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Abstract Background Glucose metabolic disorder is associated with the risk of heart failure (HF). Adiposity is a comorbidity that is inextricably linked with abnormal glucose metabolism in older individuals. However, the effect of adiposity on the association between glucose metabolic disorder and HF risk, and the underlying mechanism remain unclear. Methods A total of 13,251 participants aged ≥ 60 years from a cohort study were categorized into euglycemia, prediabetes, uncontrolled diabetes, and well-controlled diabetes. Adiposity was assessed using body mass index (BMI), waist-to-hip ratio (WHR), and visceral fat area (VFA). Adiposity-associated metabolic activities were evaluated using adiponectin-to-leptin ratio (ALR), homeostatic model assessment of insulin resistance (HOMA-IR), and triglyceride-glucose index (TyG). The first occurrence of HF served as the outcome during the follow-up period. Results A total of 1,138 participants developed HF over the course of an average follow-up period of 10.9 years. The rate of incident HF occurrence was higher in prediabetes, uncontrolled diabetes, and well-controlled diabetes participants compared to that in euglycemia participants. However, the high rates were significantly attenuated by BMI, VFA, and WHR. For WHR in particular, the hazard ratio for incident HF was 1.18 (95% confidence interval (CI): 1.03, 1.35, P adj. =0.017) in prediabetes, 1.59 (95% CI: 1.34, 1.90, P adj.

Abstract Background Eurasian pigs have undergone lineage admixture throughout history. It has been confirmed that the genes of indigenous pig breeds in China have been introduced into Western commercial pigs, providing genetic materials for breeding Western pigs. Pigs in Taihu Lake region (TL), such as the Meishan pig and Erhualian pig, serve as typical representatives of indigenous pig breeds in China due to their high reproductive performances. These pigs have also been imported into European countries in 1970 and 1980 s. They have played a positive role in improving the reproductive performances in European commercial pigs such as French Large White pigs (FLW). However, it is currently unclear if the lineage of TL pigs have been introgressed into the Danish Large White pigs (DLW), which are also known for their high reproductive performances in European pigs. To systematically identify genomic regions in which TL pigs have introgressed into DLW pigs and their physiological functions, we collected the re-sequencing data from 304 Eurasian pigs, to identify shared haplotypes between DLW and TL pigs. Results The findings revealed the presence of introgressed genomic regions from TL pigs in the genome of DLW pigs indeed. The genes annotated within these regions were found to be mainly enriched in neurodevelopmental pathways. Furthermore, we found that the 115 kb region located in SSC16 exhibited highly shared haplotypes between TL and DLW pigs. The major haplotype of TL pigs in this region could significantly improve reproductive performances in various pig populations. Around this genomic region, NDUFS4 gene was highly expressed and showed differential expression in multiple reproductive tissues between extremely high and low farrowing Erhualian pigs. This suggested that NDUFS4 gene could be an important candidate causal gene responsible for affecting the reproductive performances of DLW pigs. Conclusions Our study has furthered our knowledge of the pattern of introgression from TL into DLW pigs and the potential effects on the fertility of DLW pigs.

Introduction: Intramuscular fat content (IFC) and meat color are vital indicators of pork quality.Methods: A significant positive correlation between IFC and redness of meat color (CIE a* value) indicates that these two traits are likely to be regulated by shared molecular pathways.To identify candidate genes, hub genes, and signaling pathways that regulate these two traits, we measured the IFC and CIE a* value in 147 hybrid pigs, and selected individuls with extreme phenotypes for transcriptome analysis.Results: The results revealed 485 and 394 overlapping differentially expressed genes (DEGs), using the DESeq2, limma, and edgeR packages, affecting the IFC and CIE a* value, respectively. Weighted gene co-expression network analysis (WGCNA) identified four modules significantly correlated with the IFC and CIE a* value. Moreover, we integrated functional enrichment analysis results based on DEGs, GSEA, and WGCNA conditions to identify candidate genes, and identified 47 and 53 candidate genes affecting the IFC and CIE a* value, respectively. The protein protein interaction (PPI) network analysis of candidate genes showed that 5 and 13 hub genes affect the IFC and CIE a* value, respectively. These genes mainly participate in various pathways related to lipid metabolism and redox reactions. Notably, four crucial hub genes (MYC, SOX9, CEBPB, and PPAGRC1A) were shared for these two traits.Discussion and conclusion: After functional annotation of these four hub genes, we hypothesized that the SOX9/CEBPB/PPARGC1A axis could co-regulate lipid metabolism and the myoglobin redox response. Further research on these hub genes, especially the SOX9/CEBPB/PPARGC1A axis, will help to understand the molecular mechanism of the co-regulation of the IFC and CIE a* value, which will provide a theoretical basis for improving pork quality.

Muscle satellite cells (MuSCs) are crucial for muscle development and regeneration. The primary pig MuSCs (pMuSCs) is an ideal in vitro cell model for studying the pig’s muscle development and differentiation. However, the long-term in vitro culture of pMuSCs results in the gradual loss of their stemness, thereby limiting their application. To address this conundrum and maintain the normal function of pMuSCs during in vitro passaging, we generated an immortalized pMuSCs (SV40 T-pMuSCs) by stably expressing SV40 T-antigen (SV40 T) using a lentiviral-based vector system. The SV40 T-pMuSCs can be stably sub-cultured for over 40 generations in vitro. An evaluation of SV40 T-pMuSCs was conducted through immunofluorescence staining, quantitative real-time PCR, EdU assay, and SA-β-gal activity. Their proliferation capacity was similar to that of primary pMuSCs at passage 1, and while their differentiation potential was slightly decreased. SiRNA-mediated interference of SV40 T-antigen expression restored the differentiation capability of SV40 T-pMuSCs. Taken together, our results provide a valuable tool for studying pig skeletal muscle development and differentiation.

