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Brown adipose glucose tolerance

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https://www.readbyqxmd.com/read/27900258/adipocyte-specific-hypoxia-inducible-gene-2-promotes-fat-deposition-and-diet-induced-insulin-resistance
#1
Marina T DiStefano, Rachel J Roth Flach, Ozlem Senol-Cosar, Laura V Danai, Joseph V Virbasius, Sarah M Nicoloro, Juerg Straubhaar, Sezin Dagdeviren, Martin Wabitsch, Olga T Gupta, Jason K Kim, Michael P Czech
OBJECTIVE: Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis. METHOD: White and brown adipocyte-deficient (Hig2(fl/fl) × Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2(fl/fl) × Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27862843/elevated-circulating-neuregulin4-level-in-patients-with-diabetes
#2
Lu-Lu Chen, Miao-Miao Peng, Jiao-Yue Zhang, Xiang Hu, Jie Min, Qiu-Lan Huang, Li-Min Wan
BACKGROUND: Neuregulin4 is a novel adipokine expressed in adipose tissues, enriched in brown adipose tissue (BAT) and able to improve whole-body metabolism in rodent, thus having the potential to treat obesity-associated disorders such as diabetes. However, the association between serum Neuregulin4 levels and diabetes risk in human remains unclear. This study was designed to examine circulating Neuregulin4 levels in subjects with different glucose tolerance status. METHODS: Age-, sex- and BMI-matched subjects (n = 310: 83 