Attention deficit hyperactivity disorder in children with epilepsy: a multicenter cross-sectional analysis in China.

BACKGROUND: The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life. METHODS: We carried out a multicenter cross-sectional survey of children with epilepsy across China between March 2022 and August 2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD. RESULTS: Overall, 395 epilepsy patients aged 6-18 years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15 years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD. CONCLUSIONS: While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy.

The image quality, lesion detectability, and acquisition time of 18F-FDG total-body PET/CT in oncological patients.

PURPOSE: The purpose was to investigate the effects of short acquisition time on the image quality and the lesion detectability of oncological 18F-FDG total-body PET/CT. METHODS: Nineteen oncological patients (6/13 women/men, age 65.6 ± 9.4 years) underwent total-body PET/CT on uEXPLORER scanner using 3D list mode. The administration of 18F-FDG was weight-based (4.4 MBq/kg). The acquisition time was 900 s, and PET data were reconstructed into 900-, 180-, 120-, 60-, 30-, and 18-s duration groups. The subjective PET image quality was scored using a 5-point scale (5, excellent; 1, poor) in 3 perspectives: overall quality, noise, and lesion conspicuity. The objective image quality was evaluated by SUVmax and standard deviation (SD) of the liver, SUVmax of the tumor, and tumor-to-background ratio (TBR). The lesion detectability was the percentage of identifiable lesions in the groups of 180 to 18 s using the group 900 s as reference. RESULTS: Our results showed that sufficient and acceptable subjective image quality could be achieved with 60- and 30-s groups, and good image quality scores were given to 180- and 120-s groups without significant difference. For shortened acquisition time, SD was increased, while SUVmax of tumor and TBR remained unchanged. The lesion detectability was decreased with shorter acquisition time, but the detection performance could be maintained until the 60-s group compared with the 900-s group, although the image quality degraded. CONCLUSION: The total-body PET/CT can significantly shorten the acquisition time with maintained lesion detectability and image quality.

Acute disseminated encephalomyelitis following varicella-zoster virus infection: Case report of effective treated both in clinical symptom and neuroimaging.

INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is an idiopathic inflammatory demyelinating disorder of the central nervous system (CNS). Early treatment is the key for neurological recovery. METHODS: A case of ADEM associated with varicella-zoster virus infection was presented, in which magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) examinations were included. RESULTS: Magnetic resonance imaging of the brain revealed multiple hyperintense lesions at the subcortical level on fluid-attenuated inversion recovery (FLAIR), and MRI of the spinal cord revealed longitudinally segmented hyperintense lesions at the spinal cord on T2-weighted images. The patient was treated with methylprednisolone and gancyclovir, and had a favorable recovery. Subsequent MRI of the brain and cervical cord showed the previous abnormal hyperintensities had markedly disappeared. CONCLUSION: A rare case of ADEM with longitudinal segmented hyperintense lesions at the spinal cord on T2-weighted images was presented. Excellent response to ADEM treatment with high-dose steroids was reported resulting in a remarkable neurological recovery. A long-term follow-up is needed for prognosis.

Autoimmune encephalitis mimicking sporadic Creutzfeldt-Jakob disease: A retrospective study.

Autoimmune encephalitis associated with anti-voltage-gated potassium channel antibodies are most likely to be misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Our goal was to delineate patients who were initially suspected to have CJD but were later found to have AE. We performed a retrospective clinical review of cases of individuals and made a comparison between groups of patients diagnosed with sCJD and AE. Patients who had rapidly progressing dementia and focal neurological impairment, such as aphasia, gait disturbance, visual disturbance, and depression, at onset were diagnosed with sCJD, whereas epilepsy, hyponatremia and dysautonomia were strong hints for AE. Fluoroscope-positron emission tomography (PET) of patients with AE revealed variable metabolism and normative and long-term immunosuppression were less likely to relapse.

Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China.

