scholarly journals Maternal Dicer Knockout Impairs Growth and Gut Health in Nursing Wild-type Pups in Mice (P11-137-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Fang Zhou ◽  
Janos Zempleni
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Villous Atrophy ◽  
Conditional Knockout ◽  
Vehicle Body ◽  
Milk Consumption ◽  
Gut Health ◽  
Wild Type ◽  
Microrna Biogenesis ◽  
Fat Accretion

Abstract Objectives Background: Dicer catalyzes microRNA biogenesis. Administration of tamoxifen to heterozygous Dicer conditional knockout (KO) mice (Dicer + /-) deletes one Dicer allele (Dicer KO). Nanoparticles (exosomes) transfer microRNAs from donor cells to recipient cells. Humans absorb exosomes and microRNA cargos from milk. MicroRNAs regulate the expression of 60% of mammalian genes. Objectives: Assess whether the loss of microRNA biogenesis in lactating Dicer KO dams impairs growth and gut health in nursing wild-type pups. Methods Newborn pups from wild-type (WT) C57BL/6 breeders were fostered to synchronized Dicer + /- dams. Dams were injected with tamoxifen or vehicle (control). Additional controls included WT pups fostered to WT dams injected with tamoxifen or vehicle. Body weight gain and milk consumption were measured at timed intervals up to 21 days when pups were euthanized. Body fat accretion was assessed using NMR. Sections of the gastrointestinal tract were evaluated by histology analyses. The unpaired t-test was used for statistical analysis (tamoxifen vs. vehicle); P < 0.05 was considered statistically significant. Results Body weight and fat accretion in male and female pups nursed by Dicer KO dams was significantly lower than in vehicle controls at age 3 weeks (Figs. 1 and 2). Histology assessment revealed villous atrophy in the small intestine from pups nursed by Dicer KO dams compared to vehicle controls at age 3 weeks (Figs. 3–5). Tamoxifen administration did not elicit phenotypes in wild-type pups nursed by wild-type dams (not shown). Milk consumption was not significantly different between pups nursed by Dicer KO dams and controls (not shown). Conclusions Loss of microRNA biogenesis in lactating Dicer KO dams impairs growth and gut health in nursing wild-type pups. The quality of milk secreted by Dicer KO dams remains to be assessed. Funding Sources NIFA, NIH, Gerber Foundation, Gates Foundation, PureTech, Inc. and USDA Hatch and Multistate. J.Z. is a consultant for PureTech. Supporting Tables, Images and/or Graphs

scholarly journals Modulation of HIF-2α PAS-B domain contributes to physiological responses

2018 ◽  
Vol 115 (52) ◽  
pp. 13240-13245 ◽  
Author(s):  
Zhihui Feng ◽  
Xuan Zou ◽  
Yaomin Chen ◽  
Hanzhi Wang ◽  
Yingli Duan ◽  
...  
Keyword(s):  
Body Weight ◽  
Metabolic Regulation ◽  
Body Weight Gain ◽  
Metabolic Stress ◽  
Vital Role ◽  
Mutant Mice ◽  
Single Mutation ◽  
Wild Type ◽  
Adipose Mass

Hypoxia-inducible factors (HIFs) are transcription factors in the basic helix–loop–helix PER-ARNT-SIM (bHLH-PAS) protein family that contain internal hydrophobic cavities within their PAS-A and PAS-B domains. Among HIFs, the HIF-2α PAS-B domain contains a relatively large cavity exploited for the development of specific artificial ligands such as PT2399. Administration of PT2399 could suppress HIF-2α target gene expression without affecting HIF-1 activity in mice under hypoxia conditions. A single mutation (S305M) within the HIF-2α PAS-B domain suppressed HIF-2α activity while conferring resistance to PT2399 in vivo, indicating the vital role of PAS-B domain in HIF-2α hypoxia response. In contrast, the mutant mice did not phenocopy PT2399 intervention in wild-type mice under metabolic stress. Under a high-fat diet (HFD), the mutant mice exert enhanced adipogenesis and obtain larger adipose mass and body weight gain compared to wild type. However, administration of PT2399 along with HFD feeding sufficiently suppressed HFD-induced body weight and adipose mass increase through suppression of adipogenesis and lipogenesis. The accompanying decreased lipid accumulation in the liver and improved glucose tolerance in wild-type mice were not observed in the mutant mice indicating negative regulation of HIF-2α on obesity and a complex role for the PAS-B domain in metabolic regulation. Notably, short-term administration of PT2399 to obese mice decreased adipose mass and improved metabolic condition. These results indicate a regulatory role for HIF-2α in obesity progression and suggest a therapeutic opportunity for PT2399 in obesity and associated metabolic disorders.

