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Obesity, mice

Itay Ayalon, Hui Shen, Lauren Williamson, Keith Stringer, Basilia Zingarelli, Jennifer M Kaplan
Severe sepsis and septic shock are the biggest cause of mortality in critically ill patients. Obesity today is one of the world's greatest health challenges. Little is known about the extent of involvement of the white adipose tissue (WAT) in sepsis and how it is being modified by obesity. We sought to explore the involvement of the WAT in sepsis. We hypothesize that sepsis induces browning of the WAT and that obesity alters the response of WAT to sepsis. Six-week-old C57BL/6 mice were randomized to a high-fat diet to induce obesity (obese group) or control diet (nonobese group)...
November 2018: Shock
Hezhongrong Nie, Xiaohong Yu, Haihong He, Lintao Zhou, Qing Li, Chunli Song, Damin Wang, Tingyu Ren, Zeyan Chen, Hanlian Huang, Xiaoyan Dai, Yiwen Zhou
Emerging evidence suggests that microRNAs (miRNAs) are essential for metabolic haemostasis of liver tissues. Among them, miR-33a is supposed to modulate the cholesterol export and fatty acid oxidation, but whether miR-33a involves in the process of fatty liver disease is unclear. To disclose the hypothesis, we utilized miR-33a mimic and antisense to explore their effects in primary hepatocytes or high-fat diet (HFD)-fed mice. Treatment with palmitic acid (PA) or HFD significantly increased the expression of miR-33a in hepatocytes or liver tissues...
October 16, 2018: Journal of Cellular and Molecular Medicine
Ludivine Coudière Morrison, Nazanin Tatari, Tamra E Werbowetski-Ogilvie
Utilization of human embryonic stem cells (hESCs) as a model system to study highly malignant pediatric cancers has led to significant insight into the molecular mechanisms governing tumor progression and has revealed novel therapeutic targets for these devastating diseases. Here, we describe a method for generating heterogeneous populations of neural precursors from both normal and neoplastic hESCs and the subsequent injection of neoplastic human embryonic neural cells (hENs) into intracerebellar or intracranial xenograft models...
2019: Methods in Molecular Biology
Xinhui Wang, Hong Gao, Wenhui Wu, Enjun Xie, Yingying Yu, Xuyan He, Jin Li, Wanru Zheng, Xudong Wang, Xizhi Cao, Zhuoxian Meng, Ligong Chen, Junxia Min, Fudi Wang
Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly down-regulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover, β-cell-specific Slc39a5 knockout mice have impaired insulin secretion...
October 15, 2018: Protein & Cell
Pijun Yan, Yong Xu, Zhihong Zhang, Chenlin Gao, Jianhua Zhu, Hua Li, Qin Wan
Neuregulin-4 (Nrg4) is a novel adipokine associated with obesity, hyperglycemia, insulin resistance, dislipidemia, inflammation, and oxidative stress in mice and humans. However, no report has demonstrated the relationship of circulating Nrg4 with diabetic peripheral neuropathy (DPN). The objective of our study was to investigate the relationship between circulating Nrg4 and DPN in a cross-sectional study. Circulating Nrg4 levels were determined with an enzyme-linked immunosorbent assays kit in 132 newly diagnosed type 2 diabetes mellitus (nT2DM) patients and 41 normal controls (NC group)...
October 12, 2018: Cytokine
Qin Wang, Yue Yin, Weizhen Zhang
Obese mice demonstrate disruption of the circadian clock and feeding cycle. Circulating ghrelin, a hormone secreted mainly by gastric X/Alike cells, is significantly reduced in obese humans and animals. Here, we examined whether ghrelin improves the disruption of the circadian rhythm in steatotic hepatocytes and liver. The effects of ghrelin on hepatic circadian clock genes were studied in steatotic hepatocytes and liver of mice fed a high-fat diet (HFD) for 12 weeks. The circadian clock of cultured hepatocytes was synchronized by treatment with 100 nM dexamethasone for 1 h...
