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Brown adipose glucose tolerance

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https://www.readbyqxmd.com/read/28611668/selective-tissue-distribution-mediates-tissue-dependent-ppar%C3%AE-activation-and-insulin-sensitization-by-int131-a-selective-ppar%C3%AE-modulator
#1
Xinni Xie, Wei Chen, Ning Zhang, Mei Yuan, Cheng Xu, Zhibing Zheng, Hua Li, Lili Wang
The mechanisms underlying the enhancement of insulin sensitivity by selective peroxisome proliferator-activated receptor γ modulators (sPPARγMs) are still not completely known. Here, the representative sPPARγM, INT131, was used as a probe to investigate the insulin-sensitizing mechanisms of sPPARγM in the context of tissue selective compound distribution and PPARγ regulation. First, 30 mg kg(-1) INT131 was observed to produce an insulin-sensitizing effect comparable to that of 10 mg kg(-1) rosiglitazone (RSG) in both db/db and DIO mice using the oral glucose and insulin tolerance tests...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28597936/the-beneficial-metabolic-effects-of-insulin-sensitizers-are-not-attenuated-by-mitochondrial-pyruvate-carrier-2-hypomorphism
#2
Patrick A Vigueira, Kyle S McCommis, Wesley T Hodges, George G Schweitzer, Serena L Cole, Lalita Oonthonpan, Eric B Taylor, William G McDonald, Rolf F Kletzien, Jerry R Colca, Brian N Finck
Rosiglitazone and pioglitazone are thiazolidinedione (TZD) compounds that have been used clinically as insulin-sensitizing drugs and are generally believed to mediate their effects via activation of the peroxisome proliferator-activated receptor γ (PPARγ). Recent work has shown that it is possible to synthesize TZD compounds with potent insulin-sensitizing effects and markedly-diminished affinity for PPARγ. Both clinically-used TZDs and investigational PPARγ-sparing TZDs, such as MSDC-0602, interact with the mitochondrial pyruvate carrier (MPC) and inhibit its activity...
June 9, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28588097/high-intensity-interval-training-and-calorie-restriction-promote-remodeling-of-glucose-and-lipid-metabolism-in-diet-induced-obesity
#3
Rachel A H Davis, Jacob E Halbrooks, Emily Watkins, Gordon Fisher, Gary R Hunter, Tim R Nagy, Eric P Plaisance
Calorie restriction (CR) decreases adiposity, but the magnitude and defense of weight loss is less than predicted due to reductions in total daily energy expenditure (TEE). The purpose of the current investigation was to determine if high-intensity interval training (HIIT) would increase markers of sympathetic activation in white adipose tissue (WAT) and rescue CR-mediated reductions in EE to a greater extent than moderate-intensity aerobic exercise training (MIT). Thirty-two 5-wk old male C57BL/6J mice were placed on ad libitum HFD for 11 weeks followed by randomization to one of four groups (n = 8 per group) for an additional 15 weeks: 1) CON (remain on HFD); 2) CR (25% lower energy intake); 3) CR+HIIT (25% energy deficit created by 12...
