Chronic stress causes dysregulations of mood and energy homeostasis, but the neurocircuitry underlying these alterations remain to be fully elucidated. Here we demonstrate that chronic restraint stress in mice results in hyperactivity of pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus (POMC ARH neurons) associated with decreased neural activities of dopamine neurons in the ventral tegmental area (DA VTA neurons). We further revealed that POMC ARH neurons project to the VTA and provide an inhibitory tone to DA VTA neurons via both direct and indirect neurotransmissions. Finally, we show that photoinhibition of the POMC ARH →VTA circuit in mice increases body weight and food intake, and reduces depression-Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Brain glucose-sensing neurons detect glucose fluctuations and prevent severe hypoglycemia, but mechanisms mediating functions of these glucose-sensing neurons are unclear. Here we report that estrogen receptor-α (ERα)-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH) can sense glucose fluctuations, being glucose-inhibited neurons (GI-ERα vlVMH) or glucose-excited neurons (GE-ERα vlVMH). Hypoglycemia activates GI-ERα vlVMH neurons via the anoctamin 4 channel, and inhibits GE-ERα vlVMH neurons through opening the ATP-sensitive potassium channel. Further, we show that GI-ERα vlVMH neurons preferentially project to the medioposterior arcuate nucleus of the hypothalamus (mpARH) and GE-ERα vlVMH neurons preferentially project to the dorsal Raphe nuclei (DRN). Activation of ERα vlVMH to mpARH circuit and inhibition of ERα vlVMH to DRN circuit both increase blood glucose. Thus, our results indicate that ERα vlVMH neurons detect glucose fluctuations and prevent severe hypoglycemia in mice.
Fat and lean pig breeds show obvious differences in meat quality characteristics including the fatty acid composition of muscle. However, the molecular mechanism underlying these phenotypes differences remains unknown. This study compared meat quality traits between Lantang (a Chinese indigenous breed) and Landrace (a typical lean breed). The Lantang pigs showed higher L* values and intramuscular fat content, lower pH45min, pH24h and shear force in longissimus dorsi (LD) muscle than Landrace (P < 0.05). Fatty acid analysis demonstrated the lower monounsaturated fatty acids (MUFA) and higher polyunsaturated fatty acids (PUFA) percentage in Lantang LD than that in Landrace LD (P < 0.05). To further identify candidate genes for fatty acid composition, the transcriptome of LD muscle from the two breeds were measured by microarrays. There were 586 transcripts differentially expressed, of which 267 transcripts were highly expressed in Lantang pigs. After the validation by real-time quantitative PCR, 13 genes were determined as candidate genes for fatty acid composition of muscle, including Stearoyl-CoA desaturase (SCD). Then, a SCD over-expression plasmid was transfected into C2C12 cells to reveal the effect of SCD on the fatty acid composition in vitro. The results showed that SCD over-expression significantly increased PUFA proportion, while reduced that of saturated fatty acids (SFA) in C2C12 cells (P < 0.05). In summary, this study compared the differences of fatty acid composition and transcriptome in two breeds differing in meat quality, and further identified the novel role of SCD in the regulation of PUFA deposition.
Pig is an important agricultural animal for meat production and provides a valuable model for many human diseases. Functional studies have demonstrated that microRNAs (miRNAs) play critical roles in almost all aspects of skeletal muscle development and disease pathogenesis. To investigate the miRNAs involved in regulating different periods of skeletal muscle development, we herein performed a comprehensive research for porcine microRNAome (miRNAome) during 10 skeletal muscle developmental stages including 35, 49, 63, 77, 91 dpc (days post coitum) and 2, 28, 90, 120, 180 dpn (days postnatal) using Solexa sequencing technology. Our results extend the repertoire of pig miRNAome to 247 known miRNAs processed from 210 pre-miRNAs and 297 candidate novel miRNAs through comparison with known miRNAs in the miRBase. Expression analysis of the 15 most abundant miRNAs in every library indicated that functional miRNAome may be smaller and tend to be highly expressed. A series of muscle-related miRNAs summarized in our study present different patterns between myofibers formation phase and muscle maturation phase, providing valuable reference for investigation of functional miRNAs during skeletal muscle development. Analysis of temporal profiles of miRNA expression identifies 18 novel candidate myogenic miRNAs in pig, which might provide new insight into regulation mechanism mediated by miRNAs underlying muscle development.
