Cho Levels Research Articles

Effects of Zhishi Daozhi Decoction on the intestinal flora of nonalcoholic fatty liver disease mice induced by a high-fat diet.

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease with a high incidence, and the situation is not optimistic. Intestinal flora imbalance is strongly correlated with NAFLD pathogenesis. Zhishi Daozhi Decoction (ZDD) is a water decoction of the herbs used in the classical Chinese medicine prescription Zhishi Daozhi Pills. Zhishi Daozhi Pills has shown promising hepatoprotective and hypolipidemic properties, but its specific mechanism remains unclear. Mice were fed on a high fat-rich diet (HFD) for ten weeks, and then the animals were administrated ZDD through oral gavage for four weeks. The serum liver function and blood lipid indexes of the mice were then tested using an automatic biochemical analyzer. H&E and Oil Red O staining were used to observe the pathological conditions of mice liver tissue, and 16S rRNA sequencing technology was used to analyze the changes in intestinal flora of mice. The concentration of short-chain fatty acids (SCFAs) in the gut of mice was analyzed by gas chromatography-mass spectrometry (GC-MS). The expression of tight junction (TJ) proteins between ileal mucosal epithelial cells was analyzed using the immunofluorescence technique. ZDD was found to reduce the bodyweight of NAFLD mice, reduce serum TG, CHO, ALT, and AST levels, reduce fat accumulation in liver tissue, make the structure of intestinal flora comparable to the control group, and increase the concentration of intestinal SCFAs. It was also found to increase the expression of TJ proteins such as occludin and ZO-1, making them comparable to the control group. ZDD has a therapeutic effect on NAFLD mice induced by HFD, which may act by optimizing the intestinal flora structure.

Organization of neurochemical interactions in young and older brains as revealed with a network approach: Evidence from proton magnetic resonance spectroscopy (1H-MRS)

Aging is associated with alterations in the brain including structural and metabolic changes. Previous research has focused on neurometabolite level differences associated to age in a variety of brain regions, but the relationship among metabolites across the brain has been much less studied. Investigating these relationships can reveal underlying neurometabolic processes, their interdependency, and their progress throughout the lifespan. Using 1H-MRS, we investigated the relationship among metabolite concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-Inositol (mIns) and glutamate-glutamine complex (Glx) in seven voxel locations, i.e., bilateral sensorimotor cortex, bilateral striatum, pre-supplementary motor area, right inferior frontal gyrus and occipital cortex. These measurements were performed on 59 human participants divided in two age groups: young adults (YA: 23.2 ± 4.3; 18–34 years) and older adults (OA: 67.5 ± 3.9; 61–74 years). Our results showed age-related differences in NAA, Cho, and mIns across brain regions, suggesting the presence of neurodegeneration and altered gliosis. Moreover, associative patterns among NAA, Cho and Cr were observed across the selected brain regions, which differed between young and older adults. Whereas most of metabolite concentrations were inhomogeneous across different brain regions, Cho levels were shown to be strongly related across brain regions in both age groups. Finally, we found metabolic associations between homologous brain regions (SM1 and striatum) in the OA group, with NAA showing a significant correlation between bilateral sensorimotor cortices (SM1) and mIns levels being correlated between the bilateral striata. We posit that a network perspective provides important insights regarding the potential interactions among neurochemicals underlying metabolic processes at a local and global level and their relationship with aging.

An Effective Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Improves Sarcopenic Obesity in Obese Mice by Modulating Skeletal Muscle Metabolism.

PurposeThis study aimed to investigate the effect of Semaglutide on skeletal muscle and its metabolomics.MethodsA total of 18 male C57BL/6 mice were randomly divided into normal control (NC) group, high-fat diet (HFD) group and HFD+Semaglutide group, and were given standard diet, HFD diet, HFD diet plus Semaglutide, respectively. The body weight, gastrocnemius weight, serum lipid, blood glucose and inflammatory index levels of mice in each group were observed and compared, and the morphological and structural changes of gastrocnemius were also analyzed. Meanwhile, gastrocnemius metabolite changes were analyzed by untargeted metabolomics.ResultsAfter Semaglutide treatment, the food intake and body weight of mice were evidently decreased, while the relative gastrocnemius weight ratio were conversely increased. Meanwhile, the levels of TG, CHO, LDL, HDL, TNF-α, IL-6, IL-1β and HOMA-IR were all observed to decrease remarkably after Semaglutide intervention. Histological analysis showed that Semaglutide significantly improved the pathological changes of gastrocnemius, manifested as increased type I/type II muscle fiber ratio, total muscle fiber area, muscle fiber density, sarcomere length, mitochondrial number and mitochondrial area. Furthermore, metabolic changes of gastrocnemius after Semaglutide intervention were analyzed, and 141 kinds of differential metabolites were screened out, mainly embodied in lipids and organic acids, and enriched in 9 metabolic pathways including a variety of amino acids.ConclusionSemaglutide can significantly reduce the body weight and the accumulation of intramuscular fat, promote muscle protein synthesis, increase the relative proportion of skeletal muscle, and improve muscle function of obese mice, possibly by altering the metabolism of muscle lipids and organic acids.

