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Brown adipose glucose tolerance

Antonia Sassmann-Schweda, Pratibha Singh, Cong Tang, Astrid Wietelmann, Nina Wettschureck, Stefan Offermanns
Obesity is an increasing health problem worldwide, and nonsurgical strategies to treat obesity have remained rather inefficient. We here show that acute loss of TGF-β-activated kinase 1 (TAK1) in adipocytes results in an increased rate of apoptotic adipocyte death and increased numbers of M2 macrophages in white adipose tissue. Mice with adipocyte-specific TAK1 deficiency have reduced adipocyte numbers and are resistant to obesity induced by a high-fat diet or leptin deficiency. In addition, adipocyte-specific TAK1-deficient mice under a high-fat diet showed increased energy expenditure, which was accompanied by enhanced expression of the uncoupling protein UCP1...
May 19, 2016: JCI Insight
J Brenmoehl, D Ohde, E Albrecht, C Walz, A Tuchscherer, A Hoeflich
For the assessment of genetic or conditional factors of fat cell browning, novel and polygenic animal models are required. Therefore, the long-term selected polygenic mouse line DUhTP originally established in Dummerstorf for high treadmill performance is used. DUhTP mice are characterized by increased fat accumulation in the sedentary condition and elevated fat mobilization during mild voluntary physical activity. In the present study, the phenotype of fat cell browning of subcutaneous fat and a potential effect on oral glucose tolerance, an indicator of metabolic health, were addressed in DUhTP mice...
September 30, 2016: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
Brennan K Smith, Rebecca J Ford, Eric M Desjardins, Alex E Green, Meghan C Hughes, Vanessa P Houde, Emily A Day, Katarina Marcinko, Justin D Crane, Emilio P Mottillo, Christopher G R Perry, Bruce E Kemp, Mark A Tarnopolsky, Gregory R Steinberg
Salsalate is a prodrug of salicylate that lowers blood glucose in patients with type 2 diabetes (T2D) and reduces non-alcoholic fatty liver disease (NAFLD) in animal models; however, the mechanism mediating these effects is unclear. Salicylate directly activates AMP-activated protein kinase (AMPK) via the β1 subunit but whether salsalate requires AMPK β1 to improve T2D and NAFLD has not been examined. Therefore, wild-type (WT) and AMPK β1 knockout mice (AMPK β1KO) were treated with a salsalate dose resulting in clinically relevant serum salicylate concentrations (∼1 mM)...
August 23, 2016: Diabetes
Rosario Pardo, Natividad Blasco, Maria Vilà, Daniel Beiroa, Rubén Nogueiras, Xavier Cañas, Rafael Simó, Daniel Sanchis, Josep A Villena
Brown adipose tissue (BAT) plays a central role in the regulation of whole-body energy and glucose homeostasis owing to its elevated capacity for lipid and glucose oxidation. The BAT thermogenic function, which is essential for the defense of body temperature against exposure to low environmental temperatures, relies on the expression in the inner membrane of brown adipocyte's mitochondria of uncoupling protein-1, a protein that uncouples substrate oxidation from oxidative phosphorylation and leads to the production of heat instead of ATP...
October 2016: Endocrinology
Tizhong Shan, Yan Xiong, Pengpeng Zhang, Zhiguo Li, Qingyang Jiang, Pengpeng Bi, Feng Yue, Gongshe Yang, Yizhen Wang, Xiaoqi Liu, Shihuan Kuang
Brown adipose tissue (BAT) dissipates energy through Ucp1-mediated uncoupled respiration and its activation may represent a therapeutic strategy to combat obesity. Here we show that Lkb1 controls BAT expansion and UCP1 expression in mice. We generate adipocyte-specific Lkb1 knockout mice and show that, compared with wild-type littermates, these mice exhibit elevated UCP1 expression in BAT and subcutaneous white adipose tissue, have increased BAT mass and higher energy expenditure. Consequently, KO mice have improved glucose tolerance and insulin sensitivity, and are more resistant to high-fat diet (HFD)-induced obesity...
