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Obesity, mice

Alessandra Feraco, Andrea Armani, Riccardo Urbanet, Aurelie Nguyen Dinh Cat, Vincenzo Marzolla, Frederic Jaisser, Massimiliano Caprio
Obesity is a major risk factor that contribute to the development of cardiovascular disease and type 2 diabetes. Mineralocorticoid receptor (MR) expression is increased in the adipose tissue of obese patients and several studies provide evidence that MR pharmacological antagonism improves glucose metabolism in genetic and diet-induced mouse models of obesity. In order to investigate whether the lack of adipocyte MR is sufficient to explain these beneficial metabolic effects, we generated a mouse model with inducible adipocyte-specific deletion of Nr3c2 gene encoding MR (adipo-MRKO)...
August 18, 2018: Journal of Endocrinology
Qinghua Wang, Jing Tang, Shujun Jiang, Zan Huang, Anying Song, Siyuan Hou, Xiang Gao, Hai-Bin Ruan
Peroxisome proliferator-activated receptor-γ (PPARγ) is a master regulator of adipogenesis and a target of the thiazolidinedione (TZD) class of antidiabetic drugs; therefore, identifying novel regulators of PPARγ action in adipocytes is essential for the future development of therapeutics for diabetes. MAGE family member D1 (MAGED1), by acting as an adaptor for ubiquitin-dependent degradation pathways and a co-factor for transcription, plays an important role in neural development, cell differentiation, and circadian rhythm...
August 18, 2018: Journal of Endocrinology
Esther Paulo, Dongmei Wu, Peter A Hecker, Yun Zhang, Biao Wang
Numerous studies have suggested that beige adipocyte abundance is correlated with improved metabolic performance, but direct evidence showing that beige adipocyte expansion protects animals from the development of obesity is missing. Previously, we have described that the Liver kinase b1 (Lkb1) regulates beige adipocyte renaissance in subcutaneous inguinal white adipose tissue (iWAT) through a class IIa histone deacetylase 4 (HDAC4)-dependent mechanism. This study investigates the physiological impact of persistent beige adipocyte renaissance in energy homeostasis in mice...
August 18, 2018: Journal of Endocrinology
Michiyo Takagi, Kazunori Kimura, Ken-Ichi Nakashima, Takao Hirai, Makoto Inoue
The prevalence of obesity and its associated diseases is increasing worldwide, and the therapeutic potential of increasing energy expenditure through differentiation or activation of beige adipocytes has attracted much interest. Therefore, we explored naturally occurring compounds that induce beige adipocytes by screening for activity to induce mRNA expression of uncoupling protein 1 (UCP1) in stromal vascular fraction (SVF) cells cultured in beige adipocyte differentiation medium. Through screening, p-synephrine, a compound isolated from Citrus unshiu Marcov...
August 15, 2018: European Journal of Pharmacology
Eric M Desjardins, Gregory R Steinberg
PURPOSE OF REVIEW: The global prevalence of type 2 diabetes (T2D) is escalating at alarming rates, demanding the development of additional classes of therapeutics to further reduce the burden of disease. Recent studies have indicated that increasing the metabolic activity of brown and beige adipose tissue may represent a novel means to reduce circulating glucose and lipids in people with T2D. The AMP-activated protein kinase (AMPK) is a cellular energy sensor that has recently been demonstrated to be important in potentially regulating the metabolic activity of brown and beige adipose tissue...
August 17, 2018: Current Diabetes Reports
Bernard P Kok, Andrea Galmozzi, Nicole K Littlejohn, Verena Albert, Cristina Godio, Woojoo Kim, Sean M Kim, Jeffrey S Bland, Neile Grayson, Mingliang Fang, Wolfgang Meyerhof, Gary Siuzdak, Supriya Srinivasan, Maik Behrens, Enrique Saez
OBJECTIVES: Extracts of the hops plant have been shown to reduce weight and insulin resistance in rodents and humans, but elucidation of the mechanisms responsible for these benefits has been hindered by the use of heterogeneous hops-derived mixtures. Because hop extracts are used as flavoring agents for their bitter properties, we hypothesized that bitter taste receptors (Tas2rs) could be mediating their beneficial effects in metabolic disease. Studies have shown that exposure of cultured enteroendocrine cells to bitter tastants can stimulate release of hormones, including glucagon-like peptide 1 (GLP-1)...
August 4, 2018: Molecular Metabolism
Michael J Jurczak, Saumya Saini, Simona Ioja, Diana K Costa, Nnamdi Udeh, Xiaojian Zhao, Jean M Whaley, Richard G Kibbey
Inhibition of the sodium-glucose co-transporter type 2 (SGLT2) has received growing acceptance as a novel, safe and effective means to improve glycemic control in patients with type 2 diabetes. Inhibition of SGLT2 lowers the renal glucose threshold and reduces plasma glucose by promoting glucose excretion in urine. Both animal studies and clinical trials in man suggest that SGLT2 inhibition has the potential to improve pancreatic β-cell function by reducing glucose toxicity. However, there is limited data exploring how reducing glucotoxicity via SGLT2 inhibition affects rates of β-cell proliferation and death throughout life in the context of insulin resistance and type 2 diabetes...