BACKGROUND: It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy. METHODS: This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated. RESULTS: A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%). CONCLUSION: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure, 12-month remission rate, and retention rate.

Lamotrigine induced DIHS/DRESS: Manifestations, treatment, and outcome in 57 patients.

OBJECTIVE: To evaluate the clinical features, course, response to treatment, and outcome of lamotrigine induced drug-induced hypersensitivity syndrome (DIHS) or drug reaction with eosinophilia and systemic symptoms (DRESS). METHODS: A comprehensive PubMed and Scopus search (covering the period from January 1999 through April 2014) of the English and non-English literature (with English abstract) was conducted to identify published reports of severe cutaneous adverse reactions (SCARs) associated with lamotrigine therapy. RESULTS: This study population included 57 patients, of whom 38 (66.67%) were female and 19 (33.33%) were male. The latency period varied from 9 days to 120 days, with a mean of 27.58 ± 20.65 days. Multisystem involvement was present in 97.37% (37/38) patients. Systemic corticosteroids were administered to (61.29%) 19/31 patients. 35/38 (92.11%) patients recovered completely, one patient developed liver failure and needed liver transplant, one died from septic shock and one died from multiple organ failure. CONCLUSIONS: We found a greater predominance of women with LTG-DIHS/DRESS, and 68.42% patients were >18 years of age. The presenting symptoms in most of patients were fever, skin rash, liver involvement, hypereosinophilia, and lymphadenopathy. Lamotrigine is associated to a rather high risk of severe cutaneous adverse reactions and to the risk of dying from such reactions, likes many other anticonvulsants. Early recognition and withdrawal of the suspected agent may avoid irreversible damage to the organs will be life saving.

Evaluation of clinical features of elderly epilepsy in China.

Recent data indicate that the prevalence and incidence of epilepsy are high among the elderly, many of whom will have concomitant neurodegenerative, cerebrovascular, or neoplastic disease. The aim of this study is to evaluate the clinical characteristics of elderly patients with epilepsy in China. We retrospectively reviewed the clinical records of 104 outpatients over 50 years of age (average: 63.8 years). The results showed that in the total 104 outpatients, 53 men and 51 women were studied. Twenty-seven (26.0%) patients had idiopathic epilepsy syndromes, and 15 (14.4%) patients were considered cryptogenic. Sixty-two (59.6%) patients had remote symptomatic epilepsy. According to the known etiological factors, cerebrovascular disease (53.2%) is the most common underlying cause, followed by craniocerebral trauma (16.1%), primary or metastatic neoplastic disease (16.1%), and others (14.5%). The most common type of seizure in the group studied was partial seizures (51.9%), followed by generalized seizures (37.5%). Forty-three patients (41.3%) were used combination medication and 61 patients (58.7%) were used single medication. In conclusions, this study provides important data for clinical and research purposes in China. Further research is indicated to confirm the clinical findings of the elderly people with epilepsy by a larger epidemiological study.

Lamotrigine-induced severe cutaneous adverse reaction: Update data from 1999-2014.

We systematically reviewed and analyzed published patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) associated with lamotrigine therapy to identify characteristics of these reactions. We identified a total of 70 patients (42 SJS, five SJS/TEN, 23 TEN). The female to male ratio was 2.83:1 in the TEN group and 1.47:1 in the SJS group. Patients in the TEN group were younger than in the SJS group but this difference was not significant (28.35 versus 32.71 years, respectively; p=0.27). The median time to onset was 25.33 versus 18.42 days for SJS and TEN, respectively. The median dosage at onset was 36.46 versus 57.29mg, and final dosage 111.25 versus 97.92mg/day for SJS and TEN, respectively. The median final dosages did not significantly differ. Concomitant use of valproate acid was reported in 54.55% of the SJS patients and 50.00% of the TEN patients. Three fatal reactions were reported, of which two patients deteriorated rapidly and died within 12h of admission, indicating that this disease can develop rapidly before effective treatment. There was no significant difference between the SJS and TEN groups in any of the clinical factors examined which confirmed the opinion that SJS and TEN are part of a single disease spectrum.

