217-LB: YH34160, a Novel Long-Acting GDF15 Fusion Protein, Elicits Potent and Sustained Body Weight Loss in Obese Animal Models

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 217-LB
Author(s):  
SEYOUNG LIM ◽  
JIEUN YANG ◽  
DO-HOON KIM ◽  
MI KYEONG JU ◽  
SUKYUNG KIM ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Animal Models ◽  
Fusion Protein ◽  
Body Weight Loss ◽  
Obese Animal ◽  
Long Acting

scholarly journals Effect of mushrooms on obesity in animal models: study protocol for a systematic review and meta-analysis

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Denise Grotto ◽  
Isabella Ferreira Camargo ◽  
Katia Kodaira ◽  
Lauren Giustti Mazzei ◽  
Juliana Castro ◽  
...  
Keyword(s):  
Systematic Review ◽  
Weight Loss ◽  
Body Weight ◽  
Animal Models ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Body Weight Loss ◽  
Preclinical Research ◽  
Medicinal Mushrooms ◽  
Aquatic Mammal

Abstract Background Obesity and its consequences are worldwide epidemic problem; therefore, studies with strategies and mechanisms that favor weight loss to improve outcomes in health are necessary. Effects of mushrooms on body weight are uncertain. The aim of this systematic review is to determine the efficacy of mushrooms in weight loss in animal preclinical models. Method This is a systematic review of preclinical studies of animal models of obesity (any type of non-aquatic mammal), which were exposed to edible and medicinal mushrooms orally in comparison with the control. The following databases will be used: MEDLINE (PubMed), Web of Science, BIOSIS, SCOPUS, and gray literature. There will be no restriction of language, date, or publication status. The primary outcome will be body weight loss. And the secondary outcomes include the total amount of food consumed by the animals, analysis of metabolic parameters, inflammatory mediators, mortality for any causes, and any adverse effect reported. A team of reviewers will select, in pairs and independently, the titles and abstracts, extract data from qualifying studies, and assess bias risk (using SYstematic Review Centre for Laboratory animal Experimentation SYRCLE’s risk of bias tool and the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist). The standardized mean difference (SMD) will be calculated to measure treatment effect, with 95% confidence intervals (95% CI). The heterogeneity between-study will be calculated by I2 inconsistency values and Cochran’s Q statistical test, where I2 > 50% and/or p < 0.10 suggest high heterogeneity meta-analyses of random effects will be conducted as possible. Discussion Although many experimental studies about the effects of mushrooms on obesity have already been published, there is still no consensus in the literature. This study will provide evidences of preclinical research on mushrooms and their relation to body weight loss in animal models of obesity, being non-aquatic mammals. Also, this systematic review will show the limitations and strengths of the studies available in the literature, as well as it will to encourage the financing of new studies by public health managers and governmental entities. Systematic review registration PROSPERO (CRD42019125299).

573 A novel human anti-PD1/IL15 bi-functional protein with robust anti-tumor activity and low systemic toxicity

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A607-A607
Author(s):  
Dan Lu ◽  
Zhanna Polonskaya ◽  
Tzu-Pei Chang ◽  
Stella Martomo ◽  
Xenia Luna ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Weight Loss ◽  
Body Weight ◽  
Fusion Protein ◽  
Body Weight Loss ◽  
Systemic Toxicity ◽  
Wild Type ◽  
Functional Protein ◽  
Bifunctional Protein ◽  
Anti Tumor Activity

BackgroundIL-15 is a key cytokine promoting CD8+ T, NK, and NKT cell proliferation and has demonstrated clinical activity in cancer patients without evidence of any Treg stimulation.1 2 However, its short half-life and systemic toxicity limit its clinical utility. Kadmon has established an IL-15 fusion protein platform to extend the IL-15 serum half-life and direct its action to the tumor microenvironment.3 A major asset of this platform is anti-PD1/IL15 bifunctional protein. To test the bifunctionality hypothesis of this fusion protein in murine models, four different formats of the surrogate bi-functional proteins were engineered by fusing mouse IL-15 to a mouse-human chimeric anti-mouse PD1 antibody (m3A7). We presented earlier that the single IL-15 N-terminal fusion to anti-PD1 antibody (1N-IL-15/m3A7) showed significantly stronger anti-tumor activity in vivo mainly due to the cis-presentation to the PD1 and IL2Rβγ co-expressed on TILs. The cis-presentation potentially maximizes the bi-functionality of PD1 blockade and IL-15 stimulation.4 Here, the therapeutic single IL-15 N-terminal fusion antibodies containing a novel human PD1 antagonist antibody (38B2) and either wild-type IL15 (1N-IL-15/38B2) or mutated 65S-IL15 (65S-1N-IL-15/38B2) have been constructed; their anti-PD1 functions, IL15 stimulation and anti-tumor activities were evaluated.MethodsPurified 1N-IL-15/38B2 and 65S-1N-IL-15/38B2 were generated and characterized in vitro.4 The anti-tumor activities were examined in the human-PD-1/PD-L1 transgenic BALB/c mice subcutaneously transplanted with the human-PD-L1 positive CT26 colon carcinoma. The treatment was started when tumors reached 100 mm3 (IP, QW).ResultsAll 1N-IL-15/anti-PD1 fusions showed similar potencies in binding to the soluble and cell expressed human PD1 and blocking the hPDL-1 binding to hPD1. Comparing to wild-type 1N-IL-15/38B2, mutated 65S-1N-IL-15/38B2 showed lower stimulation (>150 folds) in the M07e, CTLL2, mouse spleen cells and hPBMC (mainly CD8T+ T cell) proliferation. When we treated hPDL1-CT26 tumor transplanted hPDL1-hPD1 transgenic mice with 65S-1N-IL-15/38B2 at 6 mg/kg, 80% of tumor growth inhibition (TGI) was achieved with no body-weight loss. Although wild-type 1N-IL-15/38B2 at 3 mg/kg demonstrated similar efficacy, a significant mouse body-weight loss was observed and 1/3 mice died after second injection. No anti-tumor activity was observed for 65S-1N-IL-15 non-target fusion in 6 mg/kg.ConclusionsThe previous observation of robust anti-tumor activity of surrogate 1N-IL-15/m3A7 in PD1 resistant LL2 model was replicated with the therapeutic bifunctional protein in this study. We also found that lower stimulation 65S-1N-IL-15/38B2 showed strong anti-tumor activity with significant low systemic toxicity; suggesting that the 65S mutation increased the therapeutic window of this bi-functional proteinReferencesGoldrath, AW etc. Cytokine requirements for acute and basal homeostatic proliferation of naive and memory CD8+ T cells. J Exp Med 2002; 195:1515–1522.Waldmann TA. Cytokines in Cancer Immunotherapy. Cold Spring Harb Perspect Biol 2018;103. Martomo, S. etc. ESMO 2019 1221P; SITC 2019 P#4854. Polonskaya Z. etc. AACR 2020 #2263

