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Obesity, mouse, mice

Anna C Pfalzer, Jimmy W Crott, Gar Yee Koh, Donald E Smith, Paloma E Garcia, Joel B Mason
Obesity is a prominent risk factor for colorectal cancer (CRC). One mechanism by which obesity promotes the development of CRC is by generating a chronic, low-grade state of colonic inflammation. Interleukin-1β (IL-1β), a proinflammatory cytokine often elevated in obesity, is known to activate several procarcinogenic signaling pathways that are implicated in colonic carcinogenesis. We therefore sought to define the role of IL-1β in mediating some of the early biochemical and molecular events leading up to obesity-promoted CRC...
October 2018: Journal of Interferon & Cytokine Research
Daniela Gentile, Matteo Fornai, Carolina Pellegrini, Rocchina Colucci, Laura Benvenuti, Emiliano Duranti, Stefano Masi, Sara Carpi, Paola Nieri, Anna Nericcio, Francesca Garelli, Agostino Virdis, Laura Pistelli, Corrado Blandizzi, Luca Antonioli
Purpose: Luteolin exerts beneficial effects against obesity-associated comorbidities, although its influence on vascular dysfunction remains undetermined. We examined the effects of luteolin on endothelial dysfunction in a mouse model of diet-induced obesity. Methods: Standard diet (SD) or high-fat diet (HFD)-fed mice were treated daily with luteolin intragastrically. After 8 weeks, body and epididymal fat weight, as well as blood cholesterol, glucose, and triglycerides were evaluated. Endothelium-dependent relaxations of resistance mesenteric vessels was assessed by a concentration-response curve to acetylcholine, repeated upon Nw -nitro-L-arginine methylester (L-NAME) or ascorbic acid infusion to investigate the influence of nitric oxide (NO) availability and reactive oxygen species (ROS) on endothelial function, respectively...
2018: Frontiers in Pharmacology
Lin Wang, Liyuan Chen, Zheran Liu, Yaofang Liu, Mao Luo, Ni Chen, Xin Deng, Yulin Luo, Jing He, Liping Zhang, Michael A Hill, Rong Li, Jianbo Wu
Background: Plasminogen activator inhibitor (PAI)-1 levels and activity are known to increase during metabolic syndrome and obesity. In addition, previous studies have implicated PAI-1 in adipose tissue (AT) expansion while also contributing to insulin resistance. As inflammation is also known to occur in AT during obesity, we hypothesized that in a high-fat diet (HFD)-induced obese mouse model PAI-1 contributes to macrophage-mediated inflammation and metabolic dysfunction. Methods: Four- to five-weeks-old male C57B6/6J mice were fed a HFD (45%) for 14 weeks, while age-matched control mice were fed a standard laboratory chow diet (10% fat)...
2018: Frontiers in Pharmacology
Ziye Xu, Wenjing You, Fengqin Wang, Yizhen Wang, Tizhong Shan
Adipose tissues, function as energy metabolism and endocrine organ, are closely associated with metabolic diseases such as obesity, insulin resistance and diabetes. Liver kinase B1 (Lkb1) and mechanistic target of rapamycin (mTOR) play crucial roles in regulating energy metabolism and cell growth in adipose tissue. Our recent study generated an adipocyte-specific Lkb1 and mTOR double knockout (DKO) mouse model and found that DKO of Lkb1 and mTOR caused reduction of brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) mass but increase of liver mass...
October 14, 2018: Adipocyte
Jeong Yoon Chang, Joo Hyun Park, Sung Eun Park, Jinyoung Shon, Yoon Jung Park
OBJECTIVE: Genetic variants at the fat mass- and obesity-associated (FTO) locus are strongly associated with obesity-related traits by regulating neighboring genes. Nevertheless, it is possible that FTO protein is directly involved in mechanisms regulating body composition and adiposity. Here, the in vivo biological functions of FTO in the risk for obesity were studied by reviewing murine models. METHODS: The effects of the locus-specific manipulations of the murine Fto gene on metabolic-related phenotypes in genetically modified mouse models were reviewed and summarized into the following three categories: growth and body composition, eating behaviors, and metabolic homeostasis...