Backgroud: This study aimed to determine the effects of early antibiotic intervention (EAI) on subsequent blood parameters, apparent nutrient digestibility, and fecal fermentation profile in pigs with different dietary crude protein (CP) levels. Eighteen litters of piglets (total 212) were randomly allocated to 2 groups and were fed a creep feed diet with or without in-feed antibiotics (olaquindox, oxytetracycline calcium and kitasamycin) from postnatal d 7 to d 42. On d 42, the piglets within the control or antibiotic group were mixed, respectively, and then further randomly assigned to a normal- ( Results: EAI increased (P < 0.05) albumin and glucose concentrations in low-CP diet on d 77, and increased (P < 0.05) urea concentration in normal-CP diet. On d 185, EAI increased (P < 0.05) globulin concentration in normal-CP diets, but decreased glucose concentration. For nutrient digestibility, EAI increased (P < 0.05) digestibility of CP on d 77. For fecal microbiota, the EAI as well as low-CP diet decreased (P < 0.05) E. coli count on d 77. For fecal metabolites, on d 77, EAI decreased (P < 0.05) total amines concentration but increased skatole concentration in low-CP diet. On d 185, the EAI increased (P < 0.05) putrescine and total amines concentrations in low-CP diets but reduced (P < 0.05) in the normal-CP diets. The low-CP diet decreased the concentrations of these compounds. Conclusions: Collectively, these results indicate that EAI has short-term effects on the blood parameters and fecal microbial fermentation profile. The effects of EAI varied between CP levels, which was characterized by the significant alteration of glucose and putrescine concentration.
In-feed antibiotics have been used to promote growth in piglets, but its impact on metabolomics profiles associated with host metabolism is largely unknown. In this study, to test the hypothesis that antibiotic treatment may affect metabolite composition both in the gut and host biofluids, metabolomics profiles were analyzed in antibiotic-treated piglets. Piglets were fed a corn-soy basal diet with or without in-feed antibiotics from postnatal day 7 to day 42. The serum biochemical parameters, metabolomics profiles of the serum, urine, and jejunal digesta, and indicators of microbial metabolism (short-chain fatty acids and biogenic amines) were analyzed. Compared to the control group, antibiotics treatment did not have significant effects on serum biochemical parameters except that it increased (P < 0.05) the concentration of urea. Antibiotics treatment increased the relative concentrations of metabolites involved in amino-acid metabolism in the serum, while decreased the relative concentrations of most amino acids in the jejunal content. Antibiotics reduced urinary 2-ketoisocaproate and hippurate. Furthermore, antibiotics decreased (P < 0.05) the concentrations of propionate and butyrate in the feces. Antibiotics significantly affected the concentrations of biogenic amines, which are derived from microbial amino-acid metabolism. The three major amines, putrescine, cadaverine, and spermidine, were all increased (P < 0.05) in the large intestine of antibiotics-treated piglets. These results identified the phenomena that in-feed antibiotics may have significant impact on the metabolomic markers of amino-acid metabolism in piglets.
SummaryShort‐chain fatty acids (SCFAs), particularly butyrate, are known to suppress inflammation, and regulate the gut bacterial ecology. However, little is known about propionate. We report here that propionate infusion in the caecum dramatically affected the structure of colonic microbiota of pigs based on 16s rRNA high‐throughput sequencing. Sixteen pig models were perfused with saline or sodium propionate by a fistula in the caecum. At d 28, all pigs were slaughtered for analysing bacterial metabolites, colonic microbiota and the expression of genes related to inflammation. The results showed that caecal infusion of sodium propionate increased the concentration of propionate and decreased the butyrate concentration in colonic content. For biogenic amines, the tyramine concentration was increased, while the concentration of cadaverine was decreased by infusion of sodium propionate. Furthermore, at the level of phylum, propionate increased the abundance of Bacteroidetes and reduced the abundance of Firmicutes. Prevotella and Bacteroides counts were increased, while Turicibacter abundance was decreased at the level of genus. Real‐time qPCR showed that the expression of NF‐κB and IL‐18 was upregulated by propionate infusion, whereas no significant differences were observed for the expression of other genes related to inflammatory processes. Taken together, these results provide a new evidence for the role of short‐chain fatty acid propionate on the composition of microbial community and inflammatory cytokines.
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