Macromolecular-Suppressed GABA-Edited MR Spectroscopy in the Posterior Cingulate Cortex of Patients With Acute Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) causes a number of molecular and cellular alterations. There is evidence of an imbalance between the main excitatory (glutamate, Glu) and the main inhibitory (gamma-aminobutyric acid [GABA]) neurotransmitters following mTBI. In vivo human GABA-Glu balance studies following mTBI are sparse. To investigate the effect of acute mTBI on the GABA concentration measured in the posterior cingulate cortex (PCC) of pediatric patients by using the macromolecular (MM)-suppressed GABA J-editing technique. Prospective patient and phantom. A total of 14 pediatric patients (mean age 16.0 ± 1.7) with acute mTBI (<3 days after trauma; Glasgow Coma Scale 15) and 16 healthy volunteers (mean age 16.9 ± 2.8). Phantom: 524 cm3 sphere containing 10 mM glycine, 10 mM GABA. A 3 T, MEGA-PRESS pulse sequence. GABA spectra were processed in Gannet software. MM-suppressed GABA editing efficiency was derived from the phantom study. Absolute GABA and glutamate + glutamine (Glx) concentrations were quantified using different types of correction and compared between groups. N-acetyl aspartate (NAA) and choline (Cho) levels relative to tCr were also compared. Shapiro-Wilk test, Mann-Whitney U test, Student t-test, Pearson or Spearman correlations. P < 0.01 was considered statistically significant. The MM-suppressed GABA editing efficiency was 0.63. GABA signal fit error was <16% for all participants. The GABA concentration in the PCC of the mTBI group was significantly different from that in healthy controls: GABA/tCr was higher by 27%, absolute GABA concentration with different types of correction was higher by ≈17%. No significant differences were observed in Glx concentrations (P ≥ 0.32) or in Glx/tCr (P ≥ 0.1), NAA/tCr (P=0.55), and Cho/tCr levels (P=0.85). We report an increase in the GABA concentration in the PCC region in acute mTBI pediatric patients. This may suggest activation of GABA synthesis and impairment of the GABAergic system after acute mTBI. 3 TECHNICAL EFFICACY: Stage 1.

Effects of ibudilast on central and peripheral markers of inflammation in alcohol use disorder: A randomized clinical trial.

Ibudilast, a neuroimmune modulator, shows promise as a pharmacotherapy for alcohol use disorder (AUD). In vivo administration of ibudilast reduces the expression of pro-inflammatory cytokines in animal models, but its effects on markers of inflammation in humans are unknown. This preliminary study examined the effect of ibudilast on peripheral and potential central markers of inflammation in individuals with AUD. This study also explored the predictive relationship of neurometabolite markers with subsequent drinking in the trial. Non-treatment-seeking individuals with an AUD (n = 52) were randomized to receive oral ibudilast (n = 24) or placebo (n = 28) for 2 weeks. Plasma levels of peripheral inflammatory markers were measured at baseline and after 1 and 2weeks of medication. At study mid-point, proton magnetic resonance spectroscopy was performed to measure potential neurometabolite markers of inflammation: choline-compounds (Cho), myo-inositol (MI) and creatine + phosphocreatine (Cr) in frontal and cingulate cortices from 43 participants (ibudilast: n = 20; placebo: n = 23). The treatment groups were compared on peripheral and central markers. Ibudilast-treated participants had lower Cho in superior frontal white matter and nominally lower MI in pregenual anterior cingulate cortex. Ibudilast-treated participants had nominally lower C-reactive protein levels at visit 2 and nominally lower TNF-α/IL-10 ratios, relative to placebo. C-reactive protein and Cho levels were correlated, controlling for medication. Superior frontal white matter Cho predicted drinking in the following week. Micro-longitudinal ibudilast treatment may induce peripheral and putative central anti-inflammatory responses in patients with AUD. The neurometabolite responses may be associated with reduction in drinking, suggesting an anti-inflammatory component to the therapeutic action of ibudilast.

