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Obesity, mouse, mice

Eduardo C Alexandre, Fabiano B Calmasini, Amanda C da S Sponton, Mariana G de Oliveira, Diana M André, Fábio H Silva, Maria Andréia Delbin, Fabíola Z Mónica, Edson Antunes
Obese mice display overactive bladder (OAB) associated with impaired urethra smooth muscle (USM) function. In this study, we evaluated the role of the adipose tissue surrounding the urethra and prostate in obese mice (here referred as periprostatic adipose tissue; PPAT) to the USM dysfunction. Male C57BL6/JUnib mice fed with either a standard-chow or high-fat diet to induce obesity were used. In PPAT, histological analysis, and qPCR analysis for gp91phox, tumor necrosis factor-α (TNF-α) and superoxide dismutase (SOD) were conducted...
August 10, 2018: European Journal of Pharmacology
Arnon D Lieber, Ulf H Beier, Haiyan Xiao, Benjamin J Wilkins, Jing Jiao, Xinmin S Li, Rebecca C Schugar, Christopher M Strauch, Zeneng Wang, J Mark Brown, Stanley L Hazen, Nicholas A Bokulich, Kelly V Ruggles, Tatiana Akimova, Wayne W Hancock, Martin J Blaser
Alterations in gut microbiota are known to affect intestinal inflammation and obesity. Antibiotic treatment can affect weight gain by elimination of histone deacetylase (HDAC) inhibitor-producing microbes, which are anti-inflammatory by augmenting regulatory T (Treg ) cells. We asked whether mice that lack HDAC6 and have potent suppressive Treg cells are protected from microbiota-induced accelerated weight gain. We crossed wild-type and HDAC6-deficient mice and subjected the offspring to perinatal penicillin, inducing weight gain via microbiota disturbance...
August 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Laure Monteillet, Monika Gjorgjieva, Marine Silva, Vincent Verzieux, Linda Imikirene, Adeline Duchampt, Hervé Guillou, Gilles Mithieux, Fabienne Rajas
OBJECTIVE: Ectopic lipid accumulation in the liver and kidneys is a hallmark of metabolic diseases leading to non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). Moreover, recent data have highlighted a strong correlation between NAFLD and CKD incidences. In this study, we use two mouse models of hepatic steatosis or CKD, each initiated independently of the other upon the suppression of glucose production specifically in the liver or kidneys, to elucidate the mechanisms underlying the development of CKD in the context of NAFLD-like pathology...
August 1, 2018: Molecular Metabolism
Mami Takahashi, Mika Hori, Rikako Ishigamori, Michihiro Mutoh, Toshio Imai, Hitoshi Nakagama
Obesity, type 2 diabetes mellitus (T2DM) and aging are associated with pancreatic cancer risk, but the mechanisms of pancreatic cancer development caused by these factors are not clearly understood. Syrian golden hamsters are susceptible to N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinogenesis. Aging, BOP treatment and/or a high-fat diet cause severe and scattered fatty infiltration (FI) of the pancreas with abnormal adipokine production and promote pancreatic ductal adenocarcinoma (PDAC) development...
August 12, 2018: Cancer Science
Sung Pyo Hong, Dongoh Han, Ki-Ho Chang, Soon Kil Ahn
11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a cortisol regenerating enzyme that amplifies tissue glucocorticoid levels, especially in the liver and adipose tissue. Knockout mice or a selective inhibitor of 11β-HSD1 improves metabolic syndrome parameters in preclinical models and human clinical trials. Here, we evaluated the therapeutic potential of INU-101, a potent and selective oral inhibitor of 11β-HSD1. The in vitro activity of 11β-HSD1 was measured using the homogeneous time-resolved fluorescence (HTRF) assay...
