Occurrence Of Metabolic Diseases Research Articles

Akkermansia muciniphila: a potential candidate for ameliorating metabolic diseases.

Metabolic diseases are comprehensive disease based on obesity. Numerous cumulative studies have shown a certain correlation between the fluctuating abundance of Akkermansia muciniphila and the occurrence of metabolic diseases. A. muciniphila, a potential probiotic candidate colonized in the human intestinal mucus layer, and its derivatives have various physiological functions, including treating metabolic disorders and maintaining human health. This review systematically explicates the abundance change rules of A. muciniphila in metabolic diseases. It also details the high efficacy and specific molecules mechanism of A. muciniphila and its derivatives in treating obesity, type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease.

Research Progress on Extraction and Detection Technologies of Flavonoid Compounds in Foods.

Flavonoid compounds have a variety of biological activities and play an essential role in preventing the occurrence of metabolic diseases. However, many structurally similar flavonoids are present in foods and are usually in low concentrations, which increases the difficulty of their isolation and identification. Therefore, developing and optimizing effective extraction and detection methods for extracting flavonoids from food is essential. In this review, we review the structure, classification, and chemical properties of flavonoids. The research progress on the extraction and detection of flavonoids in foods in recent years is comprehensively summarized, as is the application of mathematical models in optimizing experimental conditions. The results provide a theoretical basis and technical support for detecting and analyzing high-purity flavonoids in foods.

Investigation and Analysis of Dietary Habits and the Occurrence of Metabolic Diseases (Lintao County)

Investigation and Analysis of Dietary Habits and the Occurrence of Metabolic Diseases (Lintao County)

Recent Advances in Hepatic Metabolic Regulation by the Nuclear Factor Rev-erbɑ.

Rev-erbɑ (NR1D1) is a nuclear receptor superfamily member that plays a vital role in mammalian molecular clocks and metabolism. Rev-erbɑ can regulate the metabolism of drugs and the body's glucose metabolism, lipid metabolism, and adipogenesis. It is even one of the important regulatory factors regulating the occurrence of metabolic diseases (e.g., diabetes, fatty liver). Metabolic enzymes mediate most drug metabolic reactions in the body. Rev-erbɑ has been recognized to regulate drug metabolic enzymes (such as Cyp2b10 and Ugt1a9). Therefore, this paper mainly reviewed that Rev-erbɑ regulates I and II metabolic enzymes in the liver to affect drug pharmacokinetics. The expression of these drug metabolic enzymes (up-regulated or down-regulated) is related to drug exposure and effects/ toxicity. In addition, our discussion extends to Rev-erbɑ regulating some transporters (such as P-gp, Mrp2, and Bcrp), as they also play an essential role in drug metabolism. Finally, we briefly describe the role and mechanism of nuclear receptor Rev-erbɑ in lipid and glucose homeostasis, obesity, and metabolic disorders syndrome. In conclusion, this paper aims to understand better the role and mechanism of Rev-erbɑ in regulating drug metabolism, lipid, glucose homeostasis, obesity, and metabolic disorders syndrome, which explores how to target Rev-erbɑ to guide the design and development of new drugs and provide scientific reference for the molecular mechanism of new drug development, rational drug use, and drug interaction.

Diet Quality Variation among Polish Older Adults: Association with Selected Metabolic Diseases, Demographic Characteristics and Socioeconomic Status.

