CREBH Regulates Systemic Glucose and Lipid Metabolism

The cyclic adenosine monophosphate (cAMP)-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins related to lipoprotein lipase (LPL) activation. CREBH in the small intestine reduces cholesterol transporter gene Npc1l1 and suppresses cholesterol absorption from diet. A deficiency of CREBH in mice leads to severe hypertriglyceridemia, fatty liver, and atherosclerosis. CREBH, in synergy with peroxisome proliferator-activated receptor α (PPARα), has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis including glucose and lipid metabolism. CREBH binds to and functions as a co-activator for both PPARα and liver X receptor alpha (LXRα) in regulating gene expression of lipid metabolism. Therefore, CREBH has a crucial role in glucose and lipid metabolism in the liver and small intestine

Effect of anti-attention-deficit hyperactivity disorder (ADHD) medication on clinical seizures and sleep EEG : A retrospective study of Japanese children with ADHD

Publisher Copyright: © 2021 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.Aims: Patients with attention-deficit hyperactivity disorder (ADHD) often exhibit basic or paroxysmal wave abnormalities on electroencephalography (EEG). Methylphenidate (MPH), an anti-ADHD stimulant, has been reported to lower the seizure threshold. However, there have been no reports comparing EEG changes before and after administration of the central nervous system (CNS) stimulant MPH, or atomoxetine (ATX) hydrochloride, a non-CNS stimulant. In this study, we investigated changes in sleep EEG before and after the administration of ADHD treatment drugs. Method: With the approval of the ethics committee, the medical records of 28 children with ADHD (23 men and 5 women) who gave consent were retrospectively investigated. The appearance of sudden abnormal waves during a 10-minute sleep EEG recording was measured in 0.1-second units, and the duration of these waves was calculated as the paroxysmal index (PI). Results: Paroxysmal index did not differ significantly between patients who received MPH and those who received ATX. In addition, there were no exacerbations of clinical seizures. Conclusion: It was concluded that ADHD medications do not have an adverse effect on epileptic seizures or abnormal sleep EEGs.Peer reviewe

Clinical profile of reading ability and reading and writing achievement of children with borderline full-scale intellectual quotient : a prospective study

Background Poor reading ability is one of the common causes of low academic performance. In previous studies, children with dyslexia were found to demonstrate poor academic achievement due to poor reading ability. However, the relationship between academic achievement and reading ability in children with a borderline full-scale intellectual quotient (FSIQ) is unknown. This study aimed to clarify the clinical characteristics of children with borderline FSIQ and poor reading ability, and differentiate these characteristics from those of children with higher FSIQ and poor reading ability. Methods A total of 126 children (aged 6-15 years) identified as having low academic performance were enrolled. The reading ability of children was assessed through their performance on the hiragana (Japanese syllabary) reading task, while their reading and writing achievement was assessed through their reading and writing score on the Kaufman Assessment Battery for Children, Second Edition. Children were categorized into two groups based on their FSIQ score (FSIQ > 85 and 85 >= FSIQ >= 70). Reading ability in children was evaluated by referring to the linear relationship between FSIQ and the standard deviation value of reading tasks in typically developing children. A one-way analysis of variance (ANOVA) was performed to examine clinical characteristics between higher and lower FSIQ groups. Associations between reading and writing achievement, reading ability, and ages of children were assessed using Pearson's product-moment correlation coefficients for the higher and lower FSIQ groups. Results Poorer reading and writing achievement was associated with poorer reading ability in the higher FSIQ group. Conversely, poorer reading and writing achievement and poor reading ability were associated with older age in the lower FSIQ group. Conclusions Poor reading and writing achievement were associated with older age, not with poor reading ability in the lower FSIQ group. Children with lower FSIQ need appropriate educational interventions based on independent assessments to further their academic achievement and reading ability. Moreover, they need more frequent evaluations of their academic achievement than do children with higher FSIQ and poor reading ability since they are more likely to be at a lower academic achievement level at an older age.Peer reviewe

Transgenic mice overexpressing SREBP-1a under the control of the PEPCK promoter exhibit insulin resistance, but not diabetes

AbstractSterol regulatory element-binding protein-1 (SREBP-1) is a transcription factor which regulates genes involved in the synthesis of fatty acids and triglycerides. The overexpression of nuclear SREBP-1a in transgenic mice under the control of the PEPCK promoter (TgSREBP-1a) caused a massively enlarged fatty liver and disappearance of peripheral white adipose tissue. In the current study, we estimated the impact of this lipid transcription factor on plasma glucose/insulin metabolism in vivo. TgSREBP-1a exhibited mild peripheral insulin resistance as evidenced by hyperinsulinemia both at fasting and after intravenous glucose loading, and retarded glucose reduction after insulin injection due to decreased plasma leptin levels. Intriguingly, hyperinsulinemia in TgSREBP-1a mice was markedly exacerbated in a fed state and sustained after intravenous glucose loading, and paradoxically decreased after the portal injection of glucose. TgSREBP-1a mice consistently showed very small plasma glucose increases after portal glucose loading because of a large capacity for hepatic glucose uptake. These data suggested that hepatic insulin resistance emerges postprandially. In addition, pancreatic islets from TgSREBP-1a were enlarged. These data demonstrate that SREBP-1a activation in the liver has a strong impact on plasma insulin levels, implicating the potential role of SREBPs in hepatic insulin metabolism relating to insulin resistance

Design, Construction and Test of a Small Bitter Magnet usable for a Hybrid Magnet

A hybrid magnet is a combined system of an outer superconducting magnet and an inner high-power water-cooled magnet, generating continuous high magnetic fields. A small Bitter coil to be used for the latter magnet has been designed, constructed and tested up to the DC electric power of 3 MW and the deionized-water flow rate of 130 m^3/h. According to expectations, the field produced in a clear bore of 32 mm diameter has reached 12.4 T without an excessive temperature rise of the coil

Design, Construction and Test of a Double Bitter Magnet

A Bitter magnet with concentric double coils is more efficient than a single-coil magnet especially at a high level of power consumption. The newly constructed double Bitter magnet has been tested up to the power of 3 MW. Some results of mechanical tests for conductor and insulator materials are also described

Mitochondrial intermediate peptidase is a novel regulator of sirtuin-3 activation by caloric restriction

Sirtuin-3 (SIRT3) regulates mitochondrial quality and is involved in the anti-ageing and pro-longevity actions of caloric restriction (CR). Here, we show that CR upregulates the mature form of SIRT3 and mitochondrial intermediate peptidase (MIPEP), a mitochondrial signal peptidase (MtSPase), in white adipose tissue. We also demonstrate that upregulation of mature SIRT3 is dependent on MIPEP in 3T3-L1 cells, suggesting that MIPEP may contribute to the maintenance of mitochondrial quality during CRvia activation of SIRT3. This novel mechanism of SIRT3 activation through MIPEP facilitates the elucidation of additional molecular pathways of CR