Effect of artificial suckling devices on behaviour, adaptation pattern and growth performance of early weaned piglets

2015 ◽  
Author(s):  
SPACE Imtiwati ◽  
Sanjay Kumar ◽  
Superna Sharma ◽  
M. Patel ◽  
D. V. Singh ◽  
...  
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Milk Consumption ◽  
Early Weaning ◽  
Large White ◽  
Adaptation Pattern ◽  
Suckling Piglets ◽  
T1 And T2 ◽  
And Control ◽  
Better Than

Eighteen Large White Yorkshire piglets weaned at 10 ±2 days were divided randomly into three groups (n=6) and each group was allotted to circular (T1), horizontal (T2) device and control (T3). Piglets in T3 were reared with sow through natural suckling. Piglets were acclimatised for 5 days; during this period milk was given at the rate 25 ml per piglets four times daily. Further, during first, second, third and forth fortnights feeding continued at the rate of 100, 150 and 200 ml for four, three and two times daily in T1 and T2 devices respectively. Piglets were observed for behaviour, adaptation pattern and average milk consumption time daily, while body weight gained was recorded fortnightly. 100% of piglets in T3 showed non-nutritive suckling, belly nosing, massaging and teat order behaviours, but no such observations were recorded in T1 and T2. Adaptation pattern of piglets in T1 was 66.7 % and 100% in T2 and T3. Effects of suckling devices on average milk consumption time were 10.09 % and 13.79 % lower (Pe″0.05) in T1 and T2 device respectively compared to T3. Mean body weight gain in T1 and T2 devices were 5.12% and 16.89 % higher than T3. Horizontal suckling device (T2) performed better than T1 and T3 (control). Hence it can be recommended for early weaning in piglets.

scholarly journals Effects of supplemental xylanase and xylooligosaccharides on production performance and gut health variables of broiler chickens

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amit K. Singh ◽  
Birendra Mishra ◽  
Michael R. Bedford ◽  
Rajesh Jha
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Feed Intake ◽  
Body Weight Gain ◽  
Average Daily Gain ◽  
The Body ◽  
Production Performance ◽  
Gut Health ◽  
Final Body Weight ◽  
Total Period

Abstract Background This study evaluated the effects of supplemental xylanase and xylooligosaccharides (XOS) in a corn-soybean meal (SBM)-based diet on growth performance and intestinal health of broilers. A total of 288 day-old chicks (Cobb 500) were allocated to 36 floor pens (8 birds/pen) equally in 9 dietary treatments in a 3 × 3 factorial arrangement. The treatments were combinations of 3 levels of xylanase (0, 0.005% and 0.01% Econase XT) and 3 levels of prebiotics (0, 0.005% and 0.01% XOS) added to basal mash diets formulated in three phases (starter, d 0–14; grower, d 15–28; finisher, d 29–42). The feed intake and body weights were recorded weekly. On d 42, ileal sections were collected for histomorphometric and gene expression analysis, and cecal content was collected for determining short-chain fatty acids (SCFA) and microbiota. Results Xylanase linearly (P < 0.01) increased the average daily gain (ADG) in both the finisher and total period and the final body weight gain (FBWG, 2940 & 2932 vs. 2760 g) of broilers. XOS did not significantly increase either ADG or FBWG (P > 0.05). Supplemental xylanase and XOS did not affect average daily feed intake and feed conversion ratio (P > 0.05). Xylanase and XOS did not change villus height (VH) or crypt depth (CD) ratio (P > 0.05). However, xylanase exhibited a trend (P = 0.097) on VH:CD ratio. The inclusion of 0.01% XOS without xylanase increased the level of IL-10 (a marker of anti-inflammatory cytokine) and IL-4 (a T-cell differentiation cytokine) genes compared with control (P < 0.05). The acetate production was increased by xylanase (P < 0.01) and XOS (P < 0.05) without an additive effect. Xylanase increased total SCFA (P < 0.01) while XOS had a tendency to increase (P = 0.052). Alpha and beta diversity of microbiota among treatments were not different (P > 0.05). However, the mean proportion of family Ruminococcaceae was increased by the supplemental 0.01% xylanase (P < 0.01). Conclusion It can be concluded that XOS can enhance cecal fermentation, while xylanase can increase the body weight gain along with the fermentation metabolites in the ceca of broilers fed the corn-SBM-based diet but the effects may not always translate into an improved mucosal absorptive capacity and a better feed efficiency.

Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models

2018 ◽  
Vol 10 (472) ◽  
pp. eaat3392 ◽  
Author(s):  
Elizabeth A. Killion ◽  
Jinghong Wang ◽  
Junming Yie ◽  
Stone D.-H. Shi ◽  
Darren Bates ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Body Weight Gain ◽  
Association Studies ◽  
Conditional Knockout ◽  
Genome Wide Association Studies ◽  
Knockout Mouse Model ◽  
Conditional Knockout Mouse ◽  
Glucagon Like Peptide 1 ◽  
Treatment Of Obesity

Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) has been identified in multiple genome-wide association studies (GWAS) as a contributor to obesity, and GIPR knockout mice are protected against diet-induced obesity (DIO). On the basis of this genetic evidence, we developed anti-GIPR antagonistic antibodies as a potential therapeutic strategy for the treatment of obesity and observed that a mouse anti-murine GIPR antibody (muGIPR-Ab) protected against body weight gain, improved multiple metabolic parameters, and was associated with reduced food intake and resting respiratory exchange ratio (RER) in DIO mice. We replicated these results in obese nonhuman primates (NHPs) using an anti-human GIPR antibody (hGIPR-Ab) and found that weight loss was more pronounced than in mice. In addition, we observed enhanced weight loss in DIO mice and NHPs when anti-GIPR antibodies were codosed with glucagon-like peptide-1 receptor (GLP-1R) agonists. Mechanistic and crystallographic studies demonstrated that hGIPR-Ab displaced GIP and bound to GIPR using the same conserved hydrophobic residues as GIP. Further, using a conditional knockout mouse model, we excluded the role of GIPR in pancreatic β-cells in the regulation of body weight and response to GIPR antagonism. In conclusion, these data provide preclinical validation of a therapeutic approach to treat obesity with anti-GIPR antibodies.

Disruption of the murine intestinal alkaline phosphatase gene Akp3 impairs lipid transcytosis and induces visceral fat accumulation and hepatic steatosis

2007 ◽  
Vol 292 (5) ◽  
pp. G1439-G1449 ◽  
Author(s):  
Takanari Nakano ◽  
Ikuo Inoue ◽  
Iwao Koyama ◽  
Kenta Kanazawa ◽  
Koh-ichi Nakamura ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Body Weight ◽  
Weight Gain ◽  
Visceral Fat ◽  
Corn Oil ◽  
Body Weight Gain ◽  
Lipid Absorption ◽  
Wild Type ◽  
Intestinal Alkaline Phosphatase ◽  
Visceral Fat Accumulation

Intestinal alkaline phosphatase (IAP) is involved in the process of fat absorption, a conclusion confirmed by an altered lipid transport and a faster body weight gain from 10 to 30 wk in both male and female mice with a homozygous null mutation of the IAP coding gene ( Akp3−/− mice). This study was aimed to delineate morphologically and quantitatively the accelerated lipid absorption in male Akp3−/− mice. Feeding a corn oil bolus produced an earlier peak of triacylglycerol in serum (2 vs. 4 h for Akp3−/− and wild-type mice, respectively) and an approximately twofold increase in serum triacylglycerol concentration in Akp3−/− mice injected with a lipolysis inhibitor, Triton WR-1339. A corn oil load induced the threefold enlargement of the Golgi vacuoles in male wild-type mice but not in Akp3−/− mice, indicating that absorbed lipids rarely reached the Golgi complex and that the transcytosis of lipid droplets does not follow the normal pathway in male Akp3−/− mice. Force feeding an exaggerated fat intake by a 30% fat chow for 10 wk induced obesity in both male Akp3−/− and wild-type mice, and therefore no phenotypic difference was observed between the two. On the other hand, the forced high-fat chow induced an 18% greater body weight gain, hepatic steatosis, and visceral fat accumulation in female Akp3−/− mice but not in female wild-type controls. These results provide further evidence that IAP is involved in the regulation of the lipid absorption process and that its absence leads to progressive metabolic abnormalities in certain fat-forced conditions.

scholarly journals The Vitamin D Receptor in Osteoblast-Lineage Cells Is Essential for the Proresorptive Activity of 1α,25(OH)2D3 In Vivo

Endocrinology ◽  
2020 ◽  
Vol 161 (11) ◽  
Author(s):  
Tomoki Mori ◽  
Kanji Horibe ◽  
Masanori Koide ◽  
Shunsuke Uehara ◽  
Yoko Yamamoto ◽  
...  
Keyword(s):  
Vitamin D ◽  
Body Weight ◽  
Bone Resorption ◽  
Vitamin D Receptor ◽  
The Body ◽  
Conditional Knockout ◽  
High Dose ◽  
Type I ◽  
Wild Type ◽  
Osteoblast Lineage