A lot of civilization diseases are related to a low-quality diet, which is often determined by environmental factors. The aim of the present study was to assess the relationship between the quality of diet and the selected metabolic diseases, as well as demographic characteristics and socioeconomic status among Polish seniors. The study was conducted on the basis of the KomPAN questionnaire (Questionnaire for Dietary Views and Habits). The research sample was chosen arbitrarily. In addition, in order to diversify the research sample, the use of the snowball method was used. The study was conducted from June to September 2019 in a group of 437 people aged 60 or more years in two regions of Poland. Two diet quality indices with a potentially beneficial (pHDI-10) and adverse impact on health (pHDI-14) were selected based on data on the frequency of consumption of 24 food groups using the KomPAN questionnaire data development procedure. Based on the intensities (low, moderate, high) and combinations of these indices, three diet quality index profiles were developed with potentially different influences on health: lower (lowest), middle (intermediate) and upper (highest). Logistic regression was used to evaluate the relationship between diet quality indices, some metabolic diseases (obesity, arterial hypertension, diabetes type 2), demographic characteristics (gender, age, place of residence), and socioeconomic status (low, moderate, high). It was shown that in the examined seniors with selected metabolic diseases, the higher quality diet was more common among women, urban inhabitants and subjects with higher socioeconomic status. In turn, among the elderly with obesity, a high-quality diet was observed more often in people aged 60-74 years and those with type II diabetes at ages 75 years or more. The relationships between diet quality, demographic characteristics and socioeconomic status were demonstrated, but it was not possible to obtain unambiguous results on the relationship of these variables with the occurrence of metabolic diseases. Further extended studies should assess the importance of diet quality in reducing the risk of metabolic diseases in the elderly, taking into account the variability resulting from the environmental characteristics of the study population.

Lifestyle and Health-Related Quality of Life Relationships Concerning Metabolic Disease Phenotypes on the Nutrimdea Online Cohort.

Obesity, diabetes and cardiovascular events are non-communicable diseases (NCDs) directly related to lifestyle and life quality. Rises on NCDs rates are leading to increases in early deaths concerning metabolic morbidities. Health-related quality of life (HRQoL) has been described as a subjective perception about the influence of health and personal features on human well-being. This study aimed to characterize phenotypic and lifestyle roles on the occurrence of metabolic diseases and determine the potential mutual interactions and with HRQoL. Data from an online adult population (NUTRiMDEA study, n = 17,332) were used to estimate an adapted Obesogenic Score (ObS), while logistic regression analyses were fitted in order to examine relevant factors related to the prevalence of different metabolic diseases including HRQoL. Sex and age showed significant differences depending on lifestyle and metabolic health (p < 0.05). Adherence to the Mediterranean diet and physical activity showed a mutual interaction concerning ObS (p < 0.001), as well with metabolic health (p = 0.044). Furthermore, metabolic diseases showed own features related to sociodemographic and lifestyle characteristics in this population. Metabolic syndrome components may be differently influenced by diverse lifestyle or socioeconomic factors which in turn affect the perceived HRQoL. These outcomes should be taken into account individually for a precision medicine and public health purposes.

A method for quantifying hepatic and intestinal ceramides on mice by UPLC-MS/MS

BackgroundCeramide is one type of sphingolipids, is associated with the occurrence of metabolic diseases, including obesity, diabetes, cardiovascular disease, cancer, and nonalcoholic fatty liver disease. Dihydroceramide, the direct precursors of ceramide, which is converted to ceramide with the dihydroceramide desaturase, is recently regarded as involving in various biological processes and metabolic diseases. The liver and gut ceramide levels are interactional in pathophysiological condition, quantifying hepatic and intestinal ceramide levels become indispensable. The aim of this study is to establish a rapid method for the determination of ceramides including dihydroceramides in liver and small intestinal tissues for researching the mechanisms of ceramide related diseases. MethodsThe levels of Cer d18:1/2:0, Cer d18:1/6:0, Cer d18:1/12:0, Cer d18:1/14:0, Cer d18:1/16:0, Cer d18:1/17:0, Cer d18:1/18:0, Cer d18:1/20:0, Cer d18:1/22:0, Cer d18:1/24:1, Cer d18:1/24:0, dHCer d18:0/12:0, dHCer d18:0/14:0, dHCer d18:0/16:0, dHCer d18:0/18:0, dHCer d18:0/24:1 and dHCer d18:0/24:0 in mice liver and small intestine were directly quantified by ultra-high performance liquid chromatography-tandem mass spectrometry after methanol extraction. In detail, liver or small intestine tissues were thoroughly homogenized with methanol. The resultant ceramides were separated on a Waters BEH C18 column using gradient elution within 10 min. Positive electrospray ionization with multiple reaction monitoring was applied to detect. In the end, the levels of ceramides in mice liver and small intestine tissues were quantified by this developed method. ResultsThe limits of detection and quantification of 11 ceramides and 6 dihydroceramides were 0.01–0.5 ng/mL and 0.02–1 ng/mL, respectively, and all detected ceramides had good linearities (R2 > 0.997). The extraction recoveries of ceramides at three levels were within 82.32%–115.24% in the liver and within 83.21%–118.70% in the small intestine. The relative standard deviations of intra- and inter-day precision were all within 15%. The extracting solutions of the liver and small intestine could be stably stored in the autosampler 24 h at 10 °C, the lyophilized liver and small intestine for ceramides quantification could be stably stored at least 1 week at −80 °C. The ceramides and dihydroceramides in normal mice liver and small intestinal tissues analyzed by the developed method indicated that the detected 9 ceramide and 5 dihydroceramides levels were significantly different, in which Cer d18:1/16:0, Cer d18:1/22:0, Cer d18:1/24:1, Cer d18:1/24:0 and dHCer d18:0/24:1 are the main components in the liver, whereas Cer d18:1/16:0 and dHCer d18:0/16:0 accounts for the majority of proportion in the intestinal tissues. ConclusionA simple and rapid method for the quantification of 11 ceramides and 6 dihydroceramides in the animal tissues was developed and applied. The compositions of ceramides in two tissues suggested that the compositional features should to be considered when exploring the biomarkers or molecular mechanisms.