PGLP‐1, a novel long‐acting dual‐function GLP‐1 analog, ameliorates streptozotocin‐induced hyperglycemia and inhibits body weight loss

2017 ◽  
Vol 31 (8) ◽  
pp. 3527-3539 ◽  
Author(s):  
Huashan Gao ◽  
Qian Zhao ◽  
Ziwei Song ◽  
Zhaocong Yang ◽  
You Wu ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Body Weight Loss ◽  
Dual Function ◽  
Long Acting

109-LB: Potent Weight Loss Mechanism by a Novel Long-Acting Glucagon Analog, HM15136, in Animal Models

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 109-LB
Author(s):  
JONG SUK LEE ◽  
JUNG KUK KIM ◽  
JINYOUNG KIM ◽  
EUNJIN PARK ◽  
SANG HYUN LEE ◽  
...  
Keyword(s):  
Weight Loss ◽  
Animal Models ◽  
Loss Mechanism ◽  
Long Acting

1965-P: Glucagon Receptor Agonism Stimulates Body Weight Loss in Antibiotic Treatment in Obese Mice

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1965-P
Author(s):  
TEAYOUN KIM ◽  
JESSICA P. ANTIPENKO ◽  
SHELLY NASON ◽  
NATALIE PRESEDO ◽  
WILLIAM J. VAN DER POL ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Antibiotic Treatment ◽  
Body Weight Loss ◽  
Obese Mice ◽  
Glucagon Receptor

Relation between change in treatment for central diabetes insipidus and body weight loss

2018 ◽  
Vol 44 (1) ◽  
Author(s):  
Ayako Ito ◽  
Aya Nozaki ◽  
Ichiro Horie ◽  
Takao Ando ◽  
Atsushi Kawakami
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Diabetes Insipidus ◽  
Body Weight Loss ◽  
Central Diabetes Insipidus

scholarly journals Isoquinoline Alkaloids in Sows’ Diet Reduces Body Weight Loss during Lactation and Increases IgG in Colostrum

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2195
Author(s):  
Ester Arévalo Sureda ◽  
Xuemei Zhao ◽  
Valeria Artuso-Ponte ◽  
Sophie-Charlotte Wall ◽  
Bing Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Body Weight ◽  
Body Weight Loss ◽  
Muscle Thickness ◽  
Passive Immunity ◽  
Isoquinoline Alkaloids ◽  
Back Muscle ◽  
Fat Thickness ◽  
And Performance

Isoquinoline alkaloids (IQ) exert beneficial antimicrobial and anti-inflammatory effects in livestock. Therefore, we hypothesized that supplementing sows’ diets with IQ during gestation would decrease farrowing stress, affecting the piglets’ development and performance. Sows were divided into: IQ1, supplemented with IQ from gestation day 80 (G80) to weaning; IQ2, supplemented from gestation day 110 (G110) to weaning, and a non-supplemented (NC) group. Sow body weight (BW), feed intake, back-fat thickness and back-muscle thickness were monitored. Cortisol, glucose and insulin were measured in sows’ blood collected 5 d before, during, and after 7 d farrowing. Protein, fat, IgA and IgG were analyzed in the colostrum and milk. Piglets were monitored for weight and diarrhea score, and for ileum histology and gene expression 5 d post-weaning. IQ-supplemented sows lost less BW during lactation. Glucose and insulin levels were lower in the IQ groups compared to NC-sows 5 d before farrowing and had higher levels of protein and IgG in their colostrum. No other differences were observed in sows, nor in the measured parameters in piglets. In conclusion, IQ supplementation affected sows’ metabolism, reducing body weight loss during lactation. Providing IQ to sows from their entrance into the maternity barn might be sufficient to induce these effects. IQ improved colostrum quality, increasing the protein and IgG content, improving passive immunity for piglets.

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