June 6, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28586387/salsalate-ameliorates-metabolic-disturbances-by-reducing-inflammation-in-spontaneously-hypertensive-rats-expressing-human-c-reactive-protein-and-by-activating-brown-adipose-tissue-in-nontransgenic-controls
#4
Jaroslava Trnovská, Jan Šilhavý, Ondřej Kuda, Vladimír Landa, Václav Zídek, Petr Mlejnek, Miroslava Šimáková, Hynek Strnad, Vojtěch Škop, Olena Oliyarnyk, Ludmila Kazdová, Martin Haluzík, Michal Pravenec
Chronic low-grade inflammation plays an important role in the pathogenesis of insulin resistance. In the current study, we tested the effects of salsalate, a non-steroidal anti-inflammatory drug, in an animal model of inflammation and metabolic syndrome using spontaneously hypertensive rats (SHR) that transgenically express human C-reactive protein (SHR-CRP rats). We treated 15-month-old male transgenic SHR-CRP rats and nontransgenic SHR with salsalate (200 mg/kg/day) mixed as part of a standard diet for 4 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28580278/fgf21-does-not-require-adipocyte-amp-activated-protein-kinase-ampk-or-the-phosphorylation-of-acetyl-coa-carboxylase-acc-to-mediate-improvements-in-whole-body-glucose-homeostasis
#5
Emilio P Mottillo, Eric M Desjardins, Andreas M Fritzen, Vito Z Zou, Justin D Crane, Julian M Yabut, Bente Kiens, Derek M Erion, Adhiraj Lanba, James G Granneman, Saswata Talukdar, Gregory R Steinberg
OBJECTIVE: Fibroblast growth factor 21 (FGF21) shows great potential for the treatment of obesity and type 2 diabetes, as its long-acting analogue reduces body weight and improves lipid profiles of participants in clinical studies; however, the intracellular mechanisms mediating these effects are poorly understood. AMP-activated protein kinase (AMPK) is an important energy sensor of the cell and a molecular target for anti-diabetic medications. This work examined the role of AMPK in mediating the glucose and lipid-lowering effects of FGF21...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28555111/novel-glp-1-analog-supaglutide-reduces-hfd-induced-obesity-associated-with-increased-ucp-1-in-white-adipose-tissue-in-mice
#6
Yun Wan, Xi Bao, Jiabao Huang, Xiangyu Zhang, Wenjuan Liu, Qiaoli Cui, Dongdong Jiang, Zhihong Wang, Rui Liu, Qinghua Wang
GLP-1, an important incretin hormone plays an important role in the regulation of glucose homeostasis. However, the therapeutic use of native GLP-1 is limited due to its short half-life. We recently developed a novel GLP-1 mimetics (supaglutide) by genetically engineering recombinant fusion protein production techniques. We demonstrated that this formulation possessed long-lasting GLP-1 actions and was effective in glycemic control in both type 1 and type 2 diabetes rodent models. Here, we investigated the effects of supaglutide in regulating energy homeostasis in obese mice...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28549558/the-kv1-3-channel-blocker-vm24-enhances-muscle-glucose-transporter-4-mobilization-but-does-not-reduce-body-weight-gain-in-diet-induced-obese-male-rats
#7
Lorraine Jaimes-Hoy, Georgina B Gurrola, Miguel Cisneros, Patricia Joseph-Bravo, Lourival D Possani, Jean-Louis Charli
AIMS: Voltage-gated potassium channels 1.3 (Kv1.3) can be targeted to reduce diet-induced obesity and insulin resistance in mice. Since species-specific differences in Kv1.3 expression and pharmacology have been observed, we tested the effect of Vm24, a high-affinity specific blocker of Kv1.3 channels from Vaejovis mexicanus smithi, on body weight (BW), glucose tolerance and insulin resistance in diet-induced obese rats. MATERIALS AND METHODS: Young adult male Wistar rats were switched to a high-fat/high-fructose (HFF) diet...
May 23, 2017: Life Sciences
https://www.readbyqxmd.com/read/28543963/ageing-is-associated-with-brown-adipose-tissue-remodelling-and-loss-of-white-fat-browning-in-female-c57bl-6-mice
#8
Leidyanne Ferreira Gonçalves, Thaissa Queiroz Machado, Camila Castro-Pinheiro, Nathalia Guimaraes de Souza, Karen Jesus Oliveira, Caroline Fernandes-Santos
Fat storage changes throughout life and affects body metabolism. Ageing impact on brown (BAT) and white adipose tissue (WAT) deserves attention, especially in females, because they are less prone to age-induced weight gain. While in male mice the impact of ageing on adipose tissue remodelling is well characterized, the effects in female mice remain largely unclear. Thus, we investigated BAT and WAT remodelling during ageing in female C57BL/6 mice. At 3 months, body weight was 24 ± 0.3 g (mean±SD), and it increased from 6 to 9 months of age (+20%, P < 0...
