Branched-chain amino acids prevent obesity by inhibiting the cell cycle in an NADPH-FTO-mA coordinated manner.

Obesity has become a major health crisis in the past decades. Branched-chain amino acids (BCAA), a class of essential amino acids, exerted beneficial health effects with regard to obesity and its related metabolic dysfunction, although the underlying reason is unknown. Here, we show that BCAA supplementation alleviates high-fat diet (HFD)-induced obesity and insulin resistance in mice and inhibits adipogenesis in 3T3-L1 cells.

mRNA mC inhibits adipogenesis and promotes myogenesis by respectively facilitating YBX2 and SMO mRNA export in ALYREF-mC manner.

Although 5-methylcytosine (mC) has been identified as a novel and abundant mRNA modification and associated with energy metabolism, its regulation function in adipose tissue and skeletal muscle is still limited. This study aimed at investigating the effect of mRNA mC on adipogenesis and myogenesis using Jinhua pigs (J), Yorkshire pigs (Y) and their hybrids Yorkshire-Jinhua pigs (YJ). We found that Y grow faster than J and YJ, while fatness-related characteristics observed in Y were lower than those of J and YJ.

Metformin combats obesity by targeting FTO in an mA-YTHDF2-dependent manner.

Obesity has become a health threat and hard enough to deal with. Evidences show that metformin could inhibit adipogenesis and combat obesity, while its mechanisms remain to be elucidated more comprehensively. In this study, we found that administration of metformin could combat obesity of mice induced by high-fat diet (HFD), indicated by strikingly decreased body weight and weight of inguinal white adipose tissue (iWAT) and epidydimal white adipose tissue (eWAT) compared with the control group.

DHA alleviates diet-induced skeletal muscle fiber remodeling via FTO/mA/DDIT4/PGC1α signaling.

Background: Obesity leads to a decline in the exercise capacity of skeletal muscle, thereby reducing mobility and promoting obesity-associated health risks. Dietary intervention has been shown to be an important measure to regulate skeletal muscle function, and previous studies have demonstrated the beneficial effects of docosahexaenoic acid (DHA; 22:6 ω-3) on skeletal muscle function. At the molecular level, DHA and its metabolites were shown to be extensively involved in regulating epigenetic modifications, including DNA methylation, histone modifications, and small non-coding microRNAs.

FTO knockout in adipose tissue effectively alleviates hepatic steatosis partially via increasing the secretion of adipocyte-derived IL-6.

Objective: Adipose dysfunction affects the secretion of adipokines and mediates the hepatic physiological changes. Fat mass and obesity associated protein (FTO) plays a crucial part in fat deposition but the crosstalk between FTO-mediated secretion of adipokines and hepatic steatosis is not clear.

Methods: Firstly, adipose-selective FTO knockout (FTO) and control (FTO) mice were induced by high fat diet (HFD).

mRNA m5C controls adipogenesis by promoting CDKN1A mRNA export and translation.

5-Methylcytosine (mC) is a type of RNA modification that exists in tRNAs and rRNAs and was recently found in mRNA. Although mRNA mC modification has been reported to regulate diverse biological process, its function in adipogenesis remains unknown. Here, we demonstrated that knockdown of NOL1/NOP2/Sun domain family member 2 (NSUN2), a mC methyltransferase, increased lipid accumulation of 3T3-L1 preadipocytes through accelerating cell cycle progression during mitotic clonal expansion (MCE) at the early stage of adipogenesis.

m6A methylation promotes white-to-beige fat transition by facilitating Hif1a translation.

Obesity mainly results from a chronic energy imbalance. Promoting browning of white adipocytes is a promising strategy to enhance energy expenditure and combat obesity. N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an important role in regulating adipogenesis.

Curcumin prevents obesity by targeting TRAF4-induced ubiquitylation in m A-dependent manner.