October 12, 2018: International Journal of Molecular Sciences
Sherry Zhang, Chunxia Lu, Arun K Das, Anil K Pasupulati, Ram K Menon
OBJECTIVE: To investigate the effects of GH signaling on Kupffer cells and the resulting changes in lipid homeostasis and their underlying mechanism(s) in the livers of diet-induced obese (DIO) mice. DESIGN: Male macrophage specific-growth hormone receptor knockout mice (MacGHR KO) and their litter mate controls were fed a high fat diet containing 60% calories from fat for 26 weeks. Lipid content and lipid profiles in the liver and circulation were analyzed. Expression levels of CD36 in the liver were quantified by RT-PCR and Western Blot...
October 4, 2018: Growth Hormone & IGF Research
F Echeverría, R Valenzuela, A Espinosa, A Bustamante, D Álvarez, D Gonzalez-Mañan, M Ortiz, S A Soto-Alarcon, L A Videla
High-fat diet (HFD)-fed mice show obesity with development of liver steatosis and a proinflammatory state without establishing an inflammatory reaction. The aim of this work was to assess the hypothesis that eicosapentaenoic acid (EPA) plus hydroxytyrosol (HT) supplementation prevents the inflammatory reaction through enhancement in the hepatic resolvin content in HFD-fed mice. Male C57BL/6J mice were fed an HFD or a control diet and supplemented with EPA (50 mg/kg/day) and HT (5 mg/kg/day) or their respective vehicles for 12 weeks...
September 21, 2018: Journal of Nutritional Biochemistry
Małgorzata M Dobrzyńska, Aneta Gajowik, Ewa A Jankowska-Steifer, Joanna Radzikowska, Ewa J Tyrkiel
Exposure to environmental toxicants may affect reproduction and development of subsequent generations. This study was aimed at determining the male-mediated F1 effects induced following 8-weeks of subchronic exposure of F0 male mice to bisphenol A (BPA) alone and in a combination with X-rays irradiation (IR) started during their puberty. 4.5 weeks old F0 male mice were exposed to BPA dissolved in ethyl alcohol and diluted in drinking water at the following doses: 5 mg/kg bw, 10 mg/kg bw, 20 mg/kg bw or irradiated with X-rays (0...
October 12, 2018: Toxicology
Muhammad Umair Ijaz, Muhammad Ijaz Ahmed, Xiaoyou Zou, Muzahir Hussain, Min Zhang, Fan Zhao, Xinglian Xu, Guanghong Zhou, Chunbao Li
Consumption of dietary protein at recommended levels is considered a potential strategy to promote satiety and weight management, but how protein from different dietary sources effect the obesity development, lipid metabolism, and gut microbiota is not known. This study focused on the effects of beef, casein, and soy protein diet on lipid metabolism, triglycerides accumulation, and microbial diversity in colon of C57BL/6J mice, which were given either low-fat diets (LFD, 12% Kcal) or high-fat diets (HFD, 60% Kcal) for 12 weeks...
2018: Frontiers in Microbiology
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
Jing Han, Yang Tang, Mingjian Lu, Haiqing Hua
Background: Methionine aminopeptidase 2 (MetAP2) cleaves the initiator methionine from nascent peptides during translation. In both preclinical and clinical studies, the pharmacological inhibition of MetAP2 in obese subjects results in the suppression of food intake and body weight loss. However, the mechanism of action of body weight loss caused by MetAP2 inhibition remains to be elucidated, and the sites of action by pharmacological MetAP2 inhibition remain unknown. Methods: In the present study, a comprehensive analysis of the MetAP2 expression pattern in mice was performed...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
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
Claudiane Guay, Janine K Kruit, Sophie Rome, Véronique Menoud, Niels L Mulder, Angelika Jurdzinski, Francesca Mancarella, Guido Sebastiani, Alena Donda, Bryan J Gonzalez, Camilla Jandus, Karim Bouzakri, Michel Pinget, Christian Boitard, Pedro Romero, Francesco Dotta, Romano Regazzi
Type 1 diabetes is an autoimmune disease initiated by the invasion of pancreatic islets by immune cells that selectively kill the β cells. We found that rodent and human T lymphocytes release exosomes containing the microRNAs (miRNAs) miR-142-3p, miR-142-5p, and miR-155, which can be transferred in active form to β cells favoring apoptosis. Inactivation of these miRNAs in recipient β cells prevents exosome-mediated apoptosis and protects non-obese diabetic (NOD) mice from diabetes development. Islets from protected NOD mice display higher insulin levels, lower insulitis scores, and reduced inflammation...