May 24, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28533422/paternal-hyperglycemia-in-rats-exacerbates-the-development-of-obesity-in-offspring
#9
Xiaoqin Shi, Xinyu Li, Yi Hou, Xuemei Cao, Yuyao Zhang, Heng Wang, Hongying Wang, Chuan Peng, Jibin Li, Qifu Li, Chaodong Wu, Xiaoqiu Xiao
Parental history with obesity or diabetes will increase the risk for developing metabolic diseases in offspring. However, literatures as to transgenerational inheritance of metabolic dysfunctions through male lineage are relatively scarce. In current study, we aimed to evaluate influences of paternal hyperglycemia on metabolic phenotypes in offspring. Male SD rats were ip injected with streptozotocin (STZ) or citrate buffer (CB, as control). STZ-injected rats with glucose levels higher than 16 mM were selected to breed with normal female rats...
May 22, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28533304/modulation-of-the-gut-microbiota-impacts-non-alcoholic-fatty-liver-disease-a-potential-role-for-bile-acids
#10
Aafke Wf Janssen, Tom Houben, Saeed Katiraei, Wieneke Dijk, Lily Boutens, Nieke van der Bolt, Zeneng Wang, J Mark Brown, Stanley L Hazen, Stéphane Mandard, Ronit Shiri-Sverdlov, Folkert Kuipers, Ko Willems van Dijk, Jacques Vervoort, Rinke Stienstra, Guido Jej Hooiveld, Sander Kersten
Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber guar gum and suppressing the gut bacteria via chronic oral administration of antibiotics. Guar gum feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance...
May 22, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28442777/serotonin-transporter-deficiency-drives-estrogen-dependent-obesity-and-glucose-intolerance
#11
Weibin Zha, Horace T B Ho, Tao Hu, Mary F Hebert, Joanne Wang
Depression and use of antidepressant medications are both associated with increased risk of obesity, potentially attributed to a reduced serotonin transporter (SERT) function. However, how SERT deficiency promotes obesity is unknown. Here, we demonstrated that SERT (-/-) mice display abnormal fat accumulation in both white and brown adipose tissues, glucose intolerance and insulin resistance while exhibiting suppressed aromatase (Cyp19a1) expression and reduced circulating 17β-estradiol levels. 17β-estradiol replacement in SERT (-/-) mice reversed the obesity and glucose intolerance, supporting a role for estrogen in SERT deficiency-associated obesity and glucose intolerance...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28437200/effects-of-dietary-macronutrient-composition-on-fndc5-and-irisin-in-mice-skeletal-muscle
#12
Simone Moreira de Macêdo, Deborah de Farias Lelis, Keila Lopes Mendes, Carlos Alberto de Carvalho Fraga, Igor V Brandi, Jonh David Feltenberger, Lucyana Conceição Farias, André Luiz Sena Guimarães, Alfredo Maurício Batista de Paula, Sérgio Henrique de Sousa Santos
BACKGROUND: Fibronectin type III domain containing 5 (FNDC5) and its protein product Irisin are therapeutic targets for obesity-associated disorders. Irisin plays an important role in energy regulation, inducing browning of white adipocytes, and improving obesity. We aimed to investigate the association between muscle Irisin expression and dietary quality. METHODS: Twenty-eight female mice were divided into four groups and fed the following experimental diets for 60 days: standard diet (SD), high-carbohydrate diet (HCD), high-fat diet (HFD), and high-protein diet (HPD)...