August 7, 2018: European Journal of Pharmacology
Vivian K Lee, Brett M Hosking, Joanna Holeniewska, Ewa C Kubala, Peter Lundh von Leithner, Peter J Gardner, Richard H Foxton, David T Shima
AIMS/HYPOTHESIS: Diabetic retinopathy is increasing in prevalence worldwide and is fast becoming a global epidemic and a leading cause of visual loss. Current therapies are limited, and the development of effective treatments for diabetic retinopathy requires a greater in-depth knowledge of disease progression and suitable modelling of diabetic retinopathy in animals. The aim of this study was to assess the early pathological changes in retinal morphology and neuronal, inflammatory and vascular features consistent with diabetic retinopathy in the ob/ob mouse model of type 2 diabetes, to investigate whether features similar to those in human diabetic retinopathy were present...
August 9, 2018: Diabetologia
Hiroaki Tanaka, Takenori Yamashita, Misao Yoneda, Satoshi Takagi, Toshihiro Miura
Objective: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia, hyperinsulinemia, and complications such as obesity and osteoporosis. The Tsumura, Suzuki, Obese Diabetes (TSOD) mouse is an animal model of spontaneous obese T2DM. However, bone metabolism in TSOD mice is yet to be investigated. The objective of the present study was to investigate the effects of T2DM on bone mass, metabolism, microstructure, and strength in TSOD mice. Methods: We determined the following parameters in TSOD mice and Tsumura, Suzuki, Non-obesity (TSNO) mice (as controls): serum glucose levels; serum insulin levels; bone mass; bone microstructure; bone metabolic markers; and bone strength...
December 2018: Bone Reports
Julie K Bray, Gabriel S Chiu, Leslie K McNeil, Morgan L Moon, Robyn Wall, Albert E Towers, Gregory G Freund
Background: Reducing caloric intake is a proven intervention for mitigating and modulating morbidities associated with overnutrition. Caloric restriction is difficult to affect clinically, therefore, dietary interventions that ameliorate the adverse consequences of overnutrition in the presence of a high-calorie diet would be of value. Methods: Mice were fed an obesogenic diet containing 60% fat + 10% cellulose (HFC), or a control diet containing 10% fat + 10% cellulose (LFC) for 12 wks...
2018: Nutrition & Metabolism
Mariana G de Oliveira, Daniel M Nascimento, Eduardo C Alexandre, Sandra M Bonilla-Becerra, Adriana Zapparoli, Fabiola Z Mónica, Edson Antunes
AIMS: Overactive bladder (OAB) is one of the most common complications of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). In healthy conditions, menthol infused intravesically reduces the threshold for initiating micturition reflex, but no study evaluated its effects in diabetic conditions. Therefore, we have used mouse models of T1DM and T2DM to evaluate the effects of menthol on cystometric alterations and increased bladder contractility in vitro. METHODS: For T1DM induction, male C57BL6 mice were injected with streptozotocin (STZ) and evaluated after 4 weeks...
August 8, 2018: Neurourology and Urodynamics
Antonia Graja, Francisco Garcia-Carrizo, Anne-Marie Jank, Sabrina Gohlke, Thomas H Ambrosi, Wenke Jonas, Siegfried Ussar, Matthias Kern, Annette Schürmann, Krasimira Aleksandrova, Matthias Blüher, Tim J Schulz
Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well-known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue-resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix-modifying proteins, have been described...
August 7, 2018: Aging Cell
Michael A Cooper, Colin McCoin, Dong Pei, John P Thyfault, Devin Koestler, Douglas E Wright
NEW FINDINGS: What is the central question of this study? Do peripheral sensory neurons metabolize fat-based fuel sources, and does a ketogenic diet modify these processes? What is the main finding and its importance We show that peripheral axons from mice fed a ketogenic diet respond to fat-based fuel sources with reduced respiration and H2 O2 emission compared with mice fed a control diet. These results add to our understanding of the responses of sensory neurons to neuropathy associated with poor diet, obesity and metabolic syndrome...