October 12, 2018: Obesity
Adeline N Boettcher, Joan E Cunnick, Ellis J Powell, Timothy K Egner, Sara E Charley, Crystal L Loving, Christopher K Tuggle
BACKGROUND: Severe combined immunodeficient (SCID) pigs are an emerging animal model being developed for biomedical and regenerative medicine research. SCID pigs can successfully engraft human-induced pluripotent stem cells and cancer cell lines. The development of a humanized SCID pig through xenotransplantation of human hematopoietic stem cells (HSCs) would be a further demonstration of the value of such a large animal SCID model. Xenotransplantation success with HSCs into non-obese diabetic (NOD)-derived SCID mice is dependent on the ability of NOD mouse signal regulatory protein alpha (SIRPA) to bind human CD47, inducing higher phagocytic tolerance than other mouse strains...
October 12, 2018: Xenotransplantation
Keiichiro Kamura, Jihoon Shin, Hiroshi Kiyonari, Takaya Abe, Go Shioi, Atsunori Fukuhara, Hiroshi Sasaki
Obesity is characterized by an expansion of white adipose tissue (WAT) mass, which mainly consists of adipocytes. During the commitment and differentiation of adipocytes, PPARγ functions as a key transcriptional factor for adipogenesis, and is associated with its suppressive coregulator, TAZ. Previous studies have shown the importance of TAZ in adipogenesis using an in vitro model; however, the understanding of its role in adipogenesis in vivo remains limited. Here, we report a unique obese mouse model that is associated with TAZ downregulation, which arose from the overexpression of Yap, a Taz paralog...
October 9, 2018: Biochemical and Biophysical Research Communications
Zhijian Zhang, Xing Liu, Huanbai Xu, Xiaoyun Feng, Yi Lin, Yunhong Huang, Yongde Peng, Mingyu Gu
OBJECTIVE: Obesity is associated with an increased risk of many metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain poorly understood. Recent studies have demonstrated that MicroRNA-mediated gene silencing plays an important role in hepatic triglyceride (TG) metabolism. In the present study, we aimed to investigate the pathological function of miR-361-5p in the development of NAFLD. METHODS: Expression levels of miR-361-5p was determined by quantitative real-time PCR in livers of obese mice and NAFLD patients...
November 2018: Metabolism: Clinical and Experimental
Xugang Wang, Rong Huang, Lichen Zhang, Saichao Li, Jing Luo, Yanrong Gu, Zhijun Chen, Qianqian Zheng, Tianzhu Chao, Wenping Zheng, Xinhui Qi, Li Wang, Yinhang Wen, Yinming Liang, Liaoxun Lu
Atherosclerosis is a complex disease affecting arterial blood vessels and blood flow that could result in a variety of life-threatening consequences. Disease models with diverged genomes are necessary for understanding the genetic architecture of this complex disease. Non-obese diabetic (NOD) mice are highly polymorphic and widely used for studies of type 1 diabetes and autoimmunity. Understanding atherosclerosis development in the NOD strain is of particular interest as human atherosclerosis on the diabetic and autoimmune background has not been successfully modeled...
October 8, 2018: Disease Models & Mechanisms
Lei Liu, Ningning Wang, Yanan Ma, Yang Liu, Deliang Wen
Obesity is a severe public health problem worldwide. Our study aims to assess whether a saponin-enriched extract from the leaves of Boussingaultia gracilis (SBG) could attenuate obesity and its related metabolic disorders in mice and to explore the potential mechanism of this effect. Three-week old male mice were fed with a HFD for 7 weeks followed by a 10-week period in which the mice were supplemented with distilled water or SBG (250 mg per kg bodyweight). We demonstrated that SBG supplementation for 10 weeks mitigated obesity and its complications in diet-induced obesity (DIO) mice, such as reducing the hepatic damage underlying steatosis, modulating lipid metabolism, enhancing adipocyte thermogenesis, restoring insulin sensitivity and glucose homeostasis, and alleviating inflammation status...
