIGNARD-BOULANGÉ A, HUNEAU JF, MATHÉ V, TOMÉ D & HERMIR D. 2010. Olanzapine-induced accumulation of adipose tissue is associated with an inflammatory state. Brain Res 1350: 167-175., Li et al. 2019LI H, PENG S, LI S, LIU S, LV Y, YANG N & YU L. 2019. Chronic olanzapine administration causes metabolic syndrome through inflammatory cytokines in rodent models of insulin resistance. Nature 9: 1582., Zhang et al. 2014ZHANG Q, LIAN J, HE M, DENG C & WANG H. 2014. Olanzapine reduced brown adipose tissue thermogenesis and locomotor activity in female rats. Prog Neuro-Psychopharmacol Biological Psychiatry 51:172-180.
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Aripiprazole |
- Decreases triglyceride content of adipose tissue, increases multivacuolar cell presence, increase the pre-adipocytes proliferation in rats |
Skrede et al. 2012SKREDE S ET AL. 2012. Olanzapine, but not aripiprazole, weight-independently elevates serum triglycerides and activates lipogenic gene expression in female rats. Int J Neuropsychopharmacol 15(2): 163-179., Gall et al. 2013GALL Z, VANCEA S, MEZEI T & KOLCSAR M. 2013. Adipocyte Triglyceride Content and Adipogenesis in Aripiprazole Treated Rats. Int J Pharmacol 9(4): 251-257.
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Drugs used to treat cardiovascular risk factors |
Statins |
- Modulates thickness and inflammatory profile of human EAT (simvastatin and atorvastatin) |
Grosso et al. 2014GROSSO AF, OLIVEIRA SFD, HIGUCHI MDL, FAVARATO D, DALLAN LADO & LUZ PLD. 2014. Synergistic anti-inflammatory effect: Simvastatin and pioglitazone reduce inflammatory markers of plasma and epicardial adipose tissue of coronary patients with metabolic syndrome. Diabetol Metab Syndr 6(1): 1-8., Parisi et al. 2019PARISI V ET AL. 2019. Statin therapy modulates thickness and inflammatory profile of human epicardial adipose tissue. Int J Cardiol 274: 326-330.
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Antidiabetics |
Biguanides |
- No effect/Possible synergistic effect with DPP-4 inhibitors and/or GLP-1RAs on human EAT - Positive effects on VAT, inducing its reduction on diabetic subjects through a possible mechanism of fatty acid oxidation (metformin) |
Xourgia et al. 2018XOURGIA E, PAPAZAFIROPOULOU A & MELIDONIS A. 2018. Effects of antidiabetic drugs on epicardial fat. World J Diabetes 9(9): 141-148., Lima-Martínez et al. 2016LIMA-MARTÍNEZ MM, PAOLI M, RODNEY M, BALLADARES N, CONTRERAS M, D’MARCO L & IACOBELLIS G. 2016. Effect of sitagliptin on epicardial fat thickness in subjects with type 2 diabetes and obesity: a pilot study. Endocrine 51(3): 448-455., Iacobellis et al. 2017bIACOBELLIS G, MOHSENI M, BIANCO SD & BANGA PK. 2017b. Liraglutide causes large and rapid epicardial fat reduction. Obesity 25(2): 311-316., Tokubuchi et al. 2017TOKUBUCHI I, TAJIRI Y, IWATA S, HARA K, WADA N, HASHINAGA T, NAKAYAMA H, MIFUNE H & YAMADA K. 2017. Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats. PLoS One 12(2): e0171293.
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Thiazolidinediones |
- Decreases inflammatory cytokine release and thickness of human EAT (pioglitazone) - Induces a browning of the EAT of obese fatty Zucker rat that probably contributes to the increase in lipid turnover (rosiglitazone) |
Grosso et al. 2014GROSSO AF, OLIVEIRA SFD, HIGUCHI MDL, FAVARATO D, DALLAN LADO & LUZ PLD. 2014. Synergistic anti-inflammatory effect: Simvastatin and pioglitazone reduce inflammatory markers of plasma and epicardial adipose tissue of coronary patients with metabolic syndrome. Diabetol Metab Syndr 6(1): 1-8., Xourgia et al. 2018XOURGIA E, PAPAZAFIROPOULOU A & MELIDONIS A. 2018. Effects of antidiabetic drugs on epicardial fat. World J Diabetes 9(9): 141-148., Nagai et al. 2008NAGAI H ET AL. 2008. Pioglitazone Treatment Reduces Epicardial Fat in Patients with Type 2 Diabetes Mellitus and Improves Left Ventricular Diastolic Function. Circulation 118., Distel et al. 2012DISTEL E, PENOT G, CADOUDAL T, BALGUY I, DURANT S & BENELLI C. 2012. Early induction of a brown-like phenotype by rosiglitazone in the epicardial adipose tissue of fatty Zucker rats. Biochimie 94(8):1660-1667.
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GLP-1RAs |
- Reduces human EAT thickness (liraglutide and exenatide) |
Xourgia et al. 2018XOURGIA E, PAPAZAFIROPOULOU A & MELIDONIS A. 2018. Effects of antidiabetic drugs on epicardial fat. World J Diabetes 9(9): 141-148., Dutour et al 2016, Iacobellis et al. 2017bIACOBELLIS G, MOHSENI M, BIANCO SD & BANGA PK. 2017b. Liraglutide causes large and rapid epicardial fat reduction. Obesity 25(2): 311-316.
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DPP-4 inhibitors |
- Reduces human EAT thickness (sitagliptin) - UCP-1 up-regulation in BAT of the obese mice (sitagliptin) |
Xourgia et al. 2018XOURGIA E, PAPAZAFIROPOULOU A & MELIDONIS A. 2018. Effects of antidiabetic drugs on epicardial fat. World J Diabetes 9(9): 141-148., Lima-Martínez et al. 2016LIMA-MARTÍNEZ MM, PAOLI M, RODNEY M, BALLADARES N, CONTRERAS M, D’MARCO L & IACOBELLIS G. 2016. Effect of sitagliptin on epicardial fat thickness in subjects with type 2 diabetes and obesity: a pilot study. Endocrine 51(3): 448-455., Shimasaki et al. 2013SHIMASAKI T, MASAKI T, MITSUTOMI K, UENO D, GOTOH K, CHIBA S, KAKUMA T & YOSHIMATSU H. 2013. The Dipeptidyl Peptidase-4 Inhibitor Des-Fluoro-Sitagliptin Regulates Brown Adipose Tissue Uncoupling Protein Levels in Mice with Diet-Induced Obesity. PLoS One 8(5): 1-11.
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SGLT2 inhibitors |
- Increases glucose uptake, reduced proinflammatory chemokines secretion and Improves differentiation of human EAT cells (dapagliflozin) |
Xourgia et al. 2018XOURGIA E, PAPAZAFIROPOULOU A & MELIDONIS A. 2018. Effects of antidiabetic drugs on epicardial fat. World J Diabetes 9(9): 141-148., Díaz-Rodríguez et al. 2018DÍAZ-RODRÍGUEZ E, AGRA RM, FERNÁNDEZ ÁL, ADRIO B, GARCÍA-CABALLERO T, GONZÁLEZ-JUANATEY JR & EIRAS S. 2018. Effects of dapagliflozin on human epicardial adipose tissue: Modulation of insulin resistance, inflammatory chemokine production, and differentiation ability. Cardiovasc Res 114(2): 336-346., Sato et al. 2018SATO T ET AL. 2018. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol 17(6): 1-9.
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