Effect of MAO-B Inhibitors on Neurometabolic Profile of Patients Affected by Parkinson Disease: A Proton Magnetic Resonance Spectroscopy Study.

Parkinson’s Disease (PD) is the most common neurodegenerative movement disorder whose treatment is symptomatic. No suitable methods for assessing the effects of dopaminergic drugs on disease progression in clinical trials have yet been provided. The aim of this longitudinal study is to evaluate the influence of rasagiline and selegiline on neurometabolic profile in de novo PD patients by using Proton Magnetic Resonance Spectroscopy (1H-MRS). We enrolled de novo PD patients who were divided into two groups of 20 patients each, according to the dopaminergic treatment prescribed at the baseline visit (rasagiline or selegiline). At the baseline visit and after 12 months, all patients underwent neurological evaluation as well as 1H-MRS. Forty healthy controls (HC) underwent 1H-MRS at baseline and after 12 months. PD patients, compared to HC, showed significantly lower concentrations of NAA in the motor cortex, while the Cho levels showed a decreasing trend. After 12 months of therapy, the 1H-MRS study revealed that rasagiline and selegiline in a similar way were able to restore the NAA levels to values similar to those of HC. In addition, this neurometabolic change showed a correlation with UPDRS-III scores. This is the first longitudinal study that provides preliminary evidence that 1H-MRS may be a suitable method to evaluate objectively the influence of MAO-B inhibitors on the neurometabolic profile of PD patients. These results could open a new scenario on the hypothesis of a drug-induced slowing effect of PD progression.

Comparing the histological effect of Thymol from multiple sources with blood lipids profile and liver enzymes in Albino Mice

The therapeutic value of the phenolic component and pure thymol was well known; this study comprised the extraction of crude phenol from two plants (Thymus vulgaris and Artemisia annua) which contain thymol with pure thymol and evaluate their effect on hematological and histological by using three different concentrations of each plant extract and pure thymol to tested them on lab mice. All the mice were allowed free access to water and feed for 21 days in laboratory conditions; orally, pure water was administered to the control mice (group I), while groups II, III, and IV were given orally with T. vulgaris, A. annua, combination of last two crude phenol plant extract 50:50 and pure thymol respectively. The levels of CHO, TRI, and HDL were significantly reduced in A. annua and T. vulgaris crude phenolic extract at 20 mg/ml as compared to the control treatment, while pure Thymol at 10 mg/ml gave the best result in reducing the levels of CHO, TRI, and HDL. In comparison to the control group, serum levels of liver enzymes in groups treated with in A. annua, T. vulgaris extract, and pure Thymol were substantially reduced in concentration: 20, 10 and 30 mg/ml, respectively.

Abstract 13196: Highly Active Antiretroviral Therapy-related Complications And Associated Genetic Susceptibility Variants In Hiv-infected Patients With Pre-existing Heart Failure: A 7-year Prospective Cohort Study

Introduction: HAART-associated metabolic syndromes have been reported, without such risk and genetic markers in patients with pre-existing heart failure (HF) being addressed. Hypothesis: We hypothesize that compared with HIV-infected patients without HF undergoing HAART, patients with pre-existing HF are at higher risk of long-term HAART-related metabolic complications, which is associated with genetic variants. Methods: In this prospective cohort study 172 HIV-infected patients were recruited and followed-up since 2013. Demographic and medical records such as weight, BMI, drug use, lab data of blood and urine, HAART regimens, Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) CVD risk scores, were recorded. Multivariate regression model was used to derive risk of adverse outcomes following HAART in HF patients, compared to matched-patients without HF. GWAS was conducted in HF patients to investigate genetic variants associated with adverse events susceptibility. Results: After matching on baseline, HAART was effective for both patients with or without HF, at a similar viral load (r=0.001, P=0.69) and CD4 count (r=-0.06, P=0.48). D:A:D (R) (r=0.002, P=0.97) and D:A:D (F) (r=0.04, P=0.62) CVD risk scores were comparable in patients with and without HF. Patients with HF presented with higher risks of subsequent T2DM (r = 0.24, P=0.01) and increased total cholesterol (r=0.23, P=0.006), LDL (r=0.18, P=0.04), and uric acid (r=0.35, P=0.004), compared to those without HF. Four independent SNPs in ABCG2 (rs717620), PNPLA3 (rs738409), CYP2A6 (rs28399433), and CYP2B6 (rs2279345) reached genome-wide significance for their associations with HAART-related complications in patients with HF, including ABCG2 for subsequent advanced stages CKD (eGFR &lt; 30), PNPLA3 for increased HDL levels, CYP2A6 for increased BUN levels, and CYP2B6 for hematuria. Conclusions: HAART was equally effective for HIV management in HF patients, and did not result in more subsequent cardiotoxicities, compared with those without HF; however, increased risk of T2DM, and increased levels of CHO, LDL, and uric acid during follow-ups, were observed. Genetic susceptibility variants associated with HAART-related complications in HF patients were demonstrated.