Obesity has become a major health problem that has rapidly prevailed over the past several decades worldwide. Curcumin, a natural polyphenolic compound present in turmeric, has been shown to have a protective effect on against obesity and metabolic diseases. However, its underlying mechanism remains largely unknown.

Effect of citalopram on hippocampal volume in first-episode schizophrenia: Structural MRI results from the DECIFER trial.

Hippocampal volume loss is prominent in first episode schizophrenia (FES) and has been associated with poor clinical outcomes and with BDNF genotype; antidepressants are believed to reverse hippocampal volume loss via release of BDNF. In a 12-month, placebo-controlled add-on trial of the antidepressant, citalopram, during the maintenance phase of FES, negative symptoms were improved with citalopram. We now report results of structural brain imaging at baseline and 6 months in 63 FES patients (34 in citalopram group) from the trial to assess whether protection against hippocampal volume loss contributed to improved negative symptoms with citalopram.

Association of Aripiprazole With Reduced Hippocampal Atrophy During Maintenance Treatment of First-Episode Schizophrenia.

Purpose/background: Hippocampal volume loss in early schizophrenia has been linked with markers of inflammation and oxidative stress, and with less response of negative symptoms. Aripiprazole has been reported to preserve hippocampal volume and to reduce inflammation.

Methods/procedures: Study 1 was a 12-month multicenter randomized placebo-controlled trial of citalopram added to clinician-determined second-generation antipsychotic medication in 95 patients with first-episode schizophrenia (FES), 19 of whom received aripiprazole.

Effect of DAOA genetic variation on white matter alteration in corpus callosum in patients with first-episode schizophrenia.

D-amino acid oxidase activator (DAOA) gene, which plays a crucial role in the process of glutamatergic transmission and mitochondrial function, is frequently linked with the liability for schizophrenia. We aimed to investigate whether the variation of DAOA rs2391191 is associated with alterations in white matter integrity of first-episode schizophrenia (FES) patients; and whether it influences the association between white matter integrity, cognitive function and clinical symptoms of schizophrenia. Forty-six patients with FES and forty-nine healthy controls underwent DTI and were genotyped for DAOA rs2391191.

Air pollution and hippocampal atrophy in first episode schizophrenia.

Air pollution has recently been linked to central nervous system (CNS) diseases, possibly mediated by inflammation and oxidative stress. Hippocampal atrophy in individuals with first episode schizophrenia (FES) has also been associated with biomarkers of inflammation and oxidative stress, whereas hippocampal atrophy was not observed in matched healthy controls with similar biomarker levels of inflammation and oxidative stress. Fine particulate matter (PM2.

Parietal memory network and default mode network in first-episode drug-naïve schizophrenia: Associations with auditory hallucination.

Atypical spontaneous activities in resting-state networks may play a role in auditory hallucinations (AHs), but networks relevant to AHs are not apparent. Given the debating role of the default mode network (DMN) in AHs, a parietal memory network (PMN) may better echo cognitive theories of AHs in schizophrenia, because PMN is spatially adjacent to the DMN and more relevant to memory processing or information integration. To examine whether PMN is more relevant to AHs than DMN, we characterized these intrinsic networks in AHs with 59 first-episode, drug-naïve schizophrenics (26 AH+ and 33 AH-) and 60 healthy participants in resting-state fMRI.

Anterior Hippocampal-Cortical Functional Connectivity Distinguishes Antipsychotic Naïve First-Episode Psychosis Patients From Controls and May Predict Response to Second-Generation Antipsychotic Treatment.

Background: Converging evidence implicates the anterior hippocampus in the proximal pathophysiology of schizophrenia. Although resting state functional connectivity (FC) holds promise for characterizing anterior hippocampal circuit abnormalities and their relationship to treatment response, this technique has not yet been used in first-episode psychosis (FEP) patients in a manner that distinguishes the anterior from posterior hippocampus.