October 5, 2018: Cell Metabolism
Emily J Onufer, Shirli Tay, Lauren K Barron, Cathleen M Courtney, Brad W Warner, Jun Guo
Mammalian target of rapamycin complex 1 (mTORC1) is a major regulator of cell growth and proliferation through fuel sensing. Systemic inhibition of mTOR as well as manipulation of its downstream products prevent diet-induced obesity. The purpose of this study was to determine the consequences of intestine-targeted mTORC1 inhibition. To attenuate intestinal mTORC1 activity, Villin-CreER mice were crossed with Raptorflox/flox mice, creating an intestinal-specific Raptor null line (i-Raptor -/-). Mice were fed a high fat diet (HFD) and compositional changes as well as food intake levels were assessed...
October 12, 2018: Biochemical and Biophysical Research Communications
Thiago R Araujo, Joel A da Silva, Jean F Vettorazzi, Israelle N Freitas, Camila Lubaczeuski, Emily A Magalhães, Juliana N Silva, Elane S Ribeiro, Antonio C Boschero, Everardo M Carneiro, Maria L Bonfleur, Rosane Aparecida Ribeiro
Obesity predisposes to glucose intolerance and type 2 diabetes (T2D). This disease is often characterized by insulin resistance, changes in insulin clearance, and β-cell dysfunction. However, studies indicate that, for T2D development, disruptions in glucagon physiology also occur. Herein, we investigated the involvement of glucagon in impaired glycemia control in monosodium glutamate (MSG)-obese mice. Male Swiss mice were subcutaneously injected daily, during the first 5 days after birth, with MSG (4 mg/g body weight [BW]) or saline (1...
October 14, 2018: Journal of Cellular Physiology
Lauren E Hillers, Joseph V D'Amato, Tamara Chamberlin, Gretchen Paderta, Lisa M Arendt
Obese women diagnosed with breast cancer have an increased risk for metastasis, and the underlying mechanisms are not well established. Within the mammary gland, adipose-derived stromal cells (ASCs) are heterogeneous cells with the capacity to differentiate into multiple mesenchymal lineages. To study the effects of obesity on ASCs, mice were fed a control diet (CD) or high-fat diet (HFD) to induce obesity, and ASCs were isolated from the mammary glands of lean and obese mice. We observed that obesity increased ASCs proliferation, decreased differentiation potential, and upregulated expression of α-smooth muscle actin, a marker of activated fibroblasts, compared to ASCs from lean mice...
October 11, 2018: Neoplasia: An International Journal for Oncology Research
Pierre-Gilles Blanchard, Rafael J Moreira, Érique de Castro, Alexandre Caron, Marie Côté, Maynara L Andrade, Tiago E Oliveira, Milene Ortiz-Silva, Albert S Peixoto, France Anne Dias, Yves Gélinas, Renata Guerra-Sá, Yves Deshaies, William T Festuccia
OBJECTIVE: We investigated whether PPARγ modulates adipose tissue BCAA metabolism, and whether this mediates the attenuation of obesity-associated insulin resistance induced by pharmacological PPARγ activation. METHODS: Mice with adipocyte deletion of one or two PPARγ copies fed a chow diet and rats fed either chow, or high fat (HF) or HF supplemented with BCAA (HF/BCAA) diets treated with rosiglitazone (30 or 15 mg/kg/day, 14 days) were evaluated for glucose and BCAA homeostasis...
October 11, 2018: Metabolism: Clinical and Experimental
Huiting Xu, Qiang Fu, Yi Zhou, Chengbin Xue, Patrick Olson, Ernest C Lynch, Ke K Zhang, Chaodong Wu, Peter Murano, Lanjing Zhang, Linglin Xie
Although a pre-pregnancy dietary intervention is believed to be able to prevent offspring obesity, research evidence is absent. We hypothesize that a long period of pre-pregnancy maternal diet transition from a high-fat (HF) diet to a normal-fat (NF) diet effectively prevents offspring obesity, and this preventive effect is independent of maternal body weight change. In our study, female mice were either continued on an NF diet (NF group) or an HF diet (HF group) until weaning, or switched from an HF to an NF for 1 week (H1N group), 5 weeks (H5N group) or 9 weeks (H9N group) before pregnancy...
September 22, 2018: Journal of Nutritional Biochemistry
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