Background The impacts and mechanisms of morning hypertension (MHT) on the risk of new-onset atrial fibrillation (AF) in the elderly have not been clarified. We aimed to investigate an association between MHT and new-onset AF and explore a mediating effect of subclinical inflammation on this association. Methods From 2008 to 2010, 1789 older adults aged ≥60 years were recruited in Shandong area, China. Morning blood pressure (BP) was assessed using 24-hour ambulatory BP monitoring. MHT was defined as BP ≥ 135/85 mm Hg during the period from wake time to 0900 a.m. Subclinical inflammation was assessed by hypersensitive C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and galectin-3. New-onset AF was rated during the follow-up period. Results Over an average 129.0 [standard deviation (SD): 21.58] months of follow-up, the hazard ratio of new-onset AF in MHT patients was 1.39 (95% confidence interval: 1.01 to 1.91) compared with non-MHT participants (Padjusted = 0.027). The risk of new-onset AF was 1.17-fold with one-SD increment of morning systolic BP. Subclinical inflammation was significantly associated with new-onset AF. The hazard ratios of new-onset AF were 2.29, 2.04, 2.08, 2.08, 2.03, and 3.25 for one-SD increment in hsCRP, TNF-α, SII, NLR, PLR, and galectin-3, respectively (Padjusted < 0.001). The analysis showed that hsCRP, TNF-α, SII, NLR, PLR, and galectin-3 separately mediated the process of MHT inducing new-onset AF (Padjusted < 0.05). Conclusions MHT is associated with an increased risk of new-onset AF. The subclinical inflammation might play a mediating role in this association.

The introduction of single-cell RNA sequencing (scRNA-seq) technology has spurred additional advancements in analyzing the cellular composition of tissues. The longissimus dorsi (LD) in pigs serves as the primary skeletal muscle for studying meat quality in the pig industry. However, the single-cell profile of porcine LD is still in its infancy stage. In this study, we profiled the transcriptomes of 16,018 cells in the LD of a newborn Suhuai pig at single-cell resolution. Subsequently, we constructed a cellular atlas of the LD, identifying 11 distinct cell populations, including endothelial cells (24.39%), myotubes (18.82%), fibro-adipogenic progenitors (FAPs, 18.11%), satellite cells (16.74%), myoblasts (3.99%), myocytes (5.74%), Schwann cells (3.81%), smooth muscle cells (3.22%), dendritic cells (2.99%), pericytes (1.86%), and neutrophils (0.33%). CellChat was employed to deduce the cell–cell interactions by evaluating the gene expression of receptor–ligand pairs across different cell types. The results show that FAPs and pericytes are the primary signal contributors in LD. In addition, we delineated the developmental trajectory of myogenic cells and examined alterations in the expression of various marker genes and molecular events throughout various stages of differentiation. Moreover, we found that FAPs can be divided into three subclusters (NR2F2-FAPs, LPL-FAPs, and TNMD-FAPs) according to their biological functions, suggesting that the FAPs could be associated with the differentiation of tendon cell. Taken together, we constructed the cellular atlas and cell communication network in LD of a newborn Suhuai pig, and analyzed the developmental trajectory of myogenic cells and the heterogeneity of FAPs subpopulation cells. This enhances our comprehension of the molecular features involved in skeletal muscle development and the meat quality control in pigs.

Abstract Integrating the single‐nucleotide polymorphisms (SNPs) significantly affecting target traits from imputed whole‐genome sequencing (iWGS) data into the genomic prediction (GP) model is an economic, efficient, and feasible strategy to improve prediction accuracy. The objective was to dissect the genetic architecture of intramuscular fat content (IFC) by genome wide association studies (GWAS) and to investigate the accuracy of GP based on pedigree‐based BLUP (PBLUP) model, genomic best linear unbiased prediction (GBLUP) models and Bayesian mixture (BayesMix) models under different strategies. A total of 482 Suhuai pigs were genotyped using an 80 K SNP chip. Furthermore, 30 key samples were selected for resequencing and were used as a reference panel to impute the 80 K chip data to the WGS dataset. The 80 K data and iWGS data were used to perform GWAS and test GP accuracies under different scenarios. GWAS results revealed that there were four major regions affecting IFC. Two important functional candidate genes were found in the two most significant regions, including protein kinase C epsilon (PRKCE) and myosin light chain 2 (MYL2). The results of the predictions showed that the PBLUP model had the lowest reliability (0.096 ± 0.032). The reliability (0.229 ± 0.035) was improved by replacing pedigree information with 80 K chip data. Compared with using 80 K SNPs alone, pruning iWGS SNPs with the R‐squared cutoff of linkage disequilibrium (0.55) led to a slight improvement (0.006), adding significant iWGS SNPs led to an improvement of reliability by 0.050 when using a one‐component GBLUP, a further increase of 0.033 when using a two‐component GBLUP model. For BayesMix models, compared with using 80 K SNPs alone, adding additional significant iWGS SNPs into one‐ or two‐component BayesMix models led to improvements of reliabilities for IFC by 0.040 and 0.089, respectively. Our results may facilitate further identification of causal genes for IFC and may be beneficial for the improvement of IFC in pig breeding programs.

Abstract Background Due to the high nursing pressure of patients with cerebral hemorrhage and the general shortage of clinical nurses, nursing support workers often participate in clinical nursing work, but the influence of nursing support workers' participation on the negative emotion, quality of life and life satisfaction of patients with intracerebral hemorrhage is unknown. Methods This quasi-experimental study was conducted with a pretest–posttest design. A total of 181 ICH patients admitted to our hospital from January 2022 to April 2022 were enrolled, including 81 patients receiving conventional care (CG control group) and 80 patients receiving nursing support worker participation (RG research group). All patients were recorded with self-perceived Burden Scale (SPBS), Hamilton Depression Scale (HAMD), Quality of Life Scale (SF-36), Somatic Self rating Scale (SSS), Patient self-care ability assessment scale (Barthel) and Satisfaction with life scale (SWLS) scores. Results Patients with high negative emotion were more willing to participate in clinical nursing work (p

Non-small cell lung cancer (NSCLC) is one of the most serious diseases affecting human health today, and current research is focusing on gut flora. There is a correlation between intestinal flora imbalance and lung cancer, but the specific mechanism is not clear. Based on the “lung and large intestine being interior-exteriorly related” and the “lung-intestinal axis” theory. Here, based on the theoretical comparisons of Chinese and western medicine, we summarized the regulation of intestinal flora in NSCLC by active ingredients of traditional Chinese medicine and Chinese herbal compounds and their intervention effects, which is conducive to providing new strategies and ideas for clinical prevention and treatment of NSCLC.