GuanXinNing Tablet Attenuates Alzheimer's Disease via Improving Gut Microbiota, Host Metabolites, and Neuronal Apoptosis in Rabbits.

Based on accumulating evidence, Alzheimer's disease (AD) is related to hypercholesterolemia, gut microbiota, and host metabolites. GuanXinNing Tablet (GXN) is an oral compound preparation composed of two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., both of which exert neuroprotective effects. Nevertheless, the effect of GXN on AD is unknown. In the present study, we investigated whether GXN alters cholesterol, amyloid-beta (Aβ), gut microbiota, serum metabolites, oxidative stress, neuronal metabolism activities, and apoptosis in an AD model rabbit fed a 2% cholesterol diet. Our results suggested that the GXN treatment significantly reduced cholesterol levels and Aβ deposition and improved memory and behaviors in AD rabbits. The 16S rRNA analysis showed that GXN ameliorated the changes in the gut microbiota, decreased the Firmicutes/Bacteroidetes ratio, and improved the abundances of Akkermansia and dgA-11_gut_group. 1H-NMR metabolomics found that GXN regulated 12 different serum metabolites, such as low-density lipoprotein (LDL), trimethylamine N-oxide (TMAO), and glutamate (Glu). In addition, the 1H-MRS examination showed that GXN remarkably increased N-acetyl aspartate (NAA) and Glu levels while reducing myo-inositol (mI) and choline (Cho) levels in AD rabbits, consequently enhancing neuronal metabolism activities. Furthermore, GXN significantly inhibited oxidative stress and neuronal apoptosis. Taken together, these results indicate that GXN attenuates AD via improving gut microbiota, host metabolites, and neuronal apoptosis.

YNCRG Alleviated Hepatic Steatosis in Metabolic Syndrome Model Rats by Improving Lipid Metabolism and Chronic Inflammatory Reaction

YNCRG is a combination of five traditional Chinese ingredients with medicinal properties. We studied its effects and mechanism of action on a rat model of non-alcoholic fatty liver with metabolic syndrome. Eight-week-old male SHRcp rat(s) and Wister Kyoto (WKY) rats were adaptively fed for one week, after which they were randomly divided into three groups, including the control group (n = 9), the YNCRG group (n = 8), and the WKY group (n = 8). The WKY group could freely consume water, the control group was provided water every day, and the YNCRG group was gavaged with an aqueous solution of YNCRG (3.6 g/kg body weight/day) for eight weeks. After eight weeks of intervention, YNCRG effectively reduced the weight of rats and significantly reduced the serum levels of AST, ALT, CHO, and TG compared to the weight of the rats in the control group. The RT-PCR results showed that mRNA levels of NF-κB, TLR4, TNF-α, and IL-1β increased, and the levels of MCP-1 and ICAM-1 also increased, but YNCRG effectively reduced the mRNA levels. The results of the Western blotting assay showed that YNCRG did not affect the AMPK/ACC signaling pathway, but it strongly promoted the phosphorylation of PKA, ERK, and C/EBPβ in rat livers. YNCRG also significantly promoted the phosphorylation of IRS-1 (Tyr465) but inhibited IRS-1 (Ser1101); both are upstream factors of ERK. We found that YNCRG can reduce the accumulation of lipids in the liver of rats with metabolic syndrome, probably by affecting lipid metabolism and the signaling pathway associated with inflammatory reactions.

Postprandial concentration of circulating branched chain amino acids are able to predict the carbohydrate content of the ingested mixed meal