May 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28414465/topical-intestinal-aminoimidazole-agonists-of-g-protein-coupled-bile-acid-receptor-1-promote-glucagon-like-peptide-1-secretion-and-improve-glucose-tolerance
#13
Manuel Lasalle, Vanessa Hoguet, Nathalie Hennuyer, Florence Leroux, Catherine Piveteau, Loïc Belloy, Sophie Lestavel, Emmanuelle Vallez, Emilie Dorchies, Isabelle Duplan, Emmanuel Sevin, Maxime Culot, Fabien Gosselet, Rajaa Boulahjar, Adrien Herledan, Bart Staels, Benoit Deprez, Anne Tailleux, Julie Charton
The role of the G-protein-coupled bile acid receptor TGR5 in various organs, tissues, and cell types, specifically in intestinal endocrine L-cells and brown adipose tissue, has made it a promising therapeutical target in several diseases, especially type-2 diabetes and metabolic syndrome. However, recent studies have shown deleterious on-target effects of systemic TGR5 agonists. To avoid these systemic effects while stimulating glucagon-like peptide-1 (GLP-1) secreting enteroendocrine L-cells, we have designed TGR5 agonists with low intestinal permeability...
May 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28404627/multiphasic-regulation-of-systemic-and-peripheral-organ-metabolic-responses-to-cardiac-hypertrophy
#14
Chong Wee Liew, Shanshan Xu, Xuerong Wang, Maximilian McCann, Hyerim Whang Kong, Andrew C Carley, Jingbo Pang, Giamila Fantuzzi, J Michael O'Donnell, E Douglas Lewandowski
BACKGROUND: Reduced fat oxidation in hypertrophied hearts coincides with a shift of carnitine palmitoyl transferase I from muscle to increased liver isoforms. Acutely increased carnitine palmitoyl transferase I in normal rodent hearts has been shown to recapitulate the reduced fat oxidation and elevated atrial natriuretic peptide message of cardiac hypertrophy. METHODS AND RESULTS: Because of the potential for reduced fat oxidation to affect cardiac atrial natriuretic peptide, and thus, induce adipose lipolysis, we studied peripheral and systemic metabolism in male C57BL/6 mice model of transverse aortic constriction in which left ventricular hypertrophy occurred by 2 weeks without functional decline until 16 weeks (ejection fraction, -45...
April 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28394923/effects-and-underlying-mechanisms-of-irisin-on-the-proliferation-and-apoptosis-of-pancreatic-%C3%AE-cells
#15
Shiwei Liu, Fang Du, Xin Li, Mingming Wang, Ruixue Duan, Jiaxin Zhang, Yaru Wu, Qi Zhang
Pancreatic β cell dysfunction and reduction due to glucose toxicity play a crucial role in the development of type 2 diabetes mellitus (T2DM). Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promotes cell proliferation and protects cells from apoptosis. However, the effects of irisin on pancreatic β cells are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28378930/hepatic-fxr-shp-axis-modulates-systemic-glucose-and-fatty-acid-homeostasis-in-aged-mice
#16
Kang Ho Kim, Sungwoo Choi, Ying Zhou, Eun Young Kim, Jae Man Lee, Pradip K Saha, Sayeepriyadarshini Anakk, David D Moore
The nuclear receptors farnesoid X receptor (FXR; NR1H4) and small heterodimer partner (SHP; NR0B2) play crucial roles in bile acid homeostasis. Global disruption of both FXR and SHP signaling (DKO) causes severe cholestasis and liver injury at early ages. Here, we report an unexpected beneficial impact on glucose and fatty acid metabolism in aged DKO mice, which show suppressed body weight gain and adiposity when maintained on normal chow. This phenotype was not observed in single Fxr or Shp knockouts. Liver-specific Fxr/Shp double knockout (FS(LK) °) mice fully phenocopied the DKO mice, with lower hepatic triglyceride accumulation, improved glucose/insulin tolerance and accelerated fatty acid utilization...