Methods: We used masked-hippocampal-group-independent component analysis with dual regression to contrast subregional hippocampal-whole brain FC between healthy controls (HCs) and antipsychotic naïve FEP patients (N = 61, 36 female).

Citalopram in first episode schizophrenia: The DECIFER trial.

Antidepressants are frequently prescribed in first episode schizophrenia (FES) patients for negative symptoms or for subsyndromal depressive symptoms, but therapeutic benefit has not been established, despite evidence of efficacy in later-stage schizophrenia. We conducted a 52 week, placebo-controlled add-on trial of citalopram in patients with FES who did not meet criteria for major depression to determine whether maintenance therapy with citalopram would improve outcomes by preventing or improving negative and depressive symptoms. Primary outcomes were negative symptoms measured by the Scale for Assessment of Negative Symptoms and depressive symptoms measured by the Calgary Depression Scale for Schizophrenia; both were analyzed by an intent-to-treat, mixed effects, area-under-the-curve analysis to assess the cumulative effects of symptom improvement and symptom prevention over a one-year period.

Association between catechol-O-methyltransferase genetic variation and functional connectivity in patients with first-episode schizophrenia.

Dopamine in the prefrontal cortex (PFC) plays an important role in cognitive performance and regulates by catechol-O-methyltransferase (COMT) expression. To clarify the effect of COMT genotype on cognitive function in patients with schizophrenia, we performed DNA genotyping, cognitive evaluations, and functional magnetic resonance imaging (fMRI) in antipsychotic-naïve patients with first-episode schizophrenia (FES) and matched healthy control subjects. We found that all cognitive domains were impaired in patients with FES compared with healthy subjects.

Association of Hippocampal Atrophy With Duration of Untreated Psychosis and Molecular Biomarkers During Initial Antipsychotic Treatment of First-Episode Psychosis.

Importance: Duration of untreated psychosis (DUP) has been associated with poor outcomes in schizophrenia, but the mechanism responsible for this association is not known.

Objectives: To determine whether hippocampal volume loss occurs during the initial 8 weeks of antipsychotic treatment and whether it is associated with DUP, and to examine molecular biomarkers in association with hippocampal volume loss and DUP.

Design, Setting, And Participants: A naturalistic longitudinal study with matched healthy controls was conducted at Shanghai Mental Health Center.

Reduced -Aminobutyric Acid and Glutamate+Glutamine Levels in Drug-Naïve Patients with First-Episode Schizophrenia but Not in Those at Ultrahigh Risk.

Altered -aminobutyric acid (GABA), glutamate (Glu) levels, and an imbalance between GABAergic and glutamatergic neurotransmissions have been involved in the pathophysiology of schizophrenia. However, it remains unclear how these abnormalities impact the onset and course of psychosis. In the present study, 21 drug-naïve subjects at ultrahigh risk for psychosis (UHR), 16 drug-naïve patients with first-episode schizophrenia (FES), and 23 healthy controls (HC) were enrolled.

Abnormal white matter microstructure in drug-naive first episode schizophrenia patients before and after eight weeks of antipsychotic treatment.

Background: Abnormal white matter integrity has been reported among first episode schizophrenia patients. However, findings on whether it can be reversed by short-term antipsychotic medications are inconsistent.

Method: Diffusion tensor imaging (DTI) was obtained from 55 drug-naive first episode schizophrenia patients and 61 healthy controls, and was repeated among 25 patients and 31 controls after 8 weeks during which patients were medicated with antipsychotics.

Prolonged cortical silent period among drug-naive subjects at ultra-high risk of psychosis.

Background: Deficits in gamma-aminobutyric acid (GABA) inhibitory neurotransmission have been associated with pathophysiological mechanisms underlying schizophrenia. However, little is known about whether these deficits occur before or after the onset of psychosis.

Method: We recruited 16 drug-naive subjects at ultra-high risk of psychosis (UHR), 17 schizophrenia patients and 28 healthy controls.