To evaluate the tolerance of a high-fiber diet in Erhualian pigs (Er-HL), the present investigation systematically investigated the ramifications of varying wheat bran fiber levels, specified as total dietary fiber (TDF) values of 14.07%, 16.32%, 17.99%, and 18.85%, on growth performance, fiber digestibility and gut microbiota in Er-HL, large Large White pigs (L-LW, the same physiological stage as the Er-HL) and small Large White pigs (S-LW, the same body weight as the Er-HL). Our results revealed that fiber levels exerted no discernable impact on growth performance (average daily feed intake (ADFI), and average daily gain (ADG)) of Er-HL (p > 0.05). Conversely, L-LW exhibited a decrease in ADFI and ADG with increasing fiber levels (p < 0.05). Notably, the apparent total tract digestibility (ATTD) of various fiber components, including neutral detergent fiber (NDF), acid detergent fiber (ADF), hemicellulose, TDF and insoluble dietary fiber (IDF), in Er-HL were significantly higher than those in S-LW and L-LW irrespective of diets (p < 0.05). The ATTD of cellulose and hemicellulose in Er-HL significantly decreased with increasing fiber levels (p < 0.05), yet remained statistically indifferent when comparing the 7%-wheat-bran-replaced diet (7% WRB, TDF 16.32%) to the basal diet (TDF 14.07%) (p > 0.05). The cecal microbiota of Er-HL had higher richness estimators (Chao1 and ACE) than those of S-LW and L-LW irrespective of diets (p < 0.01). Breed serves as a pivotal determinant in shaping swine gut microbiota. Thirteen genera were selected as the key bacteria related to high fiber digestibility of Er-HL. Further functional examination of these key genera elucidated an enrichment of pathways pertinent to carbohydrate metabolism in Er-HL samples compared with S-LW and L-LW samples. In summary, Er-HL exhibited high-fiber tolerance both in terms of growth performance and fiber digestibility compared with Large White pigs. Specifically, the ATTD of NDF, ADF, hemicellulose, IDF and TDF were significantly higher in Er-HL compared with L-LW and S-LW, irrespective of diets. Fiber level exerted no discernable impact on growth performance (ADFI, ADG) and the ATTD of fiber (NDF, ADF, IDF and TDF) in Er-HL. The optimum fiber level of the Er-HL was identified as 7% WRB (TDF 16.32%). Thirteen genera were ascertained to significantly contribute to high fiber digestibility of Er-HL, correlating with an enhancement of carbohydrate metabolism pathways.

ABSTRACT Previous study found that appropriate high-fiber diet (containing 19.10% total dietary fiber [TDF], treatment II) did not reduce apparent fiber digestibility of Chinese Suhuai finishing pigs and increased the yield of short-chain fatty acids (SCFAs), but too high-fiber diet (containing 24.11% TDF, treatment IV) significantly reduced apparent fiber digestibility compared with normal diet (containing 16.70% TDF, control group). However, characteristics of microbiota at the species level and histological structure in pigs with the ability to digest appropriate high-fiber diets were still unknown. This study conducted comparative analysis of cecal physiology and microbial populations colonizing cecal mucosa. The results showed intestinal development indexes including cecum length, densities of cecal goblet cells, and renewal of cecal epithelial cells in treatment II and IV had better performance than those in the control. Paludibacter jiangxiensis, Coprobacter fastidiosus, Bacteroides coprocola CAG:162, Bacteroides barnesiae, and Parabacteroides merdae enriched in treatment II expressed large number of glycoside hydrolase (GH)-encoding genes and had the largest number of GH families. In addition, pathogenic bacteria (Shigella sonnei, Mannheimia haemolytica, and Helicobacter felis) were enriched in treatment IV. Correlation analysis revealed that the intestinal development index positively correlated with the relative abundance of cecal mucosal microbiota and the amount of digested fiber. These results indicated that increased proportions of fiber-degrading microbes and enhanced intestinal development jointly promote the host to digest an appropriate high-fiber diet. However, although too-high fiber levels in diet could maintain the adaptive development of cecal epithelium, the proportions of pathogenic bacteria increased, which might lead to a decrease of fiber digestion in pigs. IMPORTANCE Although studies about the effects of dietary fiber on fiber digestion and intestinal microbiota of pigs were widely in progress, few studies have been conducted on the dynamic response of intestinal microbiota to dietary fiber levels, and the characteristics of intestinal microbiota and intestinal epithelial development adapted to high-fiber diet s were still unclear. Appropriate high fiber promoted the thickness of large intestine wall, increased the density of cecal goblet cells, and promoted the renewal of cecal epithelial cells. In addition, appropriate high fiber improves the microbial abundance with fiber-digesting potential. However, excessive dietary fiber caused an increase in the abundance of pathogenic bacteria. These results indicated that an increased proportion of fiber-degrading microbes and enhanced intestinal development jointly promote host to digest appropriate high-fiber diets. However, although too-high fiber levels in diet could maintain the adaptive development of cecal epithelium, the proportions of pathogenic bacteria increased, which might lead to a decrease of fiber digestion in pigs. Our data provided a theoretical basis for rational and efficient utilization of unconventional feed resources in pig production.

MicroRNAs (miRNAs) are posttranscriptional regulators that play key roles in meat color regulation. Changes in miRNA expression affect their target mRNAs, leading to multifunctional effects on biological processes and phenotypes. In this study, a G > A mutation site located upstream of the precursor miR-22 sequence in Suhuai pigs was significantly correlated with the meat color parameter a*(redness) of the porcine longissimus dorsi (LD) muscle. AA genotype individuals had the highest average meat color a* value and the lowest miR-22 level. When G > A mutation was performed in the miR-22 overexpression vector, miR-22 expression significantly decreased. Considering that Ca2+ homeostasis is closely related to pig meat color, our results further demonstrated that ELOVL6 is a direct target of miR-22 in pigs. The effects of miR-22 on skeletal muscle intracellular Ca2+ were partially caused by the suppression of ELOVL6 expression.

Finishing pigs can adapt to high-fiber diet smoothly according to the production performance and their intestinal microbiota through a 28-day trial or longer. However, it is unclear, at which stage during the experimental period, the adaptation occurred. Here we studied the dosage effects of dietary fiber (Total dietary fiber (TDF) from 16.70 to 24.11%) on growth performance, fiber digestibility, fecal microbiota, and microbial fermentation of finishing pigs during a 14-day feeding period. The results showed that the average daily feed intake (ADFI) and feed/gain (F/G) of pigs were not affected as the dietary fiber increased. Apparent total tract digestibility (ATTD) of cellulose, hemicellulose, insoluble dietary fiber (IDF), soluble dietary fiber (SDF), and TDF of pigs remained unchanged when TDF was between 16.70 and 17.75%, while strikingly decreased when TDF increased from 17.75 to 24.11%. It is worth noting that increasing fiber intake seemed to favor hemicellulose digestion. In addition, the increase in fiber intake increased fecal microbial diversity, especially improved the proportion of the members of the family Prevotellaceae, Ruminococcaceae, and Lachnospiraceae, and decreased the abundance of the genus Streptococcus. Moreover, the increase in fiber intake promoted the digestion of fiber, production of short chain fatty acids (SCFAs), and enhanced microbial pyruvate metabolism and butanoate metabolism. In conclusion, short-term high fiber feeding has no adverse effects on the growth performance of finishing pigs. ATTD of dietary fiber of finishing pigs was maintained when TDF was at 17.75%. And short-term high fiber feeding improved microbial diversity and fiber degradation functions of finishing pigs.