Hydroxysafflor yellow A (HYSA) inhibited the proliferation and differentiation of 3T3-L1 preadipocytes.

Hydroxysafflor yellow A (HSYA), a main component of safflor yellow, has been demonstrated to prevent steroid-induced avascular necrosis of femoral head by inhibiting primary bone marrow-derived mesenchymal stromal cells adipogenic differentiation induced by steroid. In this study, we investigate the effect of HSYA on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes. The effects of HSYA on proliferation and differentiation of 3T3-L1 cells and its possible mechanism were studied by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide spectrophotometry, Oil Red O staining, intracellular triglyceride assays, real-time quantitative RT-PCR, transient transfection and dual luciferase reporter gene methods. HSYA inhibited the proliferation of 3T3-L1 preadipocytes and cell viability greatly decreased in a dose and time dependent manner. HSYA (1 mg/l) notably reduced the amount of intracellular lipid and triglyceride content in adipocytes by 21.3 % (2.13 ± 0.36 vs 2.71 ± 0.40, P < 0.01) and 22.6 % (1.33 ± 0.07 vs 1.72 ± 0.07, P < 0.01) on days 8 following the differentiation, respectively. HSYA (1 mg/l) significantly increased hormone-sensitive lipase (HSL) mRNA expression and promoter activities by 2.4- and 1.55-fold, respectively (P < 0.01), in differentiated 3T3-L1 adipocytes. HSYA inhibits the proliferation and adipogenesis of 3T3-L1 preadipocytes. The inhibitory action of HYSA on adipogenesis may be due to the promotion of lipolytic-specific enzyme HSL expression by increasing HSL promoter activity.

Risk of a lamotrigine-related skin rash: current meta-analysis and postmarketing cohort analysis.

PURPOSE: We systematically reviewed studies to provide current evidence on the incidence and risk of skin rash in patients with LTG therapy. METHODS: PubMed and Scopus databases, up to 15 March 2014 were searched to identify relevant studies. Eligible studies included prospective studies, retrospective studies and postmarketing reports, which included data of skin rash in patients with LTG therapy. RESULTS: Forty-one articles met the entry criteria. A total of 4447 patients with LTG therapy from 26 prospective studies, 2977 patients from 8 retrospective studies, and 26,126 patients from 5/7 postmarketing reports were included. The overall incidence of skin rash with LTG therapy was 9.98% (444/4447) from prospective studies, 7.19% (214/2977) from retrospective studies, and 2.09% (547/26,126) from postmarketing reports. A meta-analysis of the risk of skin rash in 21 prospective studies, did not show a significant difference between patients with LTG and other drugs, including placebo, other ADEs or lithium (OR 0.99-2.41). In 6 respective studies, there was a significantly higher OR in patients with LTG compared with those with non-aromatic AEDs. However, there was no significant difference in rash risk between patients with LTG and aromatic AEDs. CONCLUSIONS: Our study showed that LTG significantly increased the risk of developing a skin rash compared to non-aromatic AEDs. Our results support the need for large prospective population-based studies and clinical trials to determine whether LTG increases the risk of developing a skin rash than compared to other drugs.

Changes and overlapping distribution in the expression of CB1/OX1-GPCRs in rat hippocampus by kainic acid-induced status epilepticus.