August 17, 2018: Islets
Syed S Quadri, Silas Culver, Nrupama Ramkumar, Donald E Kohan, Helmy M Siragy
Recent studies have demonstrated that the renal (pro)renin receptor (PRR) regulates expression of the alpha subunit of the epithelial sodium channel (α-ENaC). In this study we hypothesized that the renal PRR mediates high fat diet (HFD)-induced sodium retention and elevated systolic blood pressure (SBP) by enhancing expression of the epithelial sodium channel (α-ENaC). In our study we used a recently developed inducible nephron specific PRR knockout mouse. Mice (n = 6 each group) were allocated to receive regular diet (RD, 12 kcal% fat) or a high-fat diet (HFD, 45 kcal% fat) for 10 weeks...
2018: PloS One
Ilya R Bederman, Gavriella Pora, Maureen O'Reilly, James Poleman, Kimberly Spoonhower, Michelle Puchowicz, Aura Perez, Bernadette O Erokwu, Alex Rodriguez-Palacios, Chris A Flask, Mitchell L Drumm
Negative energy balance is a prevalent feature of cystic fibrosis (CF). Pancreatic insufficiency, elevated energy expenditure, lung disease, and malnutrition, all characteristic of CF, contribute to the negative energy balance causing low bodily growth phenotype. As low body weight and BMI strongly correlate with poor lung health and survival of CF patients, improving energy balance is an important clinical goal (e.g. high-fat diet). CF mouse models also exhibit negative energy balance (growth retardation and high energy expenditure), independent from exocrine pancreatic insufficiency, lung disease, and malnutrition...
August 17, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Laura J den Hartigh, Leela Goodspeed, Shari A Wang, Heidi L Kenerson, Mohamed Omer, Kevin D O'Brien, Warren Ladiges, Raymond Yeung, Savitha Subramanian
NEW FINDINGS: What is the central question of this study? Whether chronic oral rapamycin promotes beneficial effects on glucose/lipid metabolism and energy balance when administered to mice with an obesogenic diet rich in saturated fat and sucrose has not been explored. What is the main finding and its importance? Chronic oral rapamycin reduces body weight and fat gain, improves insulin sensitivity, and reduces hepatic steatosis when administered to mice with a high fat high sucrose diet...
August 16, 2018: Experimental Physiology
Shigang Qiao, Guofang Mao, Hua Li, Zhimin Ma, Lei Hong, Huiling Zhang, Chen Wang, Jianzhong An
Background: Chronic overnutrition leads to cardiac dysfunction and insulin (INS) resistance. Dipeptidyl peptidase-4 (DPP-4) improves glucose metabolism and insulin sensitivity in both human and animal models. In this study, we explored whether DPP-4 inhibitor sitagliptin (SIT) is involved in the protection of cardiac function and β -cell function using an obesity female mouse model. Methods: Six-week-old C57BL6/J mice were fed a high fat and fructose Western diet with DPP-4 inhibitor SIT for 12 weeks...
2018: Journal of Diabetes Research
Zhengjie Wang, Xiaolong Xu, Yi Liu, Yongheng Gao, Fei Kang, Baohua Liu, Jing Wang
Brown adipose tissue (BAT) is an important energy metabolic organ that is highly implicated in obesity, type 2 diabetes, and atherosclerosis. Aging is one of the most important determinants of BAT activity. In this study, we used 18 F-FDG PET/CT imaging to assess BAT aging in Lmna-/- mice. The maximum standardized uptake value (SUVMax ) of the BAT was measured, and the target/nontarget (T/NT) values of BAT were calculated. The transcription and the protein expression levels of the uncoupling protein 1 (UCP1), beta3-adrenergic receptor ( β 3-AR), and the PR domain-containing 16 (PRDM16) were measured by quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting or immunohistochemical analysis...
2018: Contrast Media & Molecular Imaging
Sarah Nicolas, Delphine Debayle, Catherine Béchade, Luc Maroteaux, Anne-Sophie Gay, Pascale Bayer, Catherine Heurteaux, Alice Guyon, Joëlle Chabry
Major depression is a psychiatric disorder with complex etiology. About 30% of depressive patients are resistant to antidepressants that are currently available, likely because they only target the monoaminergic systems. Thus, identification of novel antidepressants with a larger action spectrum is urgently required. Epidemiological data indicate high comorbidity between metabolic and psychiatric disorders, particularly obesity and depression. We used a well-characterized anxiety/depressive-like mouse model consisting of continuous input of corticosterone for seven consecutive weeks...