August 8, 2018: Experimental Physiology
Daniel B Harmon, Chao Wu, Nikolas Dedousis, Ian J Sipula, Maja Stafanovic-Racic, Gabriele Schoiswohl, Christopher P O'Donnell, Laura C Alonso, Erin E Kershaw, Eric E Kelley, Robert M O'Doherty
Accumulation of myeloid cells in the liver, notably dendritic cells (DC) and monocytes/macrophages (MC), is a major component of the metainflammation of obesity. However, the mechanism(s) stimulating hepatic DC/MC infiltration remain ill-defined. Herein, we addressed the hypothesis that adipose tissue (AT) free fatty acids (FFA) play a central role in the initiation of hepatic DC/MC accumulation, using a number of mouse models of altered FFA supply to the liver. In two models of acute FFA elevation (lipid infusion and fasting) hepatic DC/MC and triglycerides (TG), but not AT DC/MC, were increased without altering plasma cytokines (PC; TNFα and MCP-1), and with variable effects on oxidative stress (OxS) markers...
August 7, 2018: American Journal of Physiology. Endocrinology and Metabolism
Daniel Ferguson, Mitchell Blenden, Irina Hutson, Yingqiu Du, Charles A Harris
The global obesity epidemic is fueling alarming rates of diabetes, associated with increased risk of cardiovascular disease and cancer. Leptin is a hormone secreted by adipose tissue that is a key regulator of body weight and energy expenditure. Leptin-deficient humans and mice are obese, diabetic, infertile, and have hepatic steatosis. While leptin replacement therapy can rescue the pathologies seen in leptin-deficient patients and mouse models, treatment is very costly and requires daily injections. Since adipocytes are the source of leptin secretion we investigated whether mouse embryonic fibroblasts (MEFs), capable of forming adipocytes, could be injected into ob/ob mice and prevent the metabolic phenotype seen in these leptin-deficient mice...
July 31, 2018: Endocrinology
Elisa Principi, Ambra Buschiazzo, Andrea Papait, Patrizio Castagnola, Delfina Costa, Roberta Pece, Irena Maric, Mara Scussolini, Cecilia Marini, Gianmario Sambuceti, Felice Strollo, Sara Tavella
BACKGROUND: Lipocalin-2 (LCN2) is widely expressed in the organism with pleiotropic roles. In particular, its overexpression correlates with tissue stress conditions including inflammation, metabolic disorders, chronic diseases and cancer. OBJECTIVES: To assess the effects of systemic LCN2 overexpression on adipose tissue and glucose metabolism. SUBJECTS: Eighteen-month-old transgenic mice with systemic LCN2 overexpression (LCN2-Tg) and age/sex-matched wild-type mice...
August 6, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Luca Antonioli, Valentina Caputi, Matteo Fornai, Carolina Pellegrini, Daniela Gentile, Maria Cecilia Giron, Genny Orso, Nunzia Bernardini, Cristina Segnani, Chiara Ippolito, Balázs Csóka, György Haskó, Zoltán H Németh, Carmelo Scarpignato, Corrado Blandizzi, Rocchina Colucci
BACKGROUND: The murine model of high fat diet (HFD)-induced obesity is characterized by an increment of intestinal permeability, secondary to an impairment of mucosal epithelial barrier and enteric inflammation, followed by morphofunctional rearrangement of the enteric nervous system. The present study investigated the involvement of abdominal macrophages in the mechanisms underlying the development of enteric dysmotility associated with obesity. METHODS: Wild type C57BL/6J mice were fed with HFD (60% kcal from fat) or normocaloric diet (NCD, 18% kcal from fat) for 8 weeks...