The amount of the macronutrients protein and carbohydrate (CHO) in a mixed meal is known to affect each other's digestion, absorption, and subsequent metabolism. While the effect of the amount of dietary protein and fat on the glycemic response is well studied, the ability of postprandial plasma amino acid patterns to predict the meal composition is unknown. To study the postprandial plasma amino acid patterns in relation to the protein, CHO, and fat content of different mixed meals and to investigate if these patterns can predict the macronutrient meal composition. Ten older adults were given 9 meals with 3 different levels (low, medium, and high) of protein, CHO, and fat in different combinations, taking the medium content as that of a standardized western meal. We monitored the postprandial plasma response for amino acids, glucose, insulin, and triglycerides for 8h and the areas under the curve (AUC) were subsequently calculated. Multiple regression analysis was performed to determine if amino acid patterns could predict the meal composition. Increasing meal CHO content reduced the postprandial plasma response of several amino acids including all branched chain amino acids(BCAA) (leucine; q<0.0001, isoleucine; q=0.0035, valine; q=0.0022). The plasma BCAA patterns after the meal significantly predicted the meal's CHO content (leucine; p<0.0001, isoleucine; p=0.0003, valine; p=0.0008) along with aspartate (p<0.0001), tyrosine (p<0.0001), methionine (p=0.0159) and phenylalanine (p=0.0332). Plasma citrulline predicted best the fat content of the meal (p=0.0024). The postprandial plasma BCAA patterns are lower with increasing meal CHO content and are strong predictors of a mixed meal protein and CHO composition, as are plasma citrulline for the fat content. We hypothesize that postprandial plasma amino acid concentrations can be used to predict the meal's macronutrient composition.

Metabolic abnormality in acute stroke-like lesion and its relationship with focal cerebral blood flow in patients with MELAS: Evidence from proton MR spectroscopy and arterial spin labeling

Our purpose is to detect the metabolic alterations in acute stroke-like lesions (SLLs) and further investigate the correlations between metabolic concentrations and focal cerebral blood flow in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) using proton MR spectroscopy (1H-MRS) and arterial spin labeling (ASL). A total of 23 patients with MELAS at acute stage of stroke-like episodes (SLEs) and 20 normal controls (NC) were recruited in this study, respectively. All subjects underwent conventional MRI and1H-MRS. In addition, ASL was performed in each patient. The measurements of creatine (Cr), choline (Cho), N-acetyl aspartate (NAA), lactate (Lac), glutamine/glutamate (Glx) levels and the ratios of Cho/Cr, NAA/Cr, Lac/Cr and Glx/Cr in acute SLLs for MELAS patients and left parietal and occipital lobes for NC were measured using LC-model software. Furthermore, in MELAS group, the associations between relative cerebral blood flow (rCBF) and metabolite concentrations in acute SLLs were also assessed. In MELAS group, acute SLLs were identified with metabolic abnormalities and increased rCBF. Specifically, compared with controls, MELAS patients exhibited significantly higher Lac, Cho levels and Lac/Cr, Cho/Cr ratios, and lower NAA, Glx levels and NAA/Cr and Glx/Cr ratios. Moreover, for MELAS patients, Lac concentration in acute SLLs was positively correlated with focal rCBF. This study exhibited the neural injury with increasing lactate and cerebral blood flow in the acute SLEs. It might shed light on the underlying biochemical mechanism of mitochondrial cytopathy and angiopathy in MELAS.

Preliminary Findings Associate Hippocampal 1H-MR Spectroscopic Metabolite Concentrations with Psychotic and Manic Symptoms in Patients with Schizophrenia.

Previous hippocampal proton MR spectroscopic imaging distinguished patients with schizophrenia from controls by elevated Cr levels and significantly more variable NAA and Cho concentrations. This goal of this study was to ascertain whether this metabolic variability is associated with clinical features of the syndrome, possibly reflecting heterogeneous hippocampal pathologies and perhaps variability in its "positive" (psychotic) and "negative" (social and emotional deficits) symptoms. In a sample of 15 patients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, we examined the association of NAA and Cho levels with research diagnostic interviews and clinical symptom ratings of the patients. Metabolite concentrations were previously obtained with 3D proton MR spectroscopic imaging at 3T, a technique that facilitates complete coverage of this small, irregularly shaped, bilateral, temporal lobe structure. The patient cohort comprised 8 men and 7 women (mean age, 39.1 [SD, 10.8] years, with a mean disease duration of 17.2 [SD, 10.8] years. Despite the relatively modest cohort size, we found the following: 1) Elevated Cho levels predict the positive (psychotic, r = 0.590, P = .021) and manic (r = 0.686, P = .005) symptom severity; and 2) lower NAA levels trend toward negative symptoms (r = 0.484, P = .08). No clinical symptoms were associated with Cr level or hippocampal volume (all, P ≥ .055). These preliminary findings suggest that NAA and Cho variations reflect different pathophysiologic processes, consistent with microgliosis/astrogliosis and/or lower vitality (reduced NAA) and demyelination (elevated Cho). In particular, the active state-related symptoms, including psychosis and mania, were associated with demyelination. Consequently, their deviations from the means of healthy controls may be a marker that may benefit precision medicine in selection and monitoring of schizophrenia treatment.