Meat color is the primary criterion by which consumers evaluate meat quality. However, there are a few candidate genes and molecular markers of meat color that were reported for pig molecular breeding. The purpose of the present study is to identify the candidate genes affecting meat color and provide the theoretical basis for meat color molecular breeding. A total of 306 Suhuai pigs were slaughtered, and meat color was evaluated at 45 min and 24 h after slaughter by CIELAB color space. All individuals were genotyped using GeneSeek GGP-Porcine 80K SNP BeadChip. The genomic estimated breeding values (GEBVs), heritability, and genetic correlation of meat color were calculated by DMU software. The genome-wide association studies (GWASs) and the fixation index (FST) tests were performed to identify SNPs related to meat color, and the candidate genes within 1 Mb upstream and downstream of significant SNPs were screened by functional enrichment analysis. The heritability of L* 45 min, L* 24 h, a* 45 min, a* 24 h, b* 45 min, and b* 24 h was 0.20, 0.16, 0.30, 0.13, 0.29, and 0.22, respectively. The genetic correlation between a* (a* 45 min and a* 24 h) and L* (L* 45 min and L* 24 h) is strong, whereas the genetic correlation between b* 45 min and b* 24 h is weak. Forty-nine significant SNPs associated with meat color were identified through GWAS and FST tests. Among these SNPs, 34 SNPs were associated with L* 45 min within a 5-Mb region on Sus scrofa chromosome 11 (SSC11); 22 SNPs were associated with a* 45 min within a 14.72-Mb region on SSC16; six SNPs were associated with b* 45 min within a 4.22-Mb region on SSC13; 11 SNPs were associated with b* 24 h within a 2.12-Mb region on SSC3. These regions did not overlap with meat color–associated QTLs reported previously. Moreover, six candidate genes (HOMER1, PIK3CG, PIK3CA, VCAN, FABP3, and FKBP1B), functionally related to muscle development, phosphatidylinositol phosphorylation, and lipid binding, were detected around these significant SNPs. Taken together, our results provide a set of potential molecular markers for the genetic improvement of meat color in pigs.

A robust generalized labeled multi-Bernoulli (GLMB) filter is presented to perform multitarget tracking (MTT) with unknown non-stationary heavy-tailed measurement noise (HTMN). The HTMN is modeled as a multivariate Student’s t-distribution with unknown and time-varying mean. The proposed filter relaxes the restrictive assumption that the mean of HTMN is zero, and can effectively deal with MTT under the condition that the mean of HTMN is unknown and time-varying. The variational Bayesian (VB) approximation is applied in the GLMB filtering framework with the augmented state. The marginal likelihood function is obtained via minimizing the Kullback-Leibler divergence by the variational lower bound. The simulation results demonstrate that the proposed filter can effectively track multiple targets in both linear and nonlinear scenarios when the mean of HTMN is unknown and time-varying.

In this paper, two compact monopole antennas working at 149 MHz (VHF) and 398 MHz (UHF) are proposed for CubeSats applications. Two monopole antennas are integrated on a double layer ceramic substrate. The overall dimensions of the folded antenna are 101 mm × 40 mm × 8.9 mm which is very small. Meander-line technique and foldable structure are proposed to achieve a compact design. The introduction of decoupling structure solves the problem of high coupling caused by small size. Computer simulations and measurements are conducted. The results demonstrate that the proposed design is a very promising candidate for CubeSats applications.

Making full use of high fiber and low-cost crop coproducts is helpful to alleviate the situation of people and livestock competing for crops. Digestion of dietary fibers in pigs is mainly through microbial fermentation in the large intestine. To reveal microbiota related to fiber digestion in pigs, fecal samples have been collected from 274 healthy female Suhuai pigs at 160 days of age under the same feeding conditions and have measured apparent neutral detergent fiber (NDF) and acid detergent fiber (ADF) digestibility. Samples from Suhuai pigs with extreme high and low apparent NDF digestibility and extreme high and low apparent ADF digestibility were subjected to shotgun metagenomic sequencing. At the species level, 62 microbial species in H_NDF group and 54 microbial species in H_ADF group were related to high fiber digestibility. Among them, Lachnospiraceae bacterium 3-1 and Alistipes sp. CAG:514 may be new types of microorganisms associated with fiber digestion. In addition, we found that more abundant GH5 and GH48 family (contribute to cellulose degradation) genes, GH39 and GH53 family (contribute to hemicellulose degradation) genes in microorganisms may contribute to the higher apparent NDF digestibility of pigs, and more abundant GH3 and GH9 family (contribute to cellulose degradation) genes in microorganisms may contribute to the higher apparent ADF digestibility of pigs. The abundance of AA4 family (helps in lignin degradation) genes in H_NDF and H_ADF groups was significantly higher than that in L_NDF and L_ADF groups, respectively (P < 0.05). Three pathways in H_NDF group and four pathways in H_ADF group are important pathways associated with degradation of non-starch polysaccharides, and their relative abundance is significantly higher than that in L_NDF and L_ADF groups, respectively. Gut microbiota of Suhuai pigs with high apparent fiber digestibility had higher abundance of genes and microbiota related to fiber digestion and may have stronger fiber digestion potential compared with low apparent fiber digestibility group. This study revealed that the characteristics of gut microbiota and microbial gene functions of pigs with high fiber apparent digestibility, which provided a theoretical basis and reference for further understanding the impact of gut microbiota on fiber digestibility of pigs.