The link between prenatal stress and indicators of fatness in children – literature review

Background: There are indications that the occurrence of metabolic diseases in children may be conditioned by factors experienced already in the utero. Aim of the study: The aim of this systematic review was to analyze the studies that examined the effects of stress experienced by a pregnant woman on the child's adiposity rates in postnatal life. Methods: The review includes 20 articles published before March 2020 in Scopus and Medline databases with the use of following keyword combinations: /maternal or mother/, /prenatal or pregnant/, /stress or distress/ and /BMI, body mass index or overweight or obesity or body composition/. Results: The results of the research were inconsistent. Nevertheless, most articles confirmed the positive association of prenatal stress with fatness indicators in children. The review raised a question of the role of the methods applied for stress measurement (objective vs. subjective indicators) and adiposity assessment, as well as the time of prenatal exposition to stress. Conclusion: Most studies have proved that prenatal stress is related to the children adiposity in postnatal life.

REVIEW ON THE IMPACT AND CONSEQUENCES OF THE OCCURRENCE OF MULTIPLE BIRTHS IN CATTLE AND GOATS

Background: The large animal species such as cattle, buffaloes and horses are monotocous with one or sometimes two newborns per birth whereas small farm animal species such as sheep, goats and pigs are usually polytocous animals are highly prolific and especially pigs often produce a dozen newborns at each farrowing. Cattle usually produce only one calf per gestation resulting from ovulation of a single follicle. The most common form of twinning in cattle occurs due to multiple ovulations which may produce dizygotic twins. The twin births in dairy cattle often negatively impacts the reproduction, production, health and reduces the productive lifespan of cows. Therefore, there is a great interest to know the multiple ovulations and multiple births to reduce the twinning rate in dairy cattle herds. Objective: This review updates the status of multiple births and its impact and consequences on production of dairy cattle and goats. Materials and Methods: The related literatures on the multiple births in cattle and goats have been reviewed for which the search was carried out in Google Scholar, PubMed, CrossRef, Banglajol and also the online daily newspapers. Results: Although multiple births with up to quadruplets have been reported from different countries, the prevalence of twin births are commonly reported in dairy cattle. The prevalence of twinning rates are varied widely in different breeds like twin calving in Holstein Friesian cattle is 3 to 5%, 5.6% Spanish dairy herd and 3.9% in Iranian Holsteins, whereas triplet and quadruplet births represent 0.015% and 0.004% of the total births, respectively. Twin calving shorten gestation length, increased dystocia, stillbirths, decrease birth weight, perinatal calf mortality, retained placenta, decrease milk production, increases the occurrence of metabolic diseases, reduced conception rate, increased calving interval, shorten the productive lifespan of the dam and increases overall culling rate. Two strategies- the transfer of a single embryo produced in vitro and follicular drainage of co-dominant follicles at AI have been suggested to prevent twin pregnancies. Conclusion: Multiple births in dairy cattle is not desirable due to negative effects on both cows that calve twins and calves born as twins that result in economic losses in dairy herds. Regardless of the direct effect of multiple births on health and fertility, reducing the occurrence of multiple ovulations to decrease the risk of twin births is desirable to mitigate the negative consequences of twinning in dairy cattle. The estimated losses due to twinning range between US$ 59 to 161 per twin pregnancy and attempting manual embryo reduction decreased the economic losses of a twin pregnancy by US $ 23 to 45. Bangladesh scientists discovered a new technique to produce twin calves but the future research on this aspect need to consider the negative effects of twin births in cattle.