August 6, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
S Leon, I Velasco, M J Vázquez, A Barroso, D Beiroa, V Heras, F Ruiz-Pino, M Manfredi-Lozano, A Romero-Ruiz, M A Sanchez-Garrido, C Dieguez, L Pinilla, J Roa, R Nogueiras, M Tena-Sempere
BACKGROUND: RF-amide-related peptide-3 (RFRP-3), the mammalian ortholog of gonadotropin-inhibiting hormone, operates as inhibitory signal for the reproductive axis. Recently, RFRP-3 has been also suggested to stimulate feeding, and therefore might contribute to the control of body weight and its alterations. Yet, characterization of the metabolic actions of RFRP-3 has been so far superficial and mostly pharmacological. Here, we aim to investigate the physiological roles of RFRP-3 signaling in the control of feeding and metabolic homeostasis using a novel mouse model of genetic ablation of its canonical receptor, NPFF1R...
July 31, 2018: Metabolism: Clinical and Experimental
Sarah Just, Stanislas Mondot, Josef Ecker, Katrin Wegner, Eva Rath, Laura Gau, Theresa Streidl, Genevieve Hery-Arnaud, Sinah Schmidt, Till Robin Lesker, Valentin Bieth, Andreas Dunkel, Till Strowig, Thomas Hofmann, Dirk Haller, Gerhard Liebisch, Philippe Gérard, Sascha Rohn, Patricia Lepage, Thomas Clavel
BACKGROUND: As the gut microbiota contributes to metabolic health, it is important to determine specific diet-microbiota interactions that influence host metabolism. Bile acids and dietary fat source can alter phenotypes of diet-induced obesity, but the interplay with intestinal microorganisms is unclear. Here, we investigated metabolic consequences of diets enriched in primary bile acids with or without addition of lard or palm oil, and studied gut microbiota structure and functions in mice...
August 2, 2018: Microbiome
Xiaobing Zhang, Yunfei Song, Yipei Ding, Wei Wang, Ling Liao, Jin Zhong, Pengbo Sun, Fan Lei, Yaou Zhang, Weidong Xie
Obesity and nonalcoholic fatty liver disease (NAFLD) are highly prevalent and cause numerous metabolic diseases. However, drugs for the prevention and treatment of obesity and NAFLD remain unavailable. In this study, we investigated the effects of mogrosides (luo han guo, LH) in Siraitia grosvenorii saponins on high-fat-diet-induced obesity and NAFLD in mice. We found that compared with the negative control, LH reduced body and liver weight. LH also decreased fat accumulation and increased AMP-activated protein kinase (AMPK) phosphorylation (pAMPK) levels in mouse livers...
July 29, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
David Sacerdoti, Shailendra P Singh, Joseph Schragenheim, Lars Bellner, Luca Vanella, Marco Raffaele, Aliza Meissner, Ilana Grant, Gaia Favero, Rita Rezzani, Luigi F Rodella, David Bamshad, Edward Lebovics, Nader G Abraham
Aim: Nonalcoholic steatohepatitis (NASH) is the consequence of insulin resistance, fatty acid accumulation, oxidative stress, and lipotoxicity. We hypothesize that an increase in the inflammatory adipokine NOV decreases antioxidant Heme Oxygenase 1 (HO-1) levels in adipose and hepatic tissue, resulting in the development of NASH in obese mice. Methods: Mice were fed a high fat diet (HFD) and obese animals were administered an HO-1 inducer with or without an inhibitor of HO activity to examine levels of adipose-derived NOV and possible links between increased synthesis of inflammatory adipokines and hepatic pathology...
2018: International Journal of Hepatology
Jarinyaporn Naowaboot, Supaporn Wannasiri, Patchareewan Pannangpetch
Vernonia cinerea (V cinerea) is a plant distributed in grassy areas in Southeast Asia and has several pharmacological effects, including antidiabetic activity. However, the information available regarding the effect of V cinerea on insulin resistance in high-fat diet (HFD)-induced obese mice is not yet determined. We hypothesized that V cinerea water extract (VC) improves insulin sensitivity in HFD-induced obese mice by modulating both phosphatidylinositol-3-kinase (PI3K) and adenosine monophosphate-activated protein kinase (AMPK) pathways in liver, skeletal muscle, and adipose tissue...
August 2018: Nutrition Research
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