August 16, 2018: Translational Psychiatry
Clara Sanchez-Parra, Cécile Jacovetti, Olivier Dumortier, Kailun Lee, Marie-Line Peyot, Claudiane Guay, Marc Prentki, D Ross Laybutt, Emmanuel Van Obberghen, Romano Regazzi
Pancreatic β-cell expansion throughout the neonatal period is essential to generate the appropriate mass of insulin-secreting cells to maintain blood glucose homeostasis later in life. Hence, defects in this process can predispose to diabetes development at adulthood. Global profiling of the transcripts in pancreatic islets of newborn and adult rats revealed that the expression of the long non-coding RNA H19 is controlled by the transcription factor E2F1 and is profoundly downregulated during the post-natal period...
August 16, 2018: Diabetes
Ling-Fang Wang, Cong-Cong Huang, Yun-Fei Xiao, Xiao-Hui Guan, Xiao-Nv Wang, Qing Cao, Yu Liu, Xuan Huang, Li-Bin Deng, Ke-Yu Deng, Hong-Bo Xin
BACKGROUND/AIMS: Previous studies showed that CD38 deficiency protected heart from ischemia/reperfusion injury and high fat diet (HFD)-induced obesity in mice. However, the role of CD38 in HFD-induced heart injury remains unclear. In the present study, we have investigated the effects and mechanisms of CD38 deficiency on HFD-induced heart injury. METHODS: The metabolites in heart from wild type (WT) and CD38 knockout (CD38-/-) mice were examined using metabolomics analysis...
August 16, 2018: Cellular Physiology and Biochemistry
Cho-Rong Bae, Jun Hino, Hiroshi Hosoda, Mikiya Miyazato, Kenji Kangawa
AIMS: Our previous study revealed that mice transgenic for endothelial-cell-specific overexpression of CNP (E-CNP Tg mice) are protected against the increased fat weight, inflammation, and insulin resistance associated with high-fat diet (HFD)-induced obesity. In addition, E-CNP overexpression prevented abnormal lipid profiles and metabolism and blocked inflammation in the livers of HFD-fed mice. Because obesity, dyslipidemia, and insulin resistance increase the risk of various liver diseases, including non-alcoholic steatohepatitis (NASH), we here studied the role of E-CNP overexpression in the livers of mice in which NASH was induced through feeding of either HFD or a choline-deficient defined l‑amino-acid diet (CDAA)...
August 13, 2018: Life Sciences
Jun Namkung, Ko Eun Shong, Hyeongseok Kim, Chang Myung Oh, Sangkyu Park, Hail Kim
BACKGROUND: Hepatic steatosis is caused by metabolic stress associated with a positive lipid balance, such as insulin resistance and obesity. Previously we have shown the anti-obesity effects of inhibiting serotonin synthesis, which eventually improved insulin sensitivity and hepatic steatosis. However, it is not clear whether serotonin has direct effect on hepatic lipid accumulation. Here, we showed the possibility of direct action of serotonin on hepatic steatosis. METHODS: Mice were treated with para-chlorophenylalanine (PCPA) or LP-533401 to inhibit serotonin synthesis and fed with high fat diet (HFD) or high carbohydrate diet (HCD) to induce hepatic steatosis...
April 25, 2018: Diabetes & Metabolism Journal
Fang Yuan, Jian Ma, Xinxin Xiang, He Lan, Yanhui Xu, Jing Zhao, Yin Li, Weizhen Zhang
Purpose: Adipose tissue inflammation is the key linking obesity to insulin resistance. Over 50% of the interstitial cells in adipose tissue are macrophages, which produce inflammatory cytokines and therefore play an important role in the progression of insulin resistance. Within this classification view, macrophage biology is driven by two polarization phenotypes, M1 (proinflammatory) and M2 (anti-inflammatory). The unique functional receptor of ghrelin, growth hormone secretagogue receptor (GHSR), is a classic seven-transmembrane G protein-coupled receptor that is linked to multiple intracellular signaling pathways...
2018: BioMed Research International
R C Castiglione, C M L Barbosa, L F M Prota, S R Marques-Neto, M Perri-Oliveira, E Helal-Neto, V Morandi, C Barja-Fidalgo, E Bouskela
BACKGROUND AND AIMS: Obesity promotes a persistent inflammatory process in the adipose tissue, activating the endothelium and leading to vascular dysfunction. Preadipocytes can interact with endothelial cells in a paracrine way stimulating angiogenesis. However, the potential of preadipocytes from adipose tissue of high fat diet (HFD) fed animal to stimulate angiogenesis has not been evaluated yet. The aim of this study was to investigate the effects of such diet on the angiogenic potential of preadipocytes in a mice model...
September 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
A V Khamoui, M Desai, M G Ross, H B Rossiter
Exposure to maternal over-nutrition in utero is linked with developmental programming of obesity, metabolic syndrome and cardiovascular disease in offspring, which may be exacerbated by postnatal high-fat (HF) diet. Skeletal muscle mitochondrial function contributes to substrate metabolism and is impaired in metabolic disease. We examined muscle mitochondrial respiration in male and female mice exposed to maternal HF diet in utero, followed by postweaning HF diet until middle age. After in utero exposure to maternal control (Con) or HF diet (45% kcal fat; 39...
August 16, 2018: Journal of Developmental Origins of Health and Disease
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