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mice adipocyte

Carly M Knuth, Willem T Peppler, Logan K Townsend, Paula M Miotto, Anders Gudiksen, David C Wright
KEY POINTS: Mammals defend against cold-induced reductions in body temperature through both shivering and non-shivering thermogenesis. The activation of non-shivering thermogenesis is primarily driven by uncoupling protein-1 in brown adipose tissue and to a lesser degree by the browning of white adipose tissue. Endurance exercise has also been shown to increase markers of white adipose tissue browning. This study aimed to determine whether prior exercise training would alter the response to a cold challenge and if this would be associated with differences in indices of non-shivering thermogenesis...
August 14, 2018: Journal of Physiology
Camille Dumon, Diabe Diabira, Ilona Chudotvorova, Francesca Bader, Semra Sahin, Jinwei Zhang, Christophe Porcher, Gary Wayman, Igor Medina, Jean-Luc Gaiarsa
Brain computations rely on a proper balance between excitation and inhibition which progressively emerges during postnatal development in rodent. g-aminobutyric acid (GABA) neurotransmission supports inhibition in the adult brain but excites immature rodent neurons. Alterations in the timing of the GABA switch contribute to neurological disorders, so unveiling the involved regulators may be a promising strategy for treatment. Here we show that the adipocyte hormone leptin sets the tempo for the emergence of GABAergic inhibition in the newborn rodent hippocampus...
August 14, 2018: ELife
Giorgio Biasiotto, Isabella Zanella, Federica Predolini, Ivonne Archetti, Moris Cadei, Eugenio Monti, Marcello Luzzani, Barbara Pacchetti, Paola Mozzoni, Roberta Andreoli, Giuseppe De Palma, Federico Serana, Annika Smeds, Diego Di Lorenzo
7-Hydroxymatairesinol (7-HMR) is a plant lignan abundant in various concentrations in plant foods. The objective of this study was to test HMRLignan™, a purified form of 7-HMR, and the corresponding Picea abies extract (total extract P. abies; TEP) as dietary supplements on a background of a high-fat diet (HFD)-induced metabolic syndrome in mice and in the 3T3-L1 adipogenesis model. Mice, 3 weeks old, were fed a HFD for 60 d. Subgroups were treated with 3 mg/kg body weight 7-HMR (HMRLignan™) or 10 mg/kg body weight TEP by oral administration...
August 14, 2018: British Journal of Nutrition
Xin Li, Yuhong Cheng, Xiuli Zhong, Bing Zhang, Zhiwei Bao, Yi Zhang, Zhigang Wang
Hyperhomocysteinemia (HHcy) is associated with suppressed lipolytic response in adipocytes/adipose tissue, however, the underlying mechanism remains to be extensively studied. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcriptional factor regulating antioxidant generation, has been recently reported to mediate lipid metabolism. Employing both fully differentiated 3T3-L1 adipocytes and male C57BL/6 mice, in the present study, we investigated the potential involvement of Nrf2 activation in HHcy-mediated lipolytic suppression...
July 2018: Experimental Biology and Medicine
Daorong Feng, Dulguun Amgalan, Rajat Singh, Jianwen Wei, Jennifer Wen, Tszki Peter Wei, Timothy E McGraw, Richard N Kitsis, Jeffrey E Pessin
The t-SNARE protein SNAP23 conventionally functions as a component of the cellular machinery required for intracellular transport vesicle fusion with target membranes and has been implicated in the regulation of fasting glucose levels, BMI, and type 2 diabetes. Surprisingly, we observed that adipocyte-specific KO of SNAP23 in mice resulted in a temporal development of severe generalized lipodystrophy associated with adipose tissue inflammation, insulin resistance, hyperglycemia, liver steatosis, and early death...
August 13, 2018: Journal of Clinical Investigation
Umesh D Wankhade, Ji-Hyeon Lee, Pradeep K Dagur, Hariom Yadav, Michael Shen, Weiping Chen, Ashok B Kulkarni, J Philip McCoy, Toren Finkel, Aaron M Cypess, Sushil G Rane
OBJECTIVE: Beige/brite adipose tissue displays morphological characteristics and beneficial metabolic traits of brown adipose tissue. Previously, we showed that TGF-β signaling regulates the browning of white adipose tissue. Here, we inquired whether TGF-β signals regulated presumptive beige progenitors in white fat and investigated the TGF-β regulated mechanisms involved in beige adipogenesis. METHODS: We deleted TGF-β receptor 1 (TβRI) in adipose tissue (TβRIAdKO mice) and, using flow-cytometry based assays, identified and isolated presumptive beige progenitors located in the stromal vascular cells of white fat...