Socio-anthropometric features and lifestyle in ketosis-prone diabetes vs controls

: In West Africa, the various types of diabetes according to WHO or the American Diabetes Association (ADA) are endemic; however, a particular type referred to as atypical ketosis-prone diabetes mellitus requires specific attention. We implemented a case-control study including 101 cases versus 89 controls. Controls are people living in apparent good health and patients are diabetics newly diagnosed and attended hospitals for the first time. We included socio-demographic and anthropometric informations, some questions about dietary habits of participants. We tested fasting plasma glucose and HbAC according to manufacturer’s instructions. : Dietary diversification was lower in patients with less of 10% having a good dietary diversity. Correlation tests showed a significant statistical link in relation with waist circumference and body mass index in accordance with glycaemia in patients newly diagnosed diabetics. Wenoted adecreasing of mean value of glycaemia in overweight or obese patients, otherwise, the fat gaining was marked as glycaemia lowering. This trend has been related in correlation with HbA1C in patients without significant statistical correlation. We also notified a significant link between amount of diet usually ingested by controls and the variation of HbA1C. : It clearly appears that lifestyle has certainly an impact in the occurrence of metabolic diseases in overall and on diabetes in particular. There is a close link between these diseases with genetic or family predisposition. It seems urgent to act upstream to prevent such diseases living as a burden for our deprived population.

REVIEW ON THE IMPACT AND CONSEQUENCES OF THE OCCURRENCE OF MULTIPLE BIRTHS IN CATTLE AND GOATS

Background: The large animal species such as cattle, buffaloes and horses are monotocous with one or sometimes two newborns per birth whereas small farm animal species such as sheep, goats and pigs are usually polytocous animals are highly prolific and especially pigs often produce a dozen newborns at each farrowing. Cattle usually produce only one calf per gestation resulting from ovulation of a single follicle. The most common form of twinning in cattle occurs due to multiple ovulations which may produce dizygotic twins. The twin births in dairy cattle often negatively impacts the reproduction, production, health and reduces the productive lifespan of cows. Therefore, there is a great interest to know the multiple ovulations and multiple births to reduce the twinning rate in dairy cattle herds. Objective: This review updates the status of multiple births and its impact and consequences on production of dairy cattle and goats. Materials and Methods: The related literatures on the multiple births in cattle and goats have been reviewed for which the search was carried out in Google Scholar, PubMed, CrossRef, Banglajol and also the online daily newspapers. Results: Although multiple births with up to quadruplets have been reported from different countries, the prevalence of twin births are commonly reported in dairy cattle. The prevalence of twinning rates are varied widely in different breeds like twin calving in Holstein Friesian cattle is 3 to 5%, 5.6% Spanish dairy herd and 3.9% in Iranian Holsteins, whereas triplet and quadruplet births represent 0.015% and 0.004% of the total births, respectively. Twin calving shorten gestation length, increased dystocia, stillbirths, decrease birth weight, perinatal calf mortality, retained placenta, decrease milk production, increases the occurrence of metabolic diseases, reduced conception rate, increased calving interval, shorten the productive lifespan of the dam and increases overall culling rate. Two strategies- the transfer of a single embryo produced in vitro and follicular drainage of co-dominant follicles at AI have been suggested to prevent twin pregnancies. Conclusion: Multiple births in dairy cattle is not desirable due to negative effects on both cows that calve twins and calves born as twins that result in economic losses in dairy herds. Regardless of the direct effect of multiple births on health and fertility, reducing the occurrence of multiple ovulations to decrease the risk of twin births is desirable to mitigate the negative consequences of twinning in dairy cattle. The estimated losses due to twinning range between US$ 59 to 161 per twin pregnancy and attempting manual embryo reduction decreased the economic losses of a twin pregnancy by US $ 23 to 45. Bangladesh scientists discovered a new technique to produce twin calves but the future research on this aspect need to consider the negative effects of twin births in cattle.