Abstract We previously reported that daily administration of a pharmacological dose of eldecalcitol, an analog of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], increased bone mass by suppressing bone resorption. These antiresorptive effects were found to be mediated by the vitamin D receptor (VDR) in osteoblast-lineage cells. Using osteoblast-lineage-specific VDR conditional knockout (Ob-VDR-cKO) mice, we examined whether proresorptive activity induced by the high-dose 1α,25(OH)2D3 was also mediated by VDR in osteoblast-lineage cells. Administration of 1α,25(OH)2D3 (5 μg/kg body weight/day) to wild-type mice for 4 days increased the number of osteoclasts in bone and serum concentrations of C-terminal crosslinked telopeptide of type I collagen (CTX-I, a bone resorption marker). The stimulation of bone resorption was concomitant with the increase in serum calcium (Ca) and fibroblast growth factor 23 (FGF23) levels, and decrease in body weight. This suggests that a toxic dose of 1α,25(OH)2D3 can induce bone resorption and hypercalcemia. In contrast, pretreatment of wild-type mice with neutralizing anti-receptor activator of NF-κB ligand (RANKL) antibody inhibited the 1α,25(OH)2D3-induced increase of osteoclast numbers in bone, and increase of CTX-I, Ca, and FGF23 levels in serum. The pretreatment with anti-RANKL antibody also inhibited the 1α,25(OH)2D3-induced decrease in body weight. Consistent with observations in mice conditioned with anti-RANKL antibody, the high-dose administration of 1α,25(OH)2D3 to Ob-VDR-cKO mice failed to significantly increase bone osteoclast numbers, serum CTX-I, Ca, or FGF23 levels, and failed to reduce the body weight. Taken together, this study demonstrated that the proresorptive, hypercalcemic, and toxic actions of high-dose 1α,25(OH)2D3 are mediated by VDR in osteoblast-lineage cells.

scholarly journals Loss of Maternal microRNA Miogenesis Impairs Gut Health in Wild-Type Pups Fostered to Dicer Knockout Dams

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1113-1113
Author(s):  
Fang Zhou ◽  
Janos Zempleni
Keyword(s):  
Barrier Function ◽  
Cell Communication ◽  
Gut Health ◽  
Wild Type ◽  
Gut Barrier ◽  
Microrna Biogenesis ◽  
Funding Sources ◽  
Gut Barrier Function ◽  
Gates Foundation ◽  
Quality Of Milk

Abstract Objectives Exosomes play a role in cell-to-cell communication, which is achieved by the transfer of microRNAs from donor cells to recipient cells. Exosomes and their microRNA cargos may also be absorbed from milk and accumulate primarily in the intestinal mucosa, kidneys and brains in C57BL/6 pups. MicroRNA biogenesis depends on the endonuclease Dicer, and homozygous Dicer KO is lethal. We hypothesized maternal microRNA biogenesis would be important for optimal postnatal development of pups. This study aimed to assess whether maternal loss of microRNA biogenesis impairs the nutritional quality of milk and gut health in wild-type (WT) pups fostered to Dicer knockout (KO) dams. Methods WT C57BL/6 pups were fostered to tamoxifen-inducible heterozygous Dicer KO dams from synchronized pregnancies (4 pups/dam). In the treatment group, one allele of Dicer was knockout out in dams by i.p. tamoxifen injection after delivery (denoted “Dicer KO”); control dams were injected with vehicle (denoted “CTRL”). Milk was collected 11 days postpartum for analysis of exosomal microRNAs (RT-qPCR), lactose (enzymatic), total protein (BCA assay), total triglycerides (Vitros 250 Analyzer) and water (weighing oven). Postnatal gut morphology and gut barrier function were assessed by histology analysis and oral FITC-dextran at age 3 weeks. The unpaired t-test was used for statistical analysis; P &lt; 0.05 was considered statistically significant. Results The expression of microRNAs in exosomes decreased by 60% in Dicer KO dams compared to CTRL. The loss of maternal microRNA biogenesis impaired gut health in WT pups: 1) The length of the gastrointestinal tract and the width of jejunum decreased by more than 33% and 41% in WT pups fostered to Dicer KO dams, respectively, compared to pups fostered to CTRL. 2) The villi height decreased by 20% (female) and 10% (male) in WT pups fostered Dicer KO dams compared to pups fostered to CTRL. 3) Gut barrier function was impaired, as evidenced by a peak FITC-dextran plasma concentration that was 59% higher in pups fostered to Dicer KO compared to CTRL after oral FITC-dextran. Dicer KO had no effect on the content of macronutrients and water in milk. Conclusions MicroRNAs in milk play a role in optimal postnatal gut health during lactation. Funding Sources NIFA, NIH, Gates Foundation and USDA. J.Z. is a consultant for PureTech Health.