2016: Nature Communications
Lance A Stechschulte, Bin Qiu, Manya Warrier, Terry D Hinds, Man Zhang, Hao Gu, Yuxue Xu, Saja S Khuder, Lucia Russo, Sonia M Najjar, Beata Lecka-Czernik, Weidong Yong, Edwin R Sanchez
FK506-binding protein-51 (FKBP51) is a molecular cochaperone recently shown to be a positive regulator of peroxisome proliferator-activated receptor (PPAR)γ, the master regulator of adipocyte differentiation and function. In cellular models of adipogenesis, loss of FKBP51 not only reduced PPARγ activity but also reduced lipid accumulation, suggesting that FKBP51 knock-out (KO) mice might have insufficient development of adipose tissue and lipid storage ability. This model was tested by examining wild-type (WT) and FKBP51-KO mice under regular and high-fat diet conditions...
October 2016: Endocrinology
Xiaoshuang Zhou, Rongshan Li, Xinyan Liu, Lihua Wang, Peng Hui, Lawrence Chan, Pradip K Saha, Zhaoyong Hu
Irisin reportedly promotes the conversion of preadipocytes into "brown-like" adipocytes within subcutaneous white adipose tissue (WAT) via a mechanism that stimulates UCP-1 expression. An increase in plasma irisin has been associated with improved obesity and insulin resistance in mice with type 2 diabetes. But whether a low level of irisin stimulates the development of obesity has not been determined. In studying mice with muscle-specific constitutive ROCK1 activation (mCaROCK1), we found that irisin production was down-regulated and the mice developed obesity and insulin resistance...
2016: Scientific Reports
James W Larrick, Jasmine W Larrick, Andrew R Mendelsohn
Until recently, the mechanism of adaptive thermogenesis was ascribed to the expression of uncoupling protein 1 (UCP1) in brown and beige adipocytes. UCP1 is known to catalyze a proton leak of the inner mitochondrial membrane, resulting in uncoupled oxidative metabolism with no production of adenosine triphosphate and increased energy expenditure. Thus increasing brown and beige adipose tissue with augmented UCP1 expression is a viable target for obesity-related disorders. Recent work demonstrates an UCP1-independent pathway to uncouple mitochondrial respiration...
August 2016: Rejuvenation Research
Sandra Côté, Valérie Gagné-Ouellet, Simon-Pierre Guay, Catherine Allard, Andrée-Anne Houde, Patrice Perron, Jean-Patrice Baillargeon, Daniel Gaudet, Renée Guérin, Diane Brisson, Marie-France Hivert, Luigi Bouchard
BACKGROUND: Children exposed to gestational diabetes mellitus (GDM) are at a higher risk of developing obesity and type 2 diabetes. This susceptibility might involve brown adipose tissue (BAT), which is suspected to protect against obesity. The objective of this study is to assess whether fetal exposure to maternal hyperglycemia is associated with DNA methylation variations in genes involved in BAT genesis and activation. METHODS: DNA methylation levels at the PRDM16, BMP7, CTBP2, and PPARGC1α gene loci were measured in placenta samples using bisulfite pyrosequencing in E-21 (n = 133; 33 cases of GDM) and the HumanMethylation450 array in Gen3G (n = 172, all from non-diabetic women) birth cohorts...
2016: Clinical Epigenetics
Joseph F Pierre, Kristina B Martinez, Honggang Ye, Anuradha Nadimpalli, Timothy C Morton, Jinghui Yang, Qiang Wang, Noelle Patno, Eugene B Chang, Deng Ping Yin
The metabolic benefits induced by gastric bypass, currently the most effective treatment for morbid obesity, are associated with bile acid (BA) delivery to the distal intestine. However, mechanistic insights into BA signaling in the mediation of metabolic benefits remain an area of study. The bile diversion () mouse model, in which the gallbladder is anastomosed to the distal jejunum, was used to test the specific role of BA in the regulation of glucose and lipid homeostasis. Metabolic phenotype, including body weight and composition, glucose tolerance, energy expenditure, thermogenesis genes, total BA and BA composition in the circulation and portal vein, and gut microbiota were examined...