Mechanistic Target of Rapamycin Complex 1: From a Nutrient Sensor to a Key Regulator of Metabolism and Health.

Mechanistic target of rapamycin complex 1 (mTORC1) is a multi-protein complex widely found in eukaryotes. It serves as a central signaling node to coordinate cell growth and metabolism by sensing diverse extracellular and intracellular inputs, including amino acid-, growth factor-, glucose-, and nucleotide-related signals. It is well documented that mTORC1 is recruited to the lysosomal surface, where it is activated and, accordingly, modulates downstream effectors involved in regulating protein, lipid, and glucose metabolism. mTORC1 is thus the central node for coordinating the storage and mobilization of nutrients and energy across various tissues. However, emerging evidence indicated that the overactivation of mTORC1 induced by nutritional disorders leads to the occurrence of a variety of metabolic diseases, including obesity and type 2 diabetes, as well as cancer, neurodegenerative disorders, and aging. That the mTORC1 pathway plays a crucial role in regulating the occurrence of metabolic diseases renders it a prime target for the development of effective therapeutic strategies. Here, we focus on recent advances in our understanding of the regulatory mechanisms underlying how mTORC1 integrates metabolic inputs as well as the role of mTORC1 in the regulation of nutritional and metabolic diseases.

Early metabolic profiling in the periparturient period reduces the occurrence of postparturient metabolic diseases in cows.

Objective:To study the impact of early metabolic profiling and intervention measures in the periparturient period on the occurrence of postparturient metabolic diseases in cows.Materials and Methods:Using a cohort of dairy cows from two selected areas of Bangladesh, we routinely tested the serum calcium level and ketone bodies in the urine at periparturient periods. In addition, milk samples were tested for the presence of mastitis at different stages of lactation. Animals showing reduced serum calcium levels, high ketone bodies in the urine or the presence of clinical and subclinical mastitis received appropriate therapeutic intervention immediately after detection. After the intervention, the number of animals that got sick with diseases or conditions like milk fever, ketosis, mastitis, and dystocia, which are caused by metabolic problems, was recorded.Results:In the periparturient period, most of the animals had lower serum calcium levels (8.13 ± 1.2 mg/dl), which were significantly increased by the following intervention (10.05 ± 1.4 mg/dl). On the other hand, there was a higher number of ketosis-affected animals (33.9%, 20/59) during the periparturient period, which decreased (18.6%, 11/59) during the postparturient period. Similarly, the number of mastitis-affected cows was also decreased in postparturient cows (30.9%, 13/42) than in periparturient cows (59.5%, 25/42), following improved hygienic measures. After early intervention, the number of study animals with metabolic diseases decreased from 51.7% before intervention to 15.3% after intervention.Conclusions:Early metabolic profiling significantly reduced the occurrence of metabolic diseases in cows. Therefore, we recommend regular metabolic profiling of dairy cows and receiving early intervention measures to reduce the occurrence of metabolic diseases on the farm.

Zinc Supplementation Improved Neuropeptide Y, Nesfatin-1, Leptin, C-reactive protein, and HOMA-IR of Diet-Induced Obese Rats.