April 5, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28346411/the-cold-induced-lipokine-12-13-dihome-promotes-fatty-acid-transport-into-brown-adipose-tissue
#17
Matthew D Lynes, Luiz O Leiria, Morten Lundh, Alexander Bartelt, Farnaz Shamsi, Tian Lian Huang, Hirokazu Takahashi, Michael F Hirshman, Christian Schlein, Alexandra Lee, Lisa A Baer, Francis J May, Fei Gao, Niven R Narain, Emily Y Chen, Michael A Kiebish, Aaron M Cypess, Matthias Blüher, Laurie J Goodyear, Gökhan S Hotamisligil, Kristin I Stanford, Yu-Hua Tseng
Brown adipose tissue (BAT) and beige adipose tissue combust fuels for heat production in adult humans, and so constitute an appealing target for the treatment of metabolic disorders such as obesity, diabetes and hyperlipidemia. Cold exposure can enhance energy expenditure by activating BAT, and it has been shown to improve nutrient metabolism. These therapies, however, are time consuming and uncomfortable, demonstrating the need for pharmacological interventions. Recently, lipids have been identified that are released from tissues and act locally or systemically to promote insulin sensitivity and glucose tolerance; as a class, these lipids are referred to as 'lipokines'...
May 2017: Nature Medicine
https://www.readbyqxmd.com/read/28323915/insulin-igf-1-and-gh-receptors-are-altered-in-an-adipose-tissue-depot-specific-manner-in-male-mice-with-modified-gh-action
#18
Rikke Hjortebjerg, Darlene E Berryman, Ross Comisford, Stuart J Frank, Edward O List, Mette Bjerre, Jan Frystyk, John J Kopchick
Growth hormone (GH) is an important determinant of glucose homeostasis and adipose tissue (AT) function. Using seven-month-old bovine GH transgenic (bGH) mice and GH receptor knockout (GHR-/-) mice, we examined whether changes in GH action affect glucose, insulin, and pyruvate tolerance and AT expression patterns of proteins involved in the interrelated signaling pathways of GH, insulin-like growth factor-1 (IGF-1), and insulin. Furthermore, we searched for AT depot-specific differences in control mice that may explain why GH effects depend on AT location...
February 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28291835/adipocyte-arrestin-domain-containing-3-protein-arrdc3-regulates-uncoupling-protein-1-ucp1-expression-in-white-adipose-independently-of-canonical-changes-in-%C3%AE-adrenergic-receptor-signaling
#19
Shannon H Carroll, Ellen Zhang, Bing F Wang, Katherine B LeClair, Arifeen Rahman, David E Cohen, Jorge Plutzky, Parth Patwari, Richard T Lee
Adaptive thermogenesis and cold-induced activation of uncoupling protein 1 (Ucp1) in brown adipose tissue in rodents is well-described and attributed to sympathetic activation of β-adrenergic signaling. The arrestin domain containing protein Arrdc3 is a regulator of obesity in mice and also appears linked to obesity in humans. We generated a mouse with conditional deletion of Arrdc3, and here we present evidence that genetic ablation of Arrdc3 specifically in adipocytes results in increased Ucp1 expression in subcutaneous and parametrial adipose tissue...
2017: PloS One
https://www.readbyqxmd.com/read/28288167/erythropoietin-epo-ameliorates-obesity-and-glucose-homeostasis-by-promoting-thermogenesis-and-endocrine-function-of-classical-brown-adipose-tissue-bat-in-diet-induced-obese-mice
#20
Kazuki Kodo, Satoru Sugimoto, Hisakazu Nakajima, Jun Mori, Ikuyo Itoh, Shota Fukuhara, Keiichi Shigehara, Taichiro Nishikawa, Kitaro Kosaka, Hajime Hosoi
Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly has beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play a role in EPO's anti-obesity and anti-diabetic effects in diet-induced obese mice. Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD-Con), and half were additionally given an intraperitoneal injection of recombinant human EPO (200 IU/kg) (HFD-EPO) thrice a week for four weeks...
2017: PloS One
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