Status epilepticus (SE) is a life-threatening neurological disorder. It is important to discover new drugs to control SE without the development of pharmacoresistance. Focus on the cannabinoid receptor and cannabinoid-related compounds might be a good option. Cannabinoid receptor 1 (CB1) and orexin receptor 1 (OX1) both belong to the GPCR superfamily and display "cross-talk" interactions, however, there has been no study of the effect of OX1/CB1 in epilepsy. Therefore, we investigated the potential long-term effects of SE on CB1 and OX1 expression in rat hippocampus, aiming to elucidate whether they are involved in the causative mechanism of epilepsy and whether they might form a heterodimer. In this study, SE was induced with kainic acid, and results of immunohistochemistry and RT-PCR both showed that the expression of CB1 in the hippocampus increased after SE and was significantly higher compared to controls especially 1 week post-SE. However we did not find any significant difference in the expression of OX1 between the SE group and the controls at any time. Under immunofluorescence staining, we observed an overlapping distribution of CB1 and OX1 in the hippocampus. The increased expression of CB1 in the hippocampus indicates that CB1 may play an important role in the underlying mechanism of SE, but the effect of OX1 was not obvious. The overlapping distribution of CB1 and OX1 in the hippocampus indicates that they may form a heterodimer to exert their effect in epilepsy.

High prevalence of headaches in patients with epilepsy.

BACKGROUND: To examine the association between headaches and epilepsy. METHODS: Consecutive adult epileptic patients who went to the outpatient clinic of the Epilepsy Center of PLA General Hospital between February 01, 2012, and May 10, 2013, were recruited into this study. A total of 1109 patients with epilepsy completed a questionnaire regarding headaches. RESULTS: Overall, 60.1% of the patients (male: 57.2%; female: 63.8%) reported headaches within the last year. The age-weighted prevalence of interictal migraine was 11.7% (male 8.9%, female 15.3%), which is higher than that reported in a large population-based study (8.5%, male 5.4%, female 11.6%) using the same screening questions. The prevalence of postictal headaches was 34.1% (males 32.7%, females 35.2%), and the presence of preictal headaches was 4.5% (males 4.3%, females 5.2%). The prevalence of headache yesterday in the general population was 4.8% (male 3.0%, female 6.6%). Thus, the prevalence of headaches, including migraine, is higher in epileptic patients in China. CONCLUSIONS: The high prevalence of postictal headaches confirms the frequent triggering of a headache by a seizure. A much lower frequency of preictal headaches, a condition in which the real triggering effect of the headache on the seizure might be difficult to prove.

The changes of serum glypican4 in obese patients with different glucose metabolism status.

CONTEXT AND OBJECTIVE: Glypican 4 (Gpc4) was identified as a novel adipokine capable of intensifying insulin signaling and regulating adipocyte differentiation. This study was performed to investigate the changes of serum Gpc4 levels in obese patients with different glucose metabolism status and its association with metabolic-related parameters. DESIGN AND PARTICIPANTS: A total of 170 obese patients with different glucose metabolism status and 38 normal controls were recruited, and obese patients were divided into 4 groups: OB1, obese patients with normal glucose tolerance (NGT) and normal insulin levels; OB2, obese patients with normal glucose tolerance and hyperinsulinemia; OB3, obese patients with impaired glucose tolerance; and OB4, obese patients with type 2 diabetes mellitus. Serum Gpc4 was determined by commercially available ELISA kits. RESULTS: Serum Gpc4 levels in the OB2, -3, and -4 groups were significantly increased in comparison with that in the OB1 group (3.5 [2.0-5.3] ng/mL, 3.0 [1.5-6.1] ng/mL, and 3.4 [1.8-5.4] ng/mL vs 1.9 [1.3-4.3] ng/mL, P < .05). The levels were positively correlated with body mass index (BMI), systolic blood pressure (SBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) in all subjects. Multiple linear regression showed that SBP, AST, HOMA-IR, and FINS were independent contributors to circulating Gpc4 levels after adjusting for age, gender, and BMI in all subjects (P < .05). Additionally, serum Gpc4 levels in males of the normal group and the OB3 group were higher than those in females (2.9 [2.1-4.9] ng/mL vs 1.6 [1.2-3.1] ng/mL; 4.8 [2.5-6.3] ng/mL vs 2.7 [1.1-4.4] ng/mL, P < .05). CONCLUSIONS: Serum Gpc4 levels were significantly elevated in obese patients with insulin resistance and positively correlated with BMI, SBP, ALT, AST, FINS, and HOMA-IR, suggesting Gpc4 is a novel adipokine associated with obesity and insulin resistance-related metabolic disorders.