Obesity is a mild chronic inflammation that causes many metabolic diseases. It was aimed to investigate some parameters affective on the energy metabolism by adding zinc (Zn, ZnSO4) to drinking water of diet-induced obese rats. Five-week aged, male Sprague Dawley rats divided into as control group, consuming standard rat diet, and high-fat diet (HFD) group. After obesity induced by feeding HFD for 8weeks, the obese rats were divided into Zn-supplemented obese group (HFD + obese + Zn; 150mg Zn/L (for 6weeks), 235mg Zn/L (7th week), 250mg Zn/L (8th week) in drinking water) and obese group (HFD + obese).Mean body weight, serum concentrations of C-reactive protein, neuropeptide-Y, leptin, insulin fasting blood glucose, and HOMA-IR were statistically decreased by given Zn in HFD + obese + Zn group compared to HFD + obese rats. It was observed that the total cholesterol, LDL, and HDL cholesterol levels of HFD + obese + Zn group became closer to the control group level, and Zn supplementation caused a statistically significant decrease in cholesterol profile than HFD + obese rats. Also, increased mean serum nesfatin-1 level, an effective protein for the formation of satiety, was analyzed in HFD + obese + Zn group when compared to HFD + obese ones. Serum triglyceride concentration tended to decrease with the effect of Zn in obese rats. In conclusion, it can be said that oral use of Zn could improve energy balance and prevent the occurrence of metabolic diseases related to obesity depending on the anti-inflammatory effect of Zn.

Metabolic diseases in cattle

The main trend in the development of dairy farming in the Russian Federation suggests maximising milk yield and reducing milk net cost. The economic effectiveness of industrial dairy farming is largely determined by adequate feeding, as well as effective system of measures to ensure animal health and prevent infectious and non-infectious mass diseases. The main reason for the premature retirement of highly productive cows is based on the factors typical of the intensive technologies used in dairy cattle breeding, which lead to the occurrence of metabolic diseases. It is established that the intensity of metabolism is directly linked to the high productivity of cows. With a highly concentrated, mainly silage-based type of feeding, an imbalance of nutrients is often recorded, in particular as regards the sugar/ protein ratio, leading to deep metabolic disorders and the development of immunodeficiency states. Metabolic disorders in highly productive cows occur as a result of unbalanced diets as far as protein, carbohydrates, vitamins and minerals are concerned. Acidosis, ruminitis and hepatosis are recorded in disordered cows and heifers. The service period exceeds 100 days in 70–75% of cows. Hepatosis and immunodeficiency states are often found in calves born to cows with signs of deep metabolic disorders. Metabolic disorders often remain unnoticed and become apparent only when pronounced pathological changes occur resulting in decreased productivity and ability to reproduce resistant young animals, as well as culling of animals. Metabolic diseases were recorded in 30–70% of cows examined in large dairy farms. The average lifetime productivity of high-yielding cows is (2.1 ± 0.15) lactations in Russia. The results of epidemiological investigations and laboratory testing of sera samples showed that emulsion inactivated vaccines administered to immunodeficient cattle induce higher titres of virus-specific antibodies than those in animals vaccinated with adsorbed vaccines.

Influence of different levels of dietary protein on serum biochemical parameters of dairy cows during the transition period

A study was carried out to find the influence of different dietary protein levels on serum biochemical parameters of dairy cows during the transition period. Twenty cross bred cows, three weeks prior to their expected date of calving were selected from University Livestock Farm and Fodder Research and Development Scheme (ULF&amp;FRDS), College of Veterinary and Animal Sciences, Mannuthy as experimental animals. The cows were randomly allotted to two dietary treatments – T1 (12 per cent CP (crude protein) TMR (Total Mixed Ration)) and T2 (14 per cent CP TMR). After calving, half of the animals in T1 were allotted to T3 (16 per cent CP TMR) and remaining half to T4 (18 per cent CP TMR). Similarly half of the animals in T2 were allotted to T3 and remaining half to T4. All these rations were iso-caloric. The feeding trial was carried out for a period of 3 weeks prepartum and 45 days postpartum. The serum biochemical parameters such as serum glucose levels were significantly higher (p&lt;0.05) for groups receiving treatments T2 &amp; T4 (84.87±2.64 mg/dL) and total protein levels were significantly lower for groups receiving treatments T1 and T3and the levels of all other biochemical parameters under observation remained unaffected in all treatment combinations, but the values of NEFA (non-esterified fatty acids) were below the normal range. Furthermore, there was no occurrence of metabolic diseases in any of the treatment groups, indicating that dietary treatments were sufficient to meet the requirement of the animals. Dietary protein levels did not have any significant effect on serum metabolites studied in the present work.