August 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Tizhong Shan, Pengpeng Zhang, Qinyang Jiang, Yan Xiong, Yizhen Wang, Shihuan Kuang
AIMS/HYPOTHESIS: The in vivo role of mechanistic target of rapamycin (mTOR) in the development and function of adipose tissue, especially brown adipose tissue (BAT), is not well understood. Here, we aimed to assess the effect of mTOR (also known as Mtor) knockout on adipose tissues and systemic energy metabolism. METHODS: We generated adipocyte-specific mTOR-knockout mice (Adipoq-mTOR) by crossing adiponectin-Cre (Adipoq-Cre) mice with mTOR (flox/flox) mice. The mice were then subjected to morphological, physiological (indirect calorimetry, glucose and insulin tolerance tests) and gene expression analyses to determine the role of mTOR in adipose tissues...
September 2016: Diabetologia
Sirazul A Sahariah, Ramesh D Potdar, Meera Gandhi, Sarah H Kehoe, Nick Brown, Harshad Sane, Patsy J Coakley, Ella Marley-Zagar, Harsha Chopra, Devi Shivshankaran, Vanessa A Cox, Alan A Jackson, Barrie M Margetts, Caroline Hd Fall
BACKGROUND: Prospective observational studies suggest that maternal diets rich in leafy green vegetables and fruit may help prevent gestational diabetes mellitus (GDM). OBJECTIVE: Our objective was to test whether increasing women's dietary intake of leafy green vegetables, fruit, and milk before conception and throughout pregnancy reduced their risk of GDM. METHODS: Project SARAS ("excellent") (2006-2012) was a nonblinded, individually randomized, controlled trial in women living in slums in the city of Mumbai, India...
July 2016: Journal of Nutrition
Huijuan Zhu, Xiangqing Wang, Hui Pan, Yufei Dai, Naishi Li, Linjie Wang, Hongbo Yang, Fengying Gong
OBJECTIVES: Safflower yellow (SY) is the main effective ingredient of Carthamus tinctorius L. It has been reported that SY plays an important role in anti-inflammation, anti-platelet aggregation, and inhibiting thrombus formation. In present study, we try to investigate the effects of SY on body weight, body fat mass, insulin sensitivity in high fat diet (HFD)-induced obese mice. METHODS: HFD-induced obese male ICR mice were intraperitoneally injected with SY (120 mg kg(-1)) daily...
2016: Frontiers in Pharmacology
Tim J Schulz, Antonia Graja, Tian Lian Huang, Ruidan Xue, Ding An, Sophie Poehle-Kronawitter, Matthew D Lynes, Alexander Tolkachov, Lindsay E O'Sullivan, Michael F Hirshman, Michael Schupp, Laurie J Goodyear, Yuji Mishina, Yu-Hua Tseng
AIMS/HYPOTHESIS: Adipose tissue dysfunction is a prime risk factor for the development of metabolic disease. Bone morphogenetic proteins (BMPs) have previously been implicated in adipocyte formation. Here, we investigate the role of BMP signalling in adipose tissue health and systemic glucose homeostasis. METHODS: We employed the Cre/loxP system to generate mouse models with conditional ablation of BMP receptor 1A in differentiating and mature adipocytes, as well as tissue-resident myeloid cells...
August 2016: Diabetologia
Sara L Svahn, Leif Väremo, Britt G Gabrielsson, Eduard Peris, Intawat Nookaew, Louise Grahnemo, Ann-Sofie Sandberg, Ingrid Wernstedt Asterholm, John-Olov Jansson, Jens Nielsen, Maria E Johansson
Dietary polyunsaturated fatty acids (PUFA) are suggested to modulate immune function, but the effects of dietary fatty acids composition on gene expression patterns in immune organs have not been fully characterized. In the current study we investigated how dietary fatty acids composition affects the total transcriptome profile, and especially, immune related genes in two immune organs, spleen (SPL) and bone marrow cells (BMC). Four tissues with metabolic function, skeletal muscle (SKM), white adipose tissue (WAT), brown adipose tissue (BAT), and liver (LIV), were investigated as a comparison...