July 27, 2018: Molecular Metabolism
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
Suzanne A B M Aarts, Myrthe E Reiche, Myrthe den Toom, Linda Beckers, Marion J J Gijbels, Norbert Gerdes, Menno P J de Winther, Esther Lutgens
Obesity is a low-grade inflammatory disease that increases the risk for metabolic disorders. CD40-CD40L signaling plays a central role in obesity-induced inflammation. Genetic deficiency of CD40L in diet-induced obesity (DIO) ameliorates adipose tissue inflammation, hepatic steatosis and increases insulin sensitivity. Unexpectedly, absence of CD40 worsened insulin resistance and caused excessive adipose tissue inflammation and hepatosteatosis. To investigate whether deficiency of macrophage CD40 is responsible for the phenotype observed in the CD40-/- mice, we generated CD40flflLysMcre and fed them a standard (SFD) and 54% high fat obesogenic diet (HFD) for 13 weeks...
2018: PloS One
Hye Eun Lee, Gabsik Yang, Sin-Hee Han, Jeong-Hoon Lee, Tae-Jin An, Jae-Ki Jang, Joo Young Lee
The main function of brown adipose tissue is to dissipate surplus caloric intake into heat energy by thermogenesis, increasing energy expenditure. Inducible brown adipocytes can develop within white adipose tissue (WAT) through a process referred to as browning. Browning of white fat represents a promising strategy for treatment of obesity and the related complications. We investigated whether Glycyrrhiza uralensis and its ingredients modulated adipogenesis through adipocyte browning using 3T3-L1 adipocytes and a high-fat diet (HFD)-induced obesity mice model...
August 7, 2018: Biochemical and Biophysical Research Communications
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
Takashi Yamashita, Katja Lakota, Takashi Taniguchi, Ayumi Yoshizaki, Shinichi Sato, Wen Hong, Xingchun Zhou, Snezn Sodin-Semrl, Feng Fang, Yoshihide Asano, John Varga
The hallmarks of systemic sclerosis (SSc) are autoimmunity, microangiopathy and fibrosis. Skin fibrosis is accompanied by attrition of the dermal white adipose tissue layer, and alterations in the levels and function of adiponectin. Since these findings potentially implicate adiponectin in the pathogenesis of SSc, we employed a novel pharmacological approach to augment adiponectin signaling using AdipoRon, an orally active adiponectin receptor agonist. Chronic treatment with AdipoRon significantly ameliorated bleomycin-induced dermal fibrosis in mice...
August 7, 2018: Scientific Reports
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
Claudia Morganti, Sonia Missiroli, Magdalena Lebiedzinska-Arciszewska, Letizia Ferroni, Lucia Morganti, Mariasole Perrone, Daniela Ramaccini, Savino Occhionorelli, Barbara Zavan, Mariusz R Wieckowski, Carlotta Giorgi
BACKGROUND/OBJECTIVES: Obesity is a complex disease characterized by the accumulation of excess body fat, which is caused by an increase in adipose cell size and number. The major source of adipocytes comes from mesenchymal stem cells (MSCs), although their roles in obesity remain unclear. An understanding of the mechanisms, regulation, and outcomes of adipogenesis is crucial for the development of new treatments for obesity-related diseases. Recently an unexpected role for the tumor suppressor promyelocytic leukemia protein (PML) in hematopoietic stem cell biology and metabolism regulation has come to light, but its role in MSC biology remains unknown...
August 6, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Rui Zhang, Yuan Gao, Xiaotong Zhao, Mei Gao, Yanjun Wu, Yingying Han, Yuemei Qiao, Zheng Luo, Li Yang, Jianfeng Chen, Gaoxiang Ge
Adipocyte progenitors reside in the stromal vascular fraction (SVF) of adipose tissues that are composed of fibroblasts, immune cells, and endothelial cells. It remains to be elucidated how the SVF regulates adipocyte progenitor fate determination and adipose homeostasis. Here, we report that fibroblast-specific protein-1 (FSP1)+ fibroblasts in the SVF are essential to adipose homeostasis. FSP1+ fibroblasts, devoid of adipogenic potential, are adjacent to the preadipocytes in the SVF. Ablation of FSP1+ fibroblasts in mice severely diminishes fat content of adipose depots...