Skeletal muscle fiber types can contribute in part to affecting pork quality parameters. Biceps femoris (Bf) (fast muscle or white muscle) and Soleus (Sol) (slow muscle or red muscle) are two typical skeletal muscles characterized by obvious muscle fiber type differences in pigs. However, the critical proteins and potential regulatory mechanisms regulating porcine skeletal muscle fibers have yet to be clearly defined. In this study, the isobaric Tag for Relative and Absolute Quantification (iTRAQ)-based proteome was used to identify the key proteins affecting the skeletal muscle fiber types with Bf and Sol, by integrating the previous transcriptome data, while function enrichment analysis and a protein–protein interaction (PPI) network were utilized to explore the potential regulatory mechanisms of skeletal muscle fibers. A total of 126 differentially abundant proteins (DAPs) between the Bf and Sol were identified, and 12 genes were found to be overlapping between differentially expressed genes (DEGs) and DAPs, which are the critical proteins regulating the formation of skeletal muscle fibers. Functional enrichment and PPI analysis showed that the DAPs were mainly involved in the skeletal-muscle-associated structural proteins, mitochondria and energy metabolism, tricarboxylic acid cycle, fatty acid metabolism, and kinase activity, suggesting that PPI networks including DAPs are the main regulatory network affecting muscle fiber formation. Overall, these data provide valuable information for understanding the molecular mechanism underlying the formation and conversion of muscle fiber types, and provide potential markers for the evaluation of meat quality.

Vulvar size and angle are meaningful traits in pig production. Sows with abnormal vulva generally show reproductive disorders. In order to excavate candidate loci and genes associated with pig’s vulvar traits, 270 Suhuai pigs with vulvar phenotype were genotyped by a porcine single nucleotide polymorphisms (SNP) Chip. Then, Chip data were imputed using resequenced data of 30 Suhuai pigs as a reference panel. Next, we estimated the heritability and performed a genome-wide association study (GWAS) for vulvar traits. The heritabilities for the traits vulvar length (VL), vulvar width (VW) and vulvar angle (VA) in this pig population were 0.23, 0.32 and 0.22, respectively. GWAS based on Chip data identified nine significant SNPs on the Sus scrofa chromosomes (SSC) 2, 7, 9 and 13 for VL or VW. GWAS based on imputed data identified 11 new quantitative trait loci (QTL) on SSC1, 2, 7, 8, 9, 11, 13, 16 and 17 for VL or VW. The most significant QTL for VL on SSC2 were refined to a 3.48–3.97 Mb region using linkage disequilibrium and linkage analysis (LDLA). In this refined region, FGF19 and CCND1, involved in the development of the reproductive tract, cell growth and vulvar cancer, could be new candidate genes affecting VL. Our results provided potential genetic markers for the breeding of vulvar traits in pigs and deepened the understanding of the genetic mechanism of vulvar traits.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Although there are established mechanisms and preventions for CVDs, they are not totally elucidative and effective. Emerging evidence suggests that the dysregulation of ion channels in the cell membranes underpins the dysfunction of the cardiovascular system. To date, a variety of cation channels have been widely recognized as important targets for the treatment of CVDs. As a critical component of the anion channels, the volume-regulated anion channel (VRAC) is involved in a series of cell functions by the volume regulation and maintenance of membrane homeostasis. It has been confirmed to play crucial roles in cell action potential generation, cell proliferation, differentiation and apoptosis, and the VRAC appears to be a major participant in metabolic processes during CVDs. This review summarizes the current evidence and progress concerning the VRAC, to determine the future directions and challenges for CVDs for both preventive and therapeutic purposes.

The different skeletal muscle fiber types exhibit distinctively different physiological and metabolic properties, and have been linked to both human metabolic diseases and meat quality traits in livestock. Circular RNAs (circRNAs) are a new class of endogenous RNA regulating gene expression, but regulatory mechanisms of skeletal muscle fibers involved in circRNAs remain poorly understood. Here, we constructed circRNA expression profiles of three fast-twitch biceps femoris (Bf) and three slow-twitch soleus (Sol) muscles in pigs using RNA-seq and identified 16,342 distinct circRNA candidates. Notably, 242 differentially expressed (DE) circRNAs between Bf and Sol muscles were identified, including 105 upregulated and 137 downregulated circRNAs, and are thus potential candidates for the regulation of skeletal muscle fiber conversion. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of host genes of DE circRNAs revealed that host genes were mainly involved in skeletal muscle fiber-related GO terms (e.g., muscle contraction, contractile fiber part, and Z disk) and skeletal muscle fiber-related signaling pathways (e.g., AMPK and cGMP-PKG). We also constructed co-expression networks of DE circRNA-miRNA-mRNA using previously acquired high-throughput sequencing mRNA and miRNA data, from which 112 circRNA-miRNA and 95 miRNA-mRNA interactions were identified. Multiple circRNAs essentially serve as a sponge for miR-499-5p, which is preferentially expressed in slow-twitch muscle and reduces the severity of Duchenne muscular dystrophy (DMD). Taken together, a series of novel candidate circRNAs involved in the growth and development of porcine skeletal muscle was identified. Furthermore, they provide a comprehensive circRNA resource for further in-depth research on the regulatory mechanisms of circRNA in the formation of skeletal muscle fiber, and may provide insights into human skeletal muscle diseases.

Objective. The accelerate loss of skeletal muscle mass, strength, and function, named sarcopenia, is a progressive and generalised skeletal muscle disorder, and it is always associated with increased outcomes including falls, frailty, and disability. Diabetes mellitus is associated with significant muscle and physical complications. We aimed at clarifying the changes and risk factors of skeletal muscle mass and strength in elderly with type 2 diabetes. Methods. The study consisted of patients with type 2 diabetes (n=120) and an older general population (n=126). The skeletal muscle mass and muscle strength, as well as the serum levels of chronic inflammation, oxidative stress, homocysteine, and insulin-like factor-1 were assessed, and the correlation and regression analysis were conducted to evaluate outcomes. Results. T2DM patients exhibited lower muscle strength compared with the non-T2DM subjects (P

The vertnin (VRTN) gene g.20311_20312ins291 was reported as an important variant related to the number of ribs (RIB), and the ins/ins genotype was advantageous for improving RIB of Western pigs. The purpose of this study was to determine whether the VRTN gene g.20311_20312ins291 influences RIB, carcass traits, and body size traits, including cannon bone circumference (CBC) in Chinese Suhuai pigs. We found that the VRTN gene g.20311_20312ins291 was polymorphic in Suhuai fattening pigs and gilts. The polymorphism of g.20311_20312ins291 was significantly associated with RIB and CDL in Suhuai fattening pigs (p < 0.01), whereas this variant had no influence on carcass weight (CWT). There was a tendency of association between this variant and carcass straight length (CSL) in Suhuai fattening pigs (p = 0.06). The polymorphism of g.20311_20312ins291 was also significantly associated with CBC in Suhuai gilts (p = 0.04). Furthermore, CBC was positively genetically correlated with body length (0.22, p < 0.01) and body weight (0.15, p < 0.01). Our results indicated that the VRTN gene g.20311_20312ins291 could be used as a potential marker for improving RIB, CDL, and CBC in Suhuai pigs.