Occurrence of metabolic diseases associated with antipsychotic use among Korean patients with schizophrenia.

Metabolic side effects of antipsychotics significantly affect adherence to medication. We aimed to identify factors associated with the occurrence of metabolic diseases among Korean patients with schizophrenia (SCZ) from the national health insurance system database. We evaluated the frequency of antidiabetic and antihyperlipidemic use after diagnosis of SCZ according to typical or atypical antipsychotic use. Among the 43,800 patients diagnosed with SCZ between 2008 and 2012, 29,591 patients who had no metabolic diseases before the diagnosis were included in the analysis to investigate the occurrence of metabolic diseases associated with antipsychotic use. The associations between the development of metabolic diseases and patient characteristics were evaluated using logistic regression analysis. Use of both typical and atypical antipsychotics (multivariate-adjusted odds ratio (OR), 1.2513; 95% confidence interval (CI), 1.0953-1.4294) was associated with higher incidence of metabolic diseases than without their use. Among the atypical antipsychotics, use of clozapine (multivariate-adjusted OR, 1.1959; 95% CI, 1.0086-1.4179) and quetiapine (multivariate-adjusted OR, 1.1284; 95% CI, 1.0446-1.2189) showed higher incidence of metabolic diseases compared to that without their use. Among the patients using ≥1 type of antidiabetic or antihyperlipidemic agents within 6years after diagnosis of SCZ, the proportion of patients using only atypical antipsychotics was greater than those using only typical antipsychotics. The use of both typical and atypical antipsychotics, and clozapine and quetiapine treatment, may be associated with the occurrence of metabolic diseases in patients with SCZ. Additional prospective studies with accurate dosage information are needed to validate our findings.

Improvements in estrogen deficiency-induced hypercholesterolemia by Hypericum perforatum L. extract are associated with gut microbiota and related metabolites in ovariectomized (OVX) rats

Hypericum perforatum L. (HP), a well-known natural medicine, has a potential effect on menopausal hypercholesterolemia. However, the effect of HP extract on gut microbiota and related metabolites, which play vital roles in metabolic disease occurrence, in the context of estrogen deficiency have not yet been reported. The aims of the present study were to investigate the effects of HP extract on gut microbial composition and related metabolite profiles in ovariectomized (OVX) rats and reveal the relationships between pathological indicators and alterations in both gut microbial composition at the genus level and metabolites. Body weight, serum parameters, liver lipids and histomorphology were determined. Microbial composition was analyzed using 16S rRNA sequencing. Fecal short-chain fatty acids (SCFAs) and serum bile acids were quantitatively measured. Correlations between pathological indicators and alteration in gut microbiota and metabolites were investigated using Spearman's rank correlation test. Gene expression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7α-hydroxylase (CYP7A1) and cholesterol 27-hydroxylase (CYP27A1) in the liver and G protein-coupled receptors (GPCRs; GPR43 and GPR41), ZO-1 and occludin in the cecum were determined by PCR. Microbial composition and metabolite profiles were significantly changed in OVX rats compared with sham rats. Twelve bacterial genera, 5 SCFAs and 12 bile acids were identified as differential biomarkers. Differential genera, SCFAs and bile acids were closely associated with weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In OVX rats, HP administration can significantly reverse the pathological symptoms of body weight gain, serum lipid disorders and hepatic steatosis, at the meanwhile, reestablish gut microbial composition and metabolite profiles. Moreover, HP administration significantly upregulated the levels of CYP7A1, GPR43 and GPR41. In conclusion, HP can ameliorate estrogen deficiency-induced hypercholesterolemia. The underlying mechanism may be associated with improvements in gut microbiota composition and the profile of related metabolites as well as increases in bile acid secretion.