Efficacy of Lidan Tang on high-fat-diet induced hepatolithiasis in mice and possible mechanism.

To investigate efficacy of Lidan Tang (LDT) on gallstone induced by high fat diet in mice, and to study its underlying mechanism. Mice were fed with high fat diet every day and treated with LDT (9.01 times of human clinic dosage). Mice were randomly divided into 6 groups as control group, gallstone model group (high-fat diet), positive control ursodeoxycholic acid (UDCA) group (80 mg·kg-1·d-1, i.g.), LDT low dose group (6 kg/d, i.g.), LDT middle dose group (12 kg/d, i.g.), and LDT high dose group (24 kg/d, i.g.). The whole experiment was lasted for 4 weeks. The levels of ALT, AST, LDH, CHO, HDL-C and LDL-C in serum were measured, the pathological sections were observed by hematoxylin-eosin staining, the activities of antioxidant enzymes were measured by kits, and the proteins related to oxidative stress and lipid transport were detected by Western blot analysis. LDT could significantly reduce the contents of ALT and AST in serum and improve the pathological tissue of liver. LDT could significantly reduce the content of MDA and LPO, and increase the level of GSH and GSH-PX in liver tissue. The data of Western blot showed that LDT had antioxidant effect promoting Keap1/Nrf2 pathway and regulated the process of lipid transport, which was statistically significant. In addition, LDT treatment inhibited the expression of ATP-binding cassette transports ABCG5/8 in liver, and reduced cholesterol transport from the hepatocytes to the gallbladder. LDT has protective effect on gallstones induced by high fat diet in mice, which might be based on the protective effect on liver, including enhancing the antioxidant capacity of liver and reducing the production of lipid peroxides.

Effect of High-Intensity Interval Training with Eryngium Campestre on Lipid Profile and Glycemic Indices in High-Fat Diet-Induced Obese Rats

Background: Obesity is a multi-factorial physical disorder that results in high serum lipid levels and glycemic disorders. On the other hand, regular exercise and administration of Eryngium Campestre (EC) have glucose and lipid-lowering effects. Objectives: The present study aimed to review the effect of high-intensity interval training (HIIT) with EC on lipid profile and glycemic indices in high-fat diet (HFD)-induced obese rats. Methods: Twenty-four obese rats were divided into four groups, including: (1) control, (2) HIIT, (3) EC, and (4) HIIT+EC. To investigate the effect of obesity on research variables, six rats were assigned to a healthy control group. During six weeks, groups 2 and 4 received HIIT three days per week, and groups 3 and 4 received 30 mg/kg EC by gavage. Data were analyzed using the Shapiro-Wilk test and one-way ANOVA with Tukey’s post hoc test (P ≤ 0.05). Results: Obesity significantly increased cholesterol (Cho), triglyceride (TG), insulin, and glucose levels (P ≤ 0.05). However, HIIT significantly decreased Cho, TG, insulin, and glucose levels (P ≤ 0.05), and EC significantly decreased Cho, TG, low-density lipoprotein (LDL), insulin, and glucose levels (P ≤ 0.05). Besides, HIIT+EC significantly decreased LDL and insulin (P ≤ 0.05). HIIT+EC could decrease LDL more than did HIIT (P ≤ 0.05). Conclusions: Although HIIT and EC alone improved the lipid profile and glycemic indices in obese rats, HIIT combined with EC had greater effects on the decrease of LDL compared to HIIT.

Metabolite abnormalities in psychosis risk: A meta-analysis of proton magnetic resonance spectroscopy studies.

Accumulating evidence implicates that individuals at high-risk of psychosis have already exhibited pathophysiological changes in brain metabolites including glutamate, gamma-Aminobutyric Acid (GABA), N-Acetylaspartate (NAA), creatine (Cr), myo-inositol (MI) and choline (Cho). These changes may contribute to the development of schizophrenia and associate with psychotic genes. However, specific metabolic changes of brain sub-regions in individuals at risk have still been controversial. Thus, the current study aimed to investigate the brain metabolic changes including glutamate, Glx, GABA, GABA/Glx, NAA, Cr, MI and Cho levels in individuals at risk by conducting a case-control meta-analysis and meta-regression of proton magnetic resonance spectroscopy studies. Primary outcomes revealed that individuals at risk exhibited increased Cr levels at the rostral medial prefrontal cortex (rmPFC), decreased NAA and Cr levels at the thalamus, and increased MI levels at the dorsolateral prefrontal cortex. Sub-group analyses further indicated that individuals with clinical high-risk (CHR) exhibited increased Cr levels at the medial prefrontal cortex (mPFC) and decreased Glx levels at the thalamus, while individuals with genetic risk (siblings of psychiatric patients) exhibited significant increased Glx and MI levels at the mPFC. However, GABA, GABA/Glx and Cho levels showed no significant result. These findings suggest that the dysfunctional metabolites at the mPFC and the thalamus may be an essential neurobiological basis at the early stage of psychosis.