Lipoproteins are supramolecular assemblies of proteins and lipids with dynamic characteristics critically linked to their biological functions as plasma lipid transporters and lipid exchangers. Among them, spherical high-density lipoproteins are the most abundant forms of high-density lipoprotein (HDL) in human plasma, active participants in reverse cholesterol transport, and associated with reduced development of atherosclerosis. Here, we employed elastic incoherent neutron scattering (EINS) and hydrogen-deuterium exchange mass spectrometry (HDX-MS) to determine the average particle dynamics and protein backbone local mobility of physiologically competent discoidal and spherical HDL particles reconstituted with human apolipoprotein A-I (apoA-I). Our EINS measurements indicated that discoidal HDL was more dynamic than spherical HDL at ambient temperatures, in agreement with their lipid-protein composition. Combining small-angle neutron scattering (SANS) with contrast variation and MS cross-linking, we showed earlier that the most likely organization of the three apolipoprotein A-I (apoA-I) chains in spherical HDL is a combination of a hairpin monomer and a helical antiparallel dimer. Here, we corroborated those findings with kinetic studies, employing hydrogen-deuterium exchange mass spectrometry (HDX-MS). Many overlapping apoA-I digested peptides exhibited bimodal HDX kinetics behavior, suggesting that apoA-I regions with the same amino acid composition located on different apoA-I chains had different conformations and/or interaction environments.

In this paper, an image recovery problem under the case of salt-and-pepper noise and data missing that degrade image quality is addressed if they are not effectively handled, where the salt-and-pepper noise as the impulsive noise is remodeled as a sparse signal due to its impulsiveness and the data missing pattern, denoted by a sparse vector, contains only zeros and ones to formulate the data missing. In particular, the salt-and-pepper noise and data missing are reformatted by their sparsity, respectively. The wavelet and framelet domains are explored to sparsely represent the image in order to accurately reconstruct the clean image. From the reformulations conducted and to recover the image, under one optimization framework, a joint estimation is developed to perform the image recovery, the salt-and-pepper noise suppression, and the missing patter estimation. To solve the optimization problem, two efficient solvers are developed to obtain the joint estimation solution, and they are based on the alternating direction method of multipliers (ADMM) and accelerated proximal gradient (APG). Finally, numerical studies verify that the joint estimation algorithm outperforms the state-of-the-art approaches in terms of both objective and subjective evaluation standards.

A new optimization algorithm of sensor selection is proposed in this paper for decentralized large-scale multi-target tracking (MTT) network within a labeled random finite set (RFS) framework. The method is performed based on a marginalized δ-generalized labeled multi-Bernoulli RFS. The rule of weighted Kullback-Leibler average (KLA) is used to fuse local multi-target densities. A new metric, named as the label assignment (LA) metric, is proposed to measure the distance for two labeled sets. The lower bound of LA metric based mean square error between the labeled multi-target state set and its estimate is taken as the optimized objective function of sensor selection. The proposed bound is obtained by the information inequality to RFS measurement. Then, we present the sequential Monte Carlo and Gaussian mixture implementations for the bound. Another advantage of the bound is that it provides a basis for setting the weights of KLA. The coordinate descent method is proposed to compromise the computational cost of sensor selection and the accuracy of MTT. Simulations verify the effectiveness of our method under different signal-to- noise ratio scenarios.

The PAF complex (Paf1C) has been shown to regulate chromatin modifications, gene transcription, and RNA polymerase II (PolII) elongation. Here, we provide the first genome-wide profiles for the distribution of the entire complex in mammalian cells using chromatin immunoprecipitation and high throughput sequencing. We show that Paf1C is recruited not only to promoters and gene bodies, but also to regions downstream of cleavage/polyadenylation (pA) sites at 3' ends, a profile that sharply contrasted with the yeast complex. Remarkably, we identified novel, subunit-specific links between Paf1C and regulation of alternative cleavage and polyadenylation (APA) and upstream antisense transcription using RNAi coupled with deep sequencing of the 3' ends of transcripts. Moreover, we found that depletion of Paf1C subunits resulted in the accumulation of PolII over gene bodies, which coincided with APA. Depletion of specific Paf1C subunits led to global loss of histone H2B ubiquitylation, although there was little impact of Paf1C depletion on other histone modifications, including tri-methylation of histone H3 on lysines 4 and 36 (H3K4me3 and H3K36me3), previously associated with this complex. Our results provide surprising differences with yeast, while unifying observations that link Paf1C with PolII elongation and RNA processing, and indicate that Paf1C subunits could play roles in controlling transcript length through suppression of PolII accumulation at transcription start site (TSS)-proximal pA sites and regulating pA site choice in 3'UTRs.

The existing multi-sensor control algorithms for multi-target tracking (MTT) within the random finite set (RFS) framework are all based on the distributed processing architecture, so the rule of generalized covariance intersection (GCI) has to be used to obtain the multi-sensor posterior density. However, there has still been no reliable basis for setting the normalized fusion weight of each sensor in GCI until now. Therefore, to avoid the GCI rule, the paper proposes a new constrained multi-sensor control algorithm based on the centralized processing architecture. A multi-target mean-square error (MSE) bound defined in our paper is served as cost function and the multi-sensor control commands are just the solutions that minimize the bound. In order to derive the bound by using the generalized information inequality to RFS observation, the error between state set and its estimation is measured by the second-order optimal sub-pattern assignment metric while the multi-target Bayes recursion is performed by using a δ-generalized labeled multi-Bernoulli filter. An additional benefit of our method is that the proposed bound can provide an online indication of the achievable limit for MTT precision after the sensor control. Two suboptimal algorithms, which are mixed penalty function (MPF) method and complex method, are used to reduce the computation cost of solving the constrained optimization problem. Simulation results show that for the constrained multi-sensor control system with different observation performance, our method significantly outperforms the GCI-based Cauchy-Schwarz divergence method in MTT precision. Besides, when the number of sensors is relatively large, the computation time of the MPF and complex methods is much shorter than that of the exhaustive search method at the expense of completely acceptable loss of tracking accuracy.