October 10, 2018: Food & Function
Tae Hyun Kim, Yoon Mee Yang, Chang Yeob Han, Ja Hyun Koo, Hyunhee Oh, Su Sung Kim, Byoung Hoon You, Young Hee Choi, Tae-Sik Park, Chang Ho Lee, Hitoshi Kurose, Mazen Noureddin, Ekihiro Seki, Yu-Jui Yvonne Wan, Cheol Soo Choi, Sang Geon Kim
Non-alcoholic fatty liver disease (NAFLD) arises from mitochondrial dysfunction under sustained imbalance between energy intake and expenditure, but the underlying mechanisms controlling mitochondrial respiration have not been entirely understood. Heterotrimeric G proteins converge signals from activated GPCRs, and modulate cell signaling pathways to maintain metabolic homeostasis. Here, we investigated the regulatory role of Gα12 on hepatic lipid metabolism and whole-body energy expenditure in mice. Fasting increased Gα12 level in mouse liver...
October 9, 2018: Journal of Clinical Investigation
Siying Wei, Jingyu Zhao, Shuo Wang, Meiqin Huang, Yining Wang, Yan Chen
Continuous deficiency of leucine, a member of branched chain amino acids, is able to reduce obesity and improve insulin sensitivity in mice. Intermittent fasting has been shown to be effective in intervention of metabolic disorders including diabetes. However, it is unknown whether intermittent leucine deprivation can intervene in type 2 diabetes progression. We administered leucine-deprived food every other day in db/db mice, a type 2 diabetes model, for a total of eight weeks to investigate the interventional effect of intermittent leucine deprivation...
September 2018: Heliyon
Valerie Mills, Jasmine F Plows, Huan Zhao, Charlotte Oyston, Mark H Vickers, Philip N Baker, Joanna L Stanley
Fetal growth restriction (FGR) is associated with an increased risk of hypertension, insulin resistance, obesity and cardiovascular disease in adulthood. Currently there are no effective treatments to reverse the course of FGR. This study used the eNOS knockout mouse (eNOS-/- ), a model of FGR, to determine the ability of sildenafil, a potential new treatment for FGR, to improve cardiovascular and metabolic outcomes in adult offspring following a complicated pregnancy. Pregnant eNOS-/- and C57BL/6J control dams were randomised to sildenafil treatment (0...
October 5, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Tina Nitezki, Burkhard Kleuser, Stephanie Krämer
This case report addresses the problem of underreporting negative results and adverse side effects in animal testing. We present our findings regarding a hyperphagic mouse model associated with unforeseen high mortality. The results outline the necessity of reporting detailed information in the literature to avoid duplication. Obese mouse models are essential in the study of obesity, metabolic syndrome and diabetes mellitus. An experimental model of obesity can be induced by the administration of gold thioglucose (GTG)...
October 5, 2018: Laboratory Animals
Salman Azhar, Stefanie Bittner, Jie Hu, Wen-Jun Shen, Yuan Cortez, Xiao Hao, Han Lu, Jens O Lagerstedt, Fredric B Kraemer, Jan O Johansson
Previously, apoE-derived ABCA1 agonist peptides have been shown to possess anti-atherosclerotic and possibly antidiabetic properties. Here we assessed the in vitro and in vivo actions of a second generation of ABCA1 peptide agonists, CS6253 and T6991-2, on glucose homeostasis. The results show that these two peptides improve glucose tolerance in a prediabetic diet-induced obesity mouse model by enhancing insulin secretion. It was further demonstrated that T6991-2 also improved glucose tolerance in leptin-deficient (ob/ob) mice...