Interactions of Blood Serum, Urine and Fecal Metabolites of Cats Fed by Different Dietary Protein and Carbohydrate Levels

Abstract Objectives Because dietary protein and carbohydrate levels impact the gastrointestinal (GI) microbiome and host metabolism, this study evaluated their effect on serum, urine and fecal metabolites. Methods Three complete and balanced isocaloric foods (mean 3940 kcals/kg) were used. Their protein (P) and carbohydrate (CHO) levels were: LP (P: 25.84%, CHO: 46.9%), MP (P: 32.0%, CHO: 39.9%) and HP (P: 50.67%, CHO: 21.2%). The study used 30 adult healthy cats and a balanced Latin-Square design. Food offering was adjusted to maintain weight; cats were fed for 80 days before receiving the next food. This study was reviewed and approved by IACUC and all cats included in this study were allowed routine social activities. Serum (S), urine (U) and fecal (F) samples were collected at the end of each treatment period and analyzed for non-targeted metabolomics by Metabolon Inc. (Morrisville, NC). Data analysis was performed by using JMP v14.0. Variables with significance at P &amp;lt; 0.05 are reported. Results PCA analysis of S, U and F metabolites together shows that the cats fed HP clustered separately from the cats fed LP and MP foods. Independent PCA analysis of S, U and F metabolites revealed that F metabolites show clear separation from the cats fed HP compared with LP and MP foods. However, S and U metabolites did not show this. Fecal samples showed that carbohydrates, acylglycerols, endocannabinoids and bile acids metabolism was significantly impacted by HP when compared with LP and MP foods. This resulted in elevations of a number of toxic metabolites (e.g., 3-indoxyl sulfate, p-cresol sulfate and trimethylamine N-oxide). The F concentration of these metabolites was positively correlated to that of S and U. This positive relationship in all three sample types was not observed for acylglycerols, endocannabinoids and sugars suggesting that those metabolites were not absorbed and excreted as were the mentioned toxins. Conclusions Dietary P and CHO levels influence cat's GI metabolism with impacting specific urine and serum metabolites. Cats fed HP food had F increases of toxic metabolites related to renal and cardiovascular disorders and these metabolites were positively associated with S and U concentrations. Dietary P and CHO levels may directly impact renal and cardiovascular disorders. Funding Sources Hill's Pet Nutrition, Inc.

Intermittent theta-burst stimulation moderates interaction between increment of N-Acetyl-Aspartate in anterior cingulate and improvement of unipolar depression

BackgroundIntermittent theta-burst stimulation (iTBS), a novel repetitive transcranial magnetic stimulation (rTMS) technique, appears to have antidepressant effects when applied over left dorsolateral prefrontal cortex (DLPFC). However, its underlying neurobiological mechanisms are unclear. Proton magnetic resonance spectroscopy (1H-MRS) provides in vivo measurements of cerebral metabolites altered in major depressive disorder (MDD) like N-acetyl-aspartate (NAA) and choline-containing compounds (Cho). We used MRS to analyse effects of iTBS on the associations between the shifts in the NAA and Cho levels during therapy and MDD improvement. MethodsIn-patients with unipolar MDD (N = 57), in addition to treatment as usual, were randomized to receive 20 iTBS or sham stimulations applied over left DLPFC over four weeks. Single-voxel 1H-MRS of the anterior cingulate cortex (ACC) was performed at baseline and follow-up. Increments of concentrations, as well as MDD improvement, were defined as endpoints. We tested a moderated mediation model of effects using the PROCESS macro (an observed variable ordinary least squares and logistic regression path analysis modeling tool) for SPSS. ResultsImprovement of depressive symptoms was significantly associated with decrease of Cho/NAA ratio, mediated by NAA. iTBS had a significant moderating effect enhancing the relationship between NAA change and depression improvement. ConclusionsOur findings suggest a potential neurochemical pathway and mechanisms of antidepressant action of iTBS, which may moderate the improvement of metabolic markers of neuronal viability. iTBS might increase neuroplasticity, thus facilitating normalization of neuronal circuit function.

Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study.

Liver cirrhosis (LC) can develop hepatocellular carcinoma (HCC). However, noninvasive early diagnosis of HCCs in the cirrhotic liver is still challenging. We aimed to quantify the hepatic metabolites in normal control (NC), cirrhotic liver without HCC, cirrhotic liver with HCC (CLH), and early-stage HCC groups using proton magnetic resonance spectroscopy (1H-MRS) with a long echo-time (TE) and to assess the potential association between the levels of hepatic metabolites in these four groups and aging and enzymatic activity. Thirty NCs, 30 viral hepatitis-induced LC patients without HCC, and 30 viral hepatitis-induced LC patients with HCC were included in this study. 1H-MRS measurements were performed on a localized voxel of the normal liver parenchyma (n = 30) from NCs, cirrhotic liver parenchyma (n = 30) from LC patients without HCC, and each of the cirrhotic liver parenchyma (n = 30) and HCC (n = 30) from the same patients in the CLH group. Generalized estimating equations were used to evaluate potential risk factors for changes in metabolite levels. Potential associations between metabolite levels and age and serum enzymatic activities were assessed by correlation analysis. The levels of lactate+triglyceride (Lac+TG) and choline (Cho) in HCC were significantly higher compared to those in LC and CLH. A potential risk factor for changes in the Lac+TG and Cho levels was age, specifically 60–80 years of age. In particular, the Lac+TG level was associated with a high odds ratio of HCC in males aged 60–80 years. The Lac+TG and Cho concentrations were positively correlated with lactate dehydrogenase and alkaline phosphatase activities, respectively. Our findings suggested that 1H-MRS measurement with a long TE was useful in quantifying hepatic Lac+TG and Cho levels, where higher Lac+TG and Cho levels were most likely associated with HCC-related metabolism in the viral hepatitis-induced cirrhotic liver. Further, the level of Lac+TG in HCC was highly correlated with older age and lactate dehydrogenase activity.

Effects of Fish Oil Monotherapy on Depression and Prefrontal Neurochemistry in Adolescents at High Risk for Bipolar I Disorder: A 12-Week Placebo-Controlled Proton Magnetic Resonance Spectroscopy Trial.

Objectives: To evaluate the clinical and neurochemical effects of 12-week fish oil, a source of omega-3 polyunsaturated fatty acids (n-3 PUFAs), in depressed adolescents with a family history of bipolar I disorder. Methods: Adolescents with a current Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision diagnosis of Major Depressive Disorder or Depressive Disorder not otherwise specified, a Childhood Depression Rating Scale-Revised (CDRS-R) Version raw score of ≥40, and at least one biological parent with bipolar I disorder were randomized to double-blind treatment with fish oil (2100 mg/day) or placebo for 12 weeks. The primary outcome measure was change in CDRS-R total score, and secondary outcomes measures were change in manic symptoms (Young Mania Rating Scale), global symptom and functioning measures (Clinical Global Impression-Severity [CGI-S] /CGI Improvement [CGI-I], Children's Global Assessment Scale, and Child Behavior Checklist), safety and laboratory measures, and anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex neurometabolite concentrations using proton magnetic resonance spectroscopy at 4 T. Results: Fifty-six patients were randomized, and 42 completed the 12-week trial (placebo: n = 21; fish oil, n = 21). Subjects randomized to fish oil, but not placebo, exhibited a significant baseline to endpoint increase in erythrocyte n-3 PUFAs. Reductions in CDRS-R scores did not differ between treatment groups (p = 0.15), and similar remission (p = 0.58) and response (p = 0.77) rates were observed. Fish oil produced a significantly greater decrease in CGI-S (p = 0.0042) and CGI-I (p = 0.036) scores compared with placebo. Baseline to endpoint change in ACC creatine (p = 0.004) and ACC choline (Cho) (p = 0.024) differed significantly between groups. Baseline ACC Cho levels were inversely correlated with baseline and baseline to endpoint change in CDRS-R scores, and baseline to endpoint change in ACC Cho correlated with baseline-endpoint change in CDRS-R scores and n-3 PUFA. There were no group differences in safety and tolerability ratings or laboratory measures. Conclusions: Fish oil monotherapy was not superior to placebo for reducing depressive symptoms in high-risk youth as assessed by the CDRS-R, but was safe and well tolerated and superior to placebo on clinician ratings of global symptom improvement. Associations among ACC Cho levels, depression symptom severity, and n-3 PUFA warrant additional investigation.