Fibroblast growth factor 21 (FGF21) plays an important role in the treatment of disease associated with muscle insulin resistance which is characterized by various factors, such as intramuscular triglyceride (IMT) content. Studies have also shown that FGF21 inhibits triglyceride synthesis in vivo. However, the precise mechanism whereby FGF21 regulates triglyceride metabolism in intramuscular fat (IMF), which may influence the muscle insulin sensitivity, is not clearly understood. In order to understand the role of FGF21 in IMF deposition, we performed FGF21 overexpression in IMF cells by stable transfection. Our results showed that FGF21 inhibited the key adipogenesis gene mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG), CCAAT/enhancer-binding protein (CEBP) family by reducing lysine-specific demethylase 1 (LSD1) expression which led to significant decline in lipid accumulation, and the result was confirmed by Western blot. Moreover, triggered by FGF21, parts of the adipokines—fatty acid-binding protein 4 (FABP4), glucose transporter 4 (GLUT4), adiponectin (ADIPOQ), and perilipin (PLIN1)—were also down-regulated. Furthermore, FGF21 gene expression was suppressed by transcription factor CEBP beta (CEBPB) which contributed strongly to triglyceride synthesis. Taken together, our study is the first to experimentally demonstrate FGF21 emerging as an efficient blockade of adipogenesis in IMF, thus also providing a new understanding of the mechanism whereby FGF21 improves insulin sensitivity.

BACKGROUND. Frailty significantly affects morbidity and mortality rates in the older population (age >65 years). Age-related degenerative diseases are influenced by the intestinal microbiota. However, limited research exists on alterations in the intestinal microbiota in frail older individuals, and the effectiveness of prebiotic intervention for treating frailty remains uncertain. OBJECTIVE. We sought to examine the biological characteristics of the intestinal microbiome in frail older individuals and assess changes in both frailty status and gut microbiota following intervention with a prebiotic blend consisting of inulin and oligofructose. METHODS. The study consisted of 3 components: an observational analysis with a sample size of 1,693, a cross-sectional analysis (n = 300), and a multicenter double-blind, randomized, placebo-controlled trial (n = 200). Body composition, commonly used scales, biochemical markers, intestinal microbiota, and metabolites were examined in 3 groups of older individuals (nonfrail, prefrail, and frail). Subsequently, changes in these indicators were reevaluated after a 3-month intervention using the prebiotic mixture for the prefrail and frail groups. RESULTS. The intervention utilizing a combination of prebiotics significantly improved frailty and renal function among the older population, leading to notable increases in protein levels, body fat percentage, walking speed, and grip strength. Additionally, it stimulated an elevation in gut probiotic count and induced alterations in microbial metabolite expression levels as well as corresponding metabolic pathways. CONCLUSIONS. The findings suggest a potential link between changes in the gut microbiota and frailty in older adults. Prebiotics have the potential to modify the gut microbiota and metabolome, resulting in improved frailty status and prevention of its occurrence. [ABSTRACT FROM AUTHOR]

The utility of bivalent dimeric glutathione S-tranferase (GST) inhibitors and their optimization via combinatorial liner design are demonstrated. Protein binding site mapping done using H/D mass exchange spectroscopy indicates that peptides within the intersubunit cleft and in the substrate binding site are protected by inhibitor from solvent exchange.

We explain the stimulating effect of digital payments on households' consumption using mental accounting theory. With the China Household Finance Survey (CHFS) data in 2017, we empirically identify that households who use digital payments spend 20.63% more than those with alternative payment methods. From the mental accounting perspective, we argue that using digital payments increase consumers' transaction utility, facilitate intentional adjustment of mental accounts, and result in more unplanned consumption. The stimulating effect is more substantial on long-term consumption and among households with low self-control abilities. Moreover, the integrated financial services provide access to liquidity and help smooth consumption. [ABSTRACT FROM AUTHOR]

Tau pathology initiates in defined brain regions and is known to spread along neuronal connections as symptoms progress in Alzheimer's disease (AD) and other tauopathies. This spread requires the release of tau from donor cells, but the underlying molecular mechanisms remained unknown. Here, we established the interactome of the C-terminal tail region of tau and identified syntaxin 8 (STX8) as a mediator of tau release from cells. Similarly, we showed the syntaxin 6 (STX6), part of the same SNARE family as STX8 also facilitated tau release. STX6 was previously genetically linked to progressive supranuclear palsy (PSP), a tauopathy. Finally, we demonstrated that the transmembrane domain of STX6 is required and sufficient to mediate tau secretion. The differential role of STX6 and STX8 in alternative secretory pathways suggests the association of tau with different secretory processes. Taken together, both syntaxins, STX6 and STX8, may contribute to AD and PSP pathogenesis by mediating release of tau from cells and facilitating pathology spreading. [ABSTRACT FROM AUTHOR]

Elongin is an RNA polymerase II (RNAPII)-associated factor that has been shown to stimulate transcriptional elongation in vitro. The Elongin complex is thought to be required for transcriptional induction in response to cellular stimuli and to ubiquitinate RNAPII in response to DNA damage. Yet, the impact of the Elongin complex on transcription in vivo has not been well studied. Here, we performed comprehensive studies of the role of Elongin A, the largest subunit of the Elongin complex, on RNAPII transcription genome-wide. Our results suggest that Elongin A localizes to actively transcribed regions and potential enhancers, and the level of recruitment correlated with transcription levels. We also identified a large group of factors involved in transcription as Elongin A-associated factors. In addition, we found that loss of Elongin A leads to dramatically reduced levels of serine2-phosphorylated, but not total, RNAPII, and cells depleted of Elongin A show stronger promoter RNAPII pausing, suggesting that Elongin A may be involved in the release of paused RNAPII. Our RNA-seq studies suggest that loss of Elongin A did not alter global transcription, and unlike prior in vitro studies, we did not observe a dramatic impact on RNAPII elongation rates in our cell-based nascent RNA-seq experiments upon Elongin A depletion. Taken together, our studies provide the first comprehensive analysis of the role of Elongin A in regulating transcription in vivo. Our studies also revealed that unlike prior in vitro findings, depletion of Elongin A has little impact on global transcription profiles and transcription elongation in vivo. [ABSTRACT FROM AUTHOR]

