The effect of carbamazepine treatment on serum leptin levels

Uludağ, İrem Fatma; Kulu, Ugur; Şener, Ufuk; Köse, Şükran; Zorlu, Yaşar

doi:10.1016/j.eplepsyres.2009.04.005

Cited by 15 publications

(8 citation statements)

References 41 publications

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“…Recent studies have revealed that treatment with carbamazepine increases the levels of total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations in serum without significantly affecting circulating insulin or leptin levels, suggesting the effect of carbamazepine in cholesterol metabolism [7,10,11]. Adipose tissue forms the major cholesterol pool of the human body [12].…”

Section: Introductionmentioning

confidence: 99%

Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression

Kim

Chau

et al. 2019

Cells

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Carbamazepine is a drug that is widely used in the treatment of epilepsy and bipolar disorder. The prevalence of obesity in patients treated with carbamazepine has been frequently reported. However, whether carbamazepine affects adipogenesis, one of the critical steps in the development of obesity, remains unclear. Here, we show that carbamazepine increased the expression levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein β (C/EBPβ), and fatty acid synthase (FASN) in 3T3-L1 cells. Notably, carbamazepine inhibited the expression levels of β-catenin, a negative regulator of adipogenesis, leading to enhanced adipogenesis. Conversely, β-catenin overexpression abolished the effect of carbamazepine on adipogenic gene expression. However, depletion of β-catenin further enhanced PPARγ expression. In addition, carbamazepine reduced β-catenin expression by lowering the levels of phospho-low density lipoprotein receptor-related protein 6 (p-LRP6) and phospho-glycogen synthase kinase 3β (p-GSK3β) in Wnt/β-catenin signaling. Moreover, carbamazepine reduced Wnt mRNA expression and decreased the promoter activities of TCF, the target of β-catenin during adipogenesis. These results suggest that carbamazepine enhances adipogenesis by suppressing Wnt/β-catenin expression, indicating its potential effects on obesity-related metabolism.

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Section: Introductionmentioning

confidence: 99%

Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression

Kim

Chau

et al. 2019

Cells

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“…CBZ, a dibenzazepine, has been used as a treatment for epilepsy and bipolar mood disorders for decades. It has been suggested to induce a moderate weight gain in patients (Joffe et al, 1986;Lampl et al, 1991), but these observations remain controversial (Caksen et al, 2003;Uludag et al, 2009). However, very few data are available on the exact metabolic effect of CBZ: it has been reported to increase high-density lipoprotein-and low-density lipoprotein-cholesterol plasma levels (Hamed et al, 2009;Luef et al, 2009), while it does not modify insulin and leptin circulating levels (Hamed et al, 2009;Luef et al, 2009;Uludag et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Carbamazepine directly inhibits adipocyte differentiation through activation of the ERK 1/2 pathway

Turpin

Muscat

Vatier

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSECarbamazepine (CBZ), known for its anti-epileptic, analgesic and mood-stabilizing properties, is also known to induce weight gain but the pathophysiology of this adverse effect is still largely unknown. We tested the hypothesis that CBZ could have a direct effect on adipocyte development and metabolism. EXPERIMENTAL RESEARCHWe studied the effects of CBZ on morphological biochemical and molecular markers of adipogenesis, using several pre-adipocyte murine cell lines (3T3-L1, 3T3-F442A and T37i cells) and primary cultures of human pre-adipocytes. To delineate the mechanisms underlying the effect of CBZ, clonal expansion of pre-adipocytes, pro-adipogenic transcription factors, glucose uptake and lipolysis were also examined. KEY RESULTSCBZ strongly inhibited pre-adipocyte differentiation and triglyceride accumulation in a time-and dose-dependent manner in all models. Pleiotropic mechanisms were at the basis of the inhibitory effects of CBZ on adipogenesis and cell lipid accumulation. They included suppression of both clonal expansion and major adipogenic transcription factors such as PPAR-g and CCAAT/enhancer binding protein-a, activation of basal lipolysis and decrease in insulin-stimulated glucose transport. CONCLUSIONS AND IMPLICATIONSThe effect of CBZ on adipogenesis involves activation of the ERK1/2 pathway. Our results show that CBZ acts directly on pre-adipocytes and adipocytes to alter adipose tissue development and metabolism. AbbreviationsACC, acetyl-CoA carboxylase; C/EBP-a, CCAAT/enhancer binding protein-a; C/EBP-b, CCAAT/enhancer binding protein-b; CBZ, carbamazepine; DOG, deoxyglucose; FAS, fatty acid synthase; G3PDH, glycerol-3-phosphate dehydrogenase; HSL, hormone-sensitive lipase; MEK, MAPK/ERK kinase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; SREBP-1c, sterol regulatory element-binding protein 1c

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“…Previous studies 5 15 25 have reported increase in BMI in VPA treated subjects in a range of 2 to 4 kg/m 2 , however, de Vries et al 26 have reported no increase in BMI after VPA treatment. There are previous studies demonstrating neutral effect of CBZ 4 10 19 , PHT 5 15 and LTG 4 19 . However, some studies reported that women on CBZ and LTG had a greater BMI when compared with the control group 15 27 .…”

Section: Discussionmentioning

confidence: 93%

“…Some studies have reported unfavourable effects of VPA on lipid profile like reduction in high density lipoprotein (HDL)-cholesterol and increase in triglyceride (TG) levels 4 9 . Reports on the effects of CBZ and PHT on lipid profile are contradictory 4 10 11 , and a few studies have demonstrated neutral effect of LEV and LTG on lipid profile 11 . Thus, the effect of chronic AEDs treatment on the lipid profile is inconclusively reported.…”

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confidence: 99%

Comparison of body composition in persons with epilepsy on conventional & new antiepileptic drugs

et al. 2016

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Background & objectives:Certain antiepileptic drugs (AEDs) such as valproic acid (VPA) are known to affect body weight, and lipid profile. However, evidences regarding effects of AEDs on the body composition are deficient. This cross-sectional study compared the body composition and lipid profile among patients with epilepsy on newer and conventional AEDs.Methods:The patients with epilepsy (n=109) on treatment with conventional and newer AEDs (levetiracetam, lamotrigine and clobazam) for > 6 months were enrolled. Of these, 70 were on monotherapy: levetiracetam (n=12), VPA (n=16), carbamazepine (n=20) and phenytoin (n=22) and the remaining on polytherapy. Their body composition [body fat mass, lean dry mass (LDM), total body water (TBW), intracellular water (ICW), extracellular water (ECW) and basal metabolic rate (BMR) was estimated and biochemical parameters were assessed.Results:Levetiracetam group had no significant difference with VPA, carbamazepine, phenytoin and control groups, except low LDM (17.8±2.4) than VPA groups (20.2±2.7, P<0.05). In comparison with control, AEDs monotherapy groups had no significant difference, except higher LDM and ECW in VPA group. Among groups based on conventional and newer AEDs, there was no significant difference in body composition parameters except for higher LDM (as % of BW) in conventional AEDs only treated group than control (P<0.01).Interpretation & conclusions:The alterations observed in body composition with valproic acid in contrast to other AEDs like levetiracetam, carbamazepine and phenytoin could affect treatment response in epilepsy especially in subjects with already altered body composition status like obese and thin frail patients, which needs to be established by prospective studies (CTRI/2013/05/003701).

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The effect of carbamazepine treatment on serum leptin levels

Cited by 15 publications

References 41 publications

Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression

Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression

Carbamazepine directly inhibits adipocyte differentiation through activation of the ERK 1/2 pathway

Comparison of body composition in persons with epilepsy on conventional & new antiepileptic drugs

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