October 2, 2018: Molecular and Cellular Endocrinology
Yukitomo Arao, Katherine J Hamilton, Sydney L Lierz, Kenneth S Korach
OBJECTIVE: Studies using the estrogen receptor alpha (ERα) knock-out (αERKO) mice have demonstrated that ERα plays a crucial role in various estrogen-mediated metabolic regulations. ERα is a ligand dependent transcription regulator and its activity is regulated by estrogenic compounds. ERα consists of two transcriptional activation domains, AF-1 and AF-2. The activities of these domains are regulated through different mechanisms; however, the specific physiological role in metabolic regulation by these domains is still unclear...
September 20, 2018: Molecular Metabolism
Gwenaëlle Le Menn, Brigitte Sibille, Joseph Murdaca, Anne-Sophie Rousseau, Raphaëlle Squillace, Bastien Vergoni, Mireille Cormont, Isabelle Niot, Paul A Grimaldi, Isabelle Mothe-Satney, Jaap G Neels
The implication of αβ and γδ T cells in obesity-associated inflammation and insulin resistance (IR) remains uncertain. Mice lacking γδ T cells show either no difference or a decrease in high-fat diet (HFD)-induced IR, whereas partial depletion in γδ T cells does not protect from HFD-induced IR. αβ T-cell deficiency leads to a decrease in white adipose tissue (WAT) inflammation and IR without weight change, but partial depletion of these cells has not been studied. We previously described a mouse model overexpressing peroxisome proliferator-activated receptor β (PPAR-β) specifically in T cells [transgenic (Tg) T-PPAR-β] that exhibits a partial depletion in αβ T cells and no change in γδ T-cell number...
October 4, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Xiaoling Jin, Teresa A Zimmers, Zongxiu Zhang, Leonidas G Koniaris
INTRODUCTION: Loss of hepatic epidermal growth factor receptor (EGFR) expression is a cause for the increased perioperative risk for complications and death in patients with obesity and fatty liver undergoing liver resection. Herein, we set out to identify agents that might increase EGFR expression and improve recovery for patients with fatty liver undergoing resection. Using the diet-induced obese (DIO) mouse model of fatty liver, we examined resveratrol as a therapy to induce EGFR expression and improve outcomes following 80% partial hepatectomy (PH) in a murine model...
October 3, 2018: Digestive Diseases and Sciences
Takao Nammo, Haruhide Udagawa, Nobuaki Funahashi, Miho Kawaguchi, Takashi Uebanso, Masaki Hiramoto, Wataru Nishimura, Kazuki Yasuda
AIMS/HYPOTHESIS: Epigenetic regulation of gene expression has been implicated in the pathogenesis of obesity and type 2 diabetes. However, detailed information, such as key transcription factors in pancreatic beta cells that mediate environmental effects, is not yet available. METHODS: To analyse genome-wide cis-regulatory profiles and transcriptome of pancreatic islets derived from a diet-induced obesity (DIO) mouse model, we conducted chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) of histone H3 lysine 27 acetylation (histone H3K27ac) and high-throughput RNA sequencing...
October 3, 2018: Diabetologia
Jenny E Kanter, Leela Goodspeed, Shari Wang, Farah Kramer, Tomasz Wietecha, Diego Gomes-Kjerulf, Savitha Subramanian, Kevin D O'Brien, Laura J den Hartigh
The dietary fatty acid 10,12 conjugated linoleic acid (10,12 CLA) promotes weight loss by increasing fat oxidation, but its effects on atherosclerosis are less clear. We recently showed that weight loss induced by 10,12 CLA in an atherosclerosis-susceptible mouse model with characteristics similar to human metabolic syndrome is accompanied by accumulation of alternatively activated macrophages within subcutaneous adipose tissue. The objective of this study was to evaluate whether 10,12 CLA-mediated weight loss was associated with an atheroprotective phenotype...
October 3, 2018: Nutrients
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