Integrated transcriptome and phosphoproteome analyses reveal that fads2 is critical for maintaining body LC-PUFA homeostasis

Fatty acid desaturate 2 (Fads2) is associated with many chronic diseases. Nevertheless, comprehensive researches on its role have not been performed. We here conducted an integrated analysis of long-chain polyunsaturated fatty acid (LC-PUFA) metabolism of fads2-deletion zebrafish (fads2−/−) by transcriptomics, proteomics and phosphoproteomics. Compared with wild type zebrafish (WT), fads2−/− showed significantly higher contents of hepatic linoleic acid (all-cis-9,12-C18:2), α-linolenic acid (all-cis-9,12,15-C18:3) and docosapetaenoic acid (all-cis-7,10,13,16,19-C22:5), and lower contents of γ-linolenic acid (all-cis-6,9,12-C18:3), stearidonic acid (all-cis-6,9,12,15-C18:4) and docosahexaenoic acid (all-cis-4,7,10,13,16,19-C22:6), accompanied by an increased n-6/n-3 PUFA level. In total, we identified 1608 differentially expressed genes (DEGs), 209 differentially expressed proteins (DEPs) and 153 differentially expressed phosphorylated proteins (DEPPs) with 190 sites between fads2−/− and WT. Transcriptome and proteome analysis simultaneously aggregated these DEGs and DEPs into LC-PUFA synthesis and PPAR signaling pathways. Further interaction network analysis of the DEPPs showed that spliceosome and protein processing in endoplasmic reticulum pathway were critical groups. Additionally, we determined seven highly phosphorylated kinases and a highly expressed phosphatase in fads2−/− zebrafish. These results give insights into the mechanism by which fads2 affects metabolic disease occurrence, and provide datasets for target selections for human disease treatment. SignificanceBalanced LC-PUFA composition was deeply associated with body health, while changes of LC-PUFAs usually induced serious diseases such as cardiovascular disease, type 2 diabetes and inflammatory disease. Fatty acid desaturase 2 (Fads2), subordinating to the fatty acid desaturase protein family, catalyzes the first desaturation reaction in LC-PUFA synthesis. Although Fads2 is associated with many chronic diseases including metabolic abnormalities, type 2 diabetes and obesity, comprehensive researches on its role have not been performed.On the basis of the integrated transcriptome, proteome and phosphoproteome analysis, we identified that fads2 was critical for maintaining body LC-PUFA homeostasis. Moreover, the crucial pathways including PPAR signaling pathway, spliceosome and protein processing in endoplasmic reticulum pathway, and candidate kinase targets associated with LC-PUFA metabolism were determined. These findings will contribute to the revealing of the mechanism and supply possible datasets for target selection for human disease treatment.

Revisiting the Bacterial Phylum Composition in Metabolic Diseases Focused on Host Energy Metabolism.

Over a hundred billion bacteria are found in human intestines. This has emerged as an environmental factor in metabolic diseases, such as obesity and related diseases. The majority of these bacteria belong to two dominant phyla, Bacteroidetes and Firmicutes. Since the ratio of Firmicutes to Bacteroidetes increases in people with obesity and in various animal models, it has been assumed that phylum composition causes the increase in occurrence of metabolic diseases over the past decade. However, this assumption has been challenged by recent studies that have found even an opposite association of phylum composition within metabolic diseases. Moreover, the gut microbiota affects host energy metabolism in various ways including production of metabolites and interaction with host intestinal cells to regulate signaling pathways that affect energy metabolism. However, the direct effect of gut bacteria on host energy intake, such as energy consumption by the bacteria itself and its effects on intestinal energy absorption, has been underestimated. This review aims to discuss whether increased ratio of Firmicutes to Bacteroidetes is associated with the development of metabolic diseases, and whether energy competition between the bacteria and host is a missing part of the mechanism linking gut microbiota to metabolic diseases.