Serum Levels of the Adipokine Zinc- α 2-glycoprotein Are Decreased in Patients with Hypertension.

Objective. Zinc-α2-glycoprotein (ZAG) has recently been proposed as a new adipokine involved in body weight regulation. The purpose of this study is to investigate serum levels of ZAG in patients with hypertension and its association with related characteristics. Methods. 32 hypertension patients and 42 normal controls were recruited and the relationship between serum ZAG, total and high molecular weight (HMW) adiponectin, and tumor necrosis factor-α (TNFα) determined by enzyme-linked immunosorbent assay (ELISA) and metabolic-related parameters was investigated. Results. Serum ZAG concentrations were significantly lowered in patients with hypertension compared with healthy controls (61.4 ± 32 versus 78.3 ± 42 µg/mL, P < 0.05). The further statistical analysis demonstrated that serum ZAG levels were negatively correlated with waist-to-hip ratio (WHR) (r = -0.241, P < 0.05) and alanine aminotransferase (ALT) (r = -0.243, P < 0.05). Additionally, serum HMW adiponectin significantly decreased, while TNFα greatly increased in hypertension patients as compared with healthy controls (2.32 ± 0.41 versus 5.24 ± 1.02 µg/mL, 3.30 ± 1.56 versus 2.34 ± 0.99 pg/mL, P < 0.05). Conclusions. Serum ZAG levels are significantly lowered in hypertension patients and negatively correlated with obesity-related item WHR, suggesting ZAG is a factor associated with hypertension.

Hormone-sensitive lipase is involved in the action of hydroxysafflor yellow A (HYSA) inhibiting adipogenesis of 3T3-L1cells.

BACKGROUND: Safflor yellow A (SY) has been demonstrated to be beneficial to cardiovascular system. Our previous study showed that hydroxysafflor yellow A (HSYA), a main component of SY, could increase peroxisome proliferator-activated receptor γ mRNA expression. In this study, we investigate the effect of HSYA on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes. METHODS: The proliferation and adipogenesis of 3T3-L1 cells treated with HSYA was studied by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) spectrophotometry, Oil Red O staining and intracellular triglyceride assay methods. HSL mRNA expression and promoter activity were studied by real-time quantitative RT-PCR, transient transfection and dual luciferase reporter gene methods. RESULTS: HSYA (0.1 mg/L) significantly inhibited the proliferation of 3T3-L1 cells when compared with control cells in 8 h. This effect was further enhanced with the extension time (24 to 96 h) and an increase of concentration of HSYA (1-10 mg/L). The maximal inhibitory action was observed at 0.1 mg/L HSYA in 72 h (86±11.8% vs. 100±4.1%, p<0.01). HSYA notably reduced the amount of intracellular lipid and triglyceride content in adipocytes to 85% (1 mg/L) and 75% (100 mg/L) on Day 4 following the differentiation, respectively, while increased HSL mRNA expression and promoter activities to 2.7 fold and 1.55 fold, respectively (p<0.01), in differentiated 3T3-L1 adipocytes. CONCLUSIONS: HSYA inhibits the proliferation and adipogenesis of 3T3-L1 preadipocytes. The inhibitory action of HYSA on adipogenesis may be due to the promotion of lipolytic-specific enzyme HSL expression by increasing HSL promoter activity.

Comorbidity between headache and epilepsy in a Chinese epileptic center.