Lipoproteins are supramolecular assemblies of proteins and lipids with dynamic characteristics critically linked to their biological functions as plasma lipid transporters and lipid exchangers. Among them, spherical high-density lipoproteins are the most abundant forms of high-density lipoprotein (HDL) in human plasma, active participants in reverse cholesterol transport, and associated with reduced development of atherosclerosis. Here, we employed elastic incoherent neutron scattering (EINS) and hydrogen-deuterium exchange mass spectrometry (HDX-MS) to determine the average particle dynamics and protein backbone local mobility of physiologically competent discoidal and spherical HDL particles reconstituted with human apolipoprotein A-I (apoA-I). Our EINS measurements indicated that discoidal HDL was more dynamic than spherical HDL at ambient temperatures, in agreement with their lipid-protein composition. Combining small-angle neutron scattering (SANS) with contrast variation and MS cross-linking, we showed earlier that the most likely organization of the three apolipoprotein A-I (apoA-I) chains in spherical HDL is a combination of a hairpin monomer and a helical antiparallel dimer. Here, we corroborated those findings with kinetic studies, employing hydrogen-deuterium exchange mass spectrometry (HDX-MS). Many overlapping apoA-I digested peptides exhibited bimodal HDX kinetics behavior, suggesting that apoA-I regions with the same amino acid composition located on different apoA-I chains had different conformations and/or interaction environments. [ABSTRACT FROM AUTHOR]

NMR study is conducted for the detailed knowledge of the metal-A(beta) coordination environment's contribution in the development of compounds with more effective and specific metal chelating properties for the treatment of Alzheimer's disease. It is suggested that the NMR study uncovers unique binding properties between copper and the A(beta) peptide in solution at pH 7.3.

The pathogenesis of Alzheimer's disease is characterized by the aggregation and fibrillation of the 40-residue Abeta(1-40) and Abeta(1-42) peptides into amyloid plaques. Oxidation of the methionine-35 side chain to the sulfoxide significantly impedes the rate of aggregation and fibrillation of the Abeta peptide.

Elongation factor Paf1C regulates several stages of the RNA polymerase II (Pol II) transcription cycle, although it is unclear how it modulates Pol II distribution and progression in mammalian cells. We found that conditional ablation of Paf1 resulted in the accumulation of unphosphorylated and Ser5 phosphorylated Pol II around promoter-proximal regions and within the first 20 to 30 kb of gene bodies, respectively. Paf1 ablation did not impact the recruitment of other key elongation factors, namely, Spt5, Spt6, and the FACT complex, suggesting that Paf1 function may be mechanistically distinguishable from each of these factors. Moreover, loss of Paf1 triggered an increase in TSS-proximal nucleosome occupancy, which could impose a considerable barrier to Pol II elongation past TSS-proximal regions. Remarkably, accumulation of Ser5P in the first 20 to 30 kb coincided with reductions in histone H2B ubiquitylation within this region. Furthermore, we show that nascent RNA species accumulate within this window, suggesting a mechanism whereby Paf1 loss leads to aberrant, prematurely terminated transcripts and diminution of full-length transcripts. Importantly, we found that loss of Paf1 results in Pol II elongation rate defects with significant rate compression. Our findings suggest that Paf1C is critical for modulating Pol II elongation rates by functioning beyond the pause-release step as an "accelerator" over specific early gene body regions. [ABSTRACT FROM AUTHOR]

Apolipoprotein A-I (apoA-I), the main protein constituent of HDLs, increases insulin synthesis and insulin secretion in pancreatic β cells. ApoA-I also accepts cholesterol that effluxes from cells expressing ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1). Mice with conditional deletion of ABCA1 and ABCG1 in β cells [β-double knockout (DKO) mice] have increased islet cholesterol levels and reduced glucose-stimulated insulin secretion (GSIS). The project asks whether metabolic pathways are dysregulated in β-DKO mouse islets and whether this can be corrected, and GSIS improved, by treatment with apoA-I. β-DKO mice were treated with apoA-I or PBS, and islets were isolated for determination of GSIS. Total RNA was extracted from β-DKO and control mouse islets for microarray analysis. Metabolic pathways were interrogated by functional enrichment analysis. ApoA-I treatment improved GSIS in β-DKO but not control mouse islets. Plasma lipid and lipoprotein levels and islet cholesterol levels were also unaffected by treatment with apoA-I. Cholesterol metabolism, glucose metabolism, and inflammation pathways were dysregulated in β-DKO mouse islets. This was not corrected by treatment with apoA-I. In summary, apoA-I treatment improves GSIS by a cholesterol-independent mechanism, but it does not correct metabolic dysregulation in β-DKO mouse islets.--Hou, L., Tang, S., Wu, B. J., Ong, K.-L., Westerterp, M., Barter, P. J., Cochran, B. J., Tabet, F., Rye, K.-A. Apolipoprotein A-I improves pancreatic β-cell function independent of the ATP-binding cassette transporters ABCA1 and ABCG1. [ABSTRACT FROM AUTHOR]

Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP-binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice). Insulin secretion was impaired in these mice under basal and high-glucose conditions, and glucose disposal was shifted from skeletal muscle to adipose tissue. The β-DKO mice also had increased body fat and adipose tissue macrophage content, elevated plasma interleukin-6 and MCP-1 levels, and decreased skeletal muscle mass. They were not, however, insulin resistant. The adipose tissue expansion and reduced skeletal muscle mass, but not the systemic inflammation or increased adipose tissue macrophage content, were reversed when plasma insulin levels were normalized by insulin supplementation. These studies identify a mechanism by which perturbation of β-cell cholesterol homeostasis and impaired insulin secretion increase adiposity, reduce skeletal muscle mass, and cause systemic inflammation. They further identify β-cell dysfunction as a potential therapeutic target in people at increased risk of developing type 2 diabetes. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 21 (FGF21) plays an important role in the treatment of disease associated with muscle insulin resistance which is characterized by various factors, such as intramuscular triglyceride (IMT) content. Studies have also shown that FGF21 inhibits triglyceride synthesis in vivo. However, the precise mechanism whereby FGF21 regulates triglyceride metabolism in intramuscular fat (IMF), which may influence the muscle insulin sensitivity, is not clearly understood. In order to understand the role of FGF21 in IMF deposition, we performed FGF21 overexpression in IMF cells by stable transfection. Our results showed that FGF21 inhibited the key adipogenesis gene mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG), CCAAT/enhancer-binding protein (CEBP) family by reducing lysine-specific demethylase 1 (LSD1) expression which led to significant decline in lipid accumulation, and the result was confirmed by Western blot. Moreover, triggered by FGF21, parts of the adipokines—fatty acid-binding protein 4 (FABP4), glucose transporter 4 (GLUT4), adiponectin (ADIPOQ), and perilipin (PLIN1)—were also down-regulated. Furthermore, FGF21 gene expression was suppressed by transcription factor CEBP beta (CEBPB) which contributed strongly to triglyceride synthesis. Taken together, our study is the first to experimentally demonstrate FGF21 emerging as an efficient blockade of adipogenesis in IMF, thus also providing a new understanding of the mechanism whereby FGF21 improves insulin sensitivity. [ABSTRACT FROM AUTHOR]