2016: PloS One
Bruno Araújo Serra Pinto, Thamys Marinho Melo, Karla Frida Torres Flister, Lucas Martins França, Daniela Kajihara, Leonardo Yuji Tanaka, Francisco Rafael Martins Laurindo, Antonio Marcus de Andrade Paes
Early-life environmental insults have been shown to promote long-term development of chronic non-communicable diseases, including metabolic disturbances and mental illnesses. As such, premature consumption of high-sugar foods has been associated to early onset of detrimental outcomes, whereas underlying mechanisms are still poorly understood. In the present study, we sought to investigate whether early and sustained exposure to high-sucrose diet promotes metabolic disturbances that ultimately might anticipate neurological injuries...
August 2016: Metabolic Brain Disease
Derek A Dionne, Søs Skovsø, Nicole M Templeman, Susanne M Clee, James D Johnson
Antiadiposity effects of caloric restriction (CR) are associated with reduced insulin/IGF-1 signaling, but it is unclear whether the effects of CR would be additive to genetically reducing circulating insulin. To address this question, we examined female Ins1(+/-):Ins2(-/-) mice and Ins1(+/+):Ins2(-/-) littermate controls on either an ad libitum or 60% CR diet. Although Igf1 levels declined as expected, CR was unable to reduce plasma insulin levels in either genotype below their ad libitum-fed littermate controls...
July 2016: Endocrinology
Laelie A Snook, Rebecca E K MacPherson, Cynthia M F Monaco, Scott Frendo-Cumbo, Laura Castellani, Willem T Peppler, Zachary G Anderson, Samyra L Buzelle, Paul J LeBlanc, Graham P Holloway, David C Wright
High-fat diets rapidly cause weight gain and glucose intolerance. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice were exercise-trained by treadmill running (1 h/day, 5 days/wk) for 4 wk. Twenty-four hours after the final bout of exercise, mice were provided with a high-fat diet (HFD; 60% kcal from lard) for 4 days, with no further exercise. In mice fed the HFD prior to exercise training, the results were blunted weight gain, reduced fat mass, and a slight attenuation in glucose intolerance that was mirrored by greater insulin-induced Akt phosphorylation in skeletal muscle compared with sedentary mice fed the HFD...
August 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Lorna M Dickson, Shriya Gandhi, Brian T Layden, Ronald N Cohen, Barton Wicksteed
Adipose tissue PKA has roles in adipogenesis, lipolysis, and mitochondrial function. PKA transduces the cAMP signal downstream of G protein-coupled receptors, which are being explored for therapeutic manipulation to reduce obesity and improve metabolic health. This study aimed to determine the overall physiological consequences of PKA activation in adipose tissue. Mice expressing an activated PKA catalytic subunit in adipose tissue (Adipoq-caPKA mice) showed increased PKA activity in subcutaneous, epididymal, and mesenteric white adipose tissue (WAT) depots and brown adipose tissue (BAT) compared with controls...
July 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Shangang Zhao, Yves Mugabo, Gwynne Ballentine, Camille Attane, Jose Iglesias, Pegah Poursharifi, Dongwei Zhang, Thuy Anne Nguyen, Heidi Erb, Raphael Prentki, Marie-Line Peyot, Erik Joly, Stephanie Tobin, Stephanie Fulton, J Mark Brown, S R Murthy Madiraju, Marc Prentki
Suppression of α/β-domain hydrolase-6 (ABHD6), a monoacylglycerol (MAG) hydrolase, promotes glucose-stimulated insulin secretion by pancreatic β cells. We report here that high-fat-diet-fed ABHD6-KO mice show modestly reduced food intake, decreased body weight gain and glycemia, improved glucose tolerance and insulin sensitivity, and enhanced locomotor activity. ABHD6-KO mice also show increased energy expenditure, cold-induced thermogenesis, brown adipose UCP1 expression, fatty acid oxidation, and white adipose browning...
March 29, 2016: Cell Reports
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