Histamine H1 receptors mediate the anorectic action of the pancreatic hormone amylin

2001 ◽  
Vol 281 (5) ◽  
pp. R1442-R1448 ◽  
Author(s):  
A. Mollet ◽  
T. A. Lutz ◽  
S. Meier ◽  
T. Riediger ◽  
P. A. Rushing ◽  
...  
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Suppressive Effect ◽  
Wild Type ◽  
Histaminergic System ◽  
Endogenous Histamine ◽  
Anorectic Effect ◽  
Histamine H1 Receptors ◽  
Pancreatic Hormone

We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperitoneally injected amylin (5 and 20 μg/kg), the amylin agonist salmon calcitonin (sCT; 10 μg/kg), leptin (1.3 mg/kg), and cholecystokinin (CCK; 20 μg/kg). The experiments were performed with mice lacking functional H1 receptors (H1Rko) and wild-type (WT) controls. The mice were also injected with the H3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through presynaptic H3 receptors. The feeding-suppressive effect of thioperamide was abolished in H1Rko mice. The anorectic effects of amylin and sCT were significantly reduced in 12-h food-deprived H1Rko mice compared with WT mice [1-h food intake: WT-NaCl 0.51 ± 0.05 g vs. WT-amylin (5 μg/kg) 0.30 ± 0.06 g ( P < 0.01); H1Rko-NaCl 0.45 ± 0.05 g vs. H1Rko-amylin 0.40 ± 0.04 g; WT-NaCl 0.40 ± 0.09 g vs. WT-sCT (10 μg/kg) 0.14 ± 0.10 g ( P < 0.05); H1Rko-NaCl 0.44 ± 0.08 g vs. H1Rko-sCT 0.50 ± 0.06 g]. The anorectic effect of leptin was absent in ad libitum-fed H1Rko mice, whereas CCK equally reduced feeding in WT and H1Rko animals. This suggests that the histaminergic system is involved in mediating the anorectic effects of peripheral amylin and sCT via histamine H1 receptors. The same applies to leptin but not to CCK. H1Rko mice showed significantly increased body weight gain compared with WT mice, supporting the role of endogenous histamine in the regulation of feeding and body weight.

scholarly journals EFFECT OF ARTEMISIA SPLENDENS POWDER AND EXTRACT ON BROILER CHICKEN’S PERFORMANCE, LYMPHOID ORGAN WEIGHT, GUT MORPHOLOGY AND SERUM BIOCHEMICALS DURING COCCIDIOSIS CHALLENGE.

2020 ◽  
Vol 51 (2) ◽  
pp. 611-618
Author(s):  
Abdullah & Al-Barwary
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Positive Control ◽  
Negative Control ◽  
Conversion Ratio ◽  
Feed Conversion Ratio ◽  
Gut Health ◽  
Feed Conversion ◽  
Villous Height

The objective of this study was to investigate the efficacy of Artemisia splendens on performance, some serum biochemicals content, lymphoid organs and gut health of broiler chickens challenged with coccidia. This study was conducted at university of Duhok, college of agriculture. A total of 200 day-old Ross 308 chicks were assigned in to 5 treatments (4 replicates pens of 10 birds/pen): unchallenged control (negative control); challenged control (positive control); challenged supplemented with salinomycin in feed  (anticoccidial); challenged supplemented with Artemisia splendens  in drinking water (AS1) and challenged supplemented with Artemisia splendens in feed (AS2). On day 9, challenged birds were inoculated with 5000 sporulated oocysts of Eimeria. The results showed that on day 24, challenged birds in negative control, anticoccidial AS1 and AS2 had higher weight gain and feed conversion ratio compared to positive control. No significant differences were detected between Birds in AS1, AS2 Anticoccidial and negative control for body weight gain and feed conversion ratio. On day 35, birds in AS1 as negative control and anticoccidial groups had higher (P<0.01) body weight gain and feed conversion ration compared to positive control. Negative control, anticoccidial, AS1 and AS2 birds significantly increased villous height and villous height/crypt depth and decreased crept depth when compared to positive control at day 24. The serum globulin concentration of AS1 birds was significantly higher than birds in negative control, positive control and anticoccidial. In conclusion, these results demonstrated the protective effects of Artemisia splendens against performance during coccidiosis challenge.

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