August 2018: PLoS Biology
Xingxing Kong, Ting Yao, Peng Zhou, Lawrence Kazak, Danielle Tenen, Anna Lyubetskaya, Brian A Dawes, Linus Tsai, Barbara B Kahn, Bruce M Spiegelman, Tiemin Liu, Evan D Rosen
Skeletal muscle and brown adipose tissue (BAT) are functionally linked, as exercise increases browning via secretion of myokines. It is unknown whether BAT affects muscle function. Here, we find that loss of the transcription factor IRF4 in BAT (BATI4KO) reduces exercise capacity, mitochondrial function, ribosomal protein synthesis, and mTOR signaling in muscle and causes tubular aggregate formation. Loss of IRF4 induces myogenic gene expression in BAT, including the secreted factor myostatin, a known inhibitor of muscle function...
July 25, 2018: Cell Metabolism
Changkeun Kang, Kayoko Saso, Kazushige Ota, Masahito Kawazu, Takeshi Ueda, Hitoshi Okada
Obesity is a serious global health issue; however, the roles of genetics and epigenetics in the onset and progression of obesity are still not completely understood. The aim of this study was to determine the role of Kdm4b, which belongs to a subfamily of histone demethylases, in adipogenesis and fat metabolism in vivo. We established conditional Kdm4b knockout mice. Inactivation of Kdm4b in adipocytes (K4bKO) induced profound obesity in mice on a high fat diet (HFD). The HFD-fed K4bKO mice exhibited an increased volume of fat mass and higher expression levels of adipogenesis-related genes...
August 2, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Xiao-Xi Pan, Jiu-Mei Cao, Fan Cai, Cheng-Chao Ruan, Fang Wu, Ping-Jin Gao
PURPOSE: Pathological changes of the perivascular adipose tissue (PVAT) are directly associated with increased risk of age-related vascular diseases. MicroRNAs regulate adipocyte biological functions including adipogenic differentiation and white adipocyte browning. The present study aims to determine whether miR-146b-3p is involved in the regulation of perivascular adipocyte browning during aging. METHODS: We utilized a cold-induced animal model to investigate the effect of aging on perivascular adipocyte browning...
August 2, 2018: Cardiovascular Drugs and Therapy
Anthony Ravussin, Yun-Hee Youm, Jil Sander, Seungjin Ryu, Kim Nguyen, Luis Varela, Gerald I Shulman, Sviatoslav Sidorov, Tamas L Horvath, Joachim L Schultze, Vishwa Deep Dixit
Inducers of satiety are drug targets for weight loss to mitigate obesity-associated diseases. Nucleobindin-2 (Nucb2) is thought to be post-translationally processed into bioactive nesfatin-1 peptide, which reportedly induces satiety, causes weight loss, and thus improves insulin sensitivity. Here, we show that deletion of Nucb2 did not affect food intake or adiposity and, instead, caused insulin resistance in mice fed a high-fat diet. In addition, ablation of Nucb2 in orexigenic hypothalamic Agrp neurons did not affect food intake, and nesfatin-1 was detectable in serum, despite global deletion of Nucb2 protein...
July 31, 2018: Cell Reports
Ellen Vercalsteren, Christine Vranckx, H Roger Lijnen, Bianca Hemmeryckx, Ilse Scroyen
Intestinal alkaline phosphatase 3 (AKP3) is an enzyme that was reported to play a role in lipid metabolism and to prevent high fat diet-induced metabolic syndrome in mice. To investigate a potential functional role of AKP3 in diet-induced adiposity and metabolic health, we have kept male and female wild-type or AKP3 deficient mice on a high fat diet for 15 weeks to induce obesity and compared those with mice kept on standard fat diet. Body weight as well as adipose tissue mass were statistically significantly higher upon high fat diet feeding for mice of both genders and genotypes...
July 31, 2018: Adipocyte
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