Here we investigated the characteristics and prevalence of headaches in patients with epilepsy in a Chinese epileptic center based on the International Classification of Headache Disorders, 2nd edition. We found that 60.14% (667/1109) of patients reported headaches. Headache was less prevalent in males (57.17%) than in females (63.75%). Interictal headaches were present in 34.62% of patients, and 139/1109 (12.53%) patients had interictal migraine, which was a higher percentage than reported in a large population-based study from the same area (9.3%) using the same screening question. In addition, 469 (70.31%) patients had postictal headache, migraine characteristics were present in 73.35% of these patients, and 15.35% also suffered from interictal migraine. Lastly, 8.85% patients had preictal headache. These results confirm that headache is very common in patients with epilepsy. Seizures often trigger postictal headaches with migraine features. The comorbidity of migraines and epilepsy should receive clinical attention, as it may influence antiepileptic drug choice, and the headache may require specific treatment.

Clinical factors associated with postictal headache in Chinese patients with partial epilepsy.

PURPOSE: To investigate the incidence of postictal headache (PIH) and the factors potentially related to the occurrence of PIH in a Chinese epileptic center. METHODS: Consecutive adult patients with epilepsy, referred to the outpatient clinic of the Epilepsy Center of the PLA General Hospital between February 01, 2012, and May 10, 2013, were recruited to this study. 854 patients with partial epilepsy completed a questionnaire regarding headache, 466 patients with temporal lobe epilepsy (TLE), 82 patients with occipital lobe epilepsy (OLE) and 306 patients with frontal lobe epilepsy (FLE). A semi-structured interview was performed in those who confirmed headache. RESULTS: PIH occurred in 328 (38.41%) of the subjects. By type of epilepsy, PIH was found in 164 (35.19%) of the patients with TLE, 46 (56.01%) of the patients with OLE, and 118 (38.56%) of the patients with FLE. The incidence of PIH in OLE was significantly higher than in TLE and FLE (P<0.05). It occurs more frequently after generalized tonic-clonic seizures than other seizure types. Logistic regression analysis revealed that age at onset, type of seizure and classification of epilepsy were each significantly related to the occurrence of PIH. CONCLUSION: The results of our study revealed possible relationships between PIH and the region of epileptic focus and area of spread of epileptic discharges.

Inhibition of preadipocyte differentiation and adipogenesis by zinc-α2-glycoprotein treatment in 3T3-L1 cells.

AIMS/INTRODUCTION: Zinc-α2-glycoprotein (ZAG) is associated with the loss of adipose tissue in cancer cachexia, and has recently been proposed to be a candidate factor in the regulation of bodyweight. The aim of the study was to investigate the effects of ZAG on the proliferation and differentiation of 3T3-L1 preadipocytes. MATERIALS AND METHODS: 3-(4,5-Dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) spectrophotometry, Oil Red O staining, intracellular triglyceride assays, real-time quantitative reverse transcription polymerase chain reaction and transient transfection methods were used to explore the action of ZAG. RESULTS: Ectopic ZAG expression significantly stimulates 3T3-L1 cells proliferation in a dose- and time-dependent manner. The maximum influence of ZAG on proliferation was 1.43-fold higher than what was observed in control cells. This effect was observed 144 h after transfection with 0.16 µg of murine ZAG (mZAG) plasmid (P < 0.001). The intracellular lipids content in mZAG over-expressing cells were decreased as much as 37% when compared with the control cells after differentiation (P < 0.05, P < 0.01). The messenger ribonucleic acid levels of peroxisome proliferators-activated receptor-γ (PPARγ), CCAAT enhancer-binding protein-α (C/EBPα) and the critical lipogenic gene, fatty acid synthase (FAS), are also downregulated by up to 50% in fully differentiated ZAG-treated adipocytes. ZAG suppresses FAS messenger ribonucleic acid expression by reducing FAS promoter activity. CONCLUSIONS: Zinc-α2-glycoprotein stimulates the proliferation and inhibits the differentiation of 3T3-L1 murine preadipocytes. The inhibitory action of ZAG on cell differentiation might be a result of the attenuation of the expression of PPARγ, C/EBPα and the lipogenic-specific enzyme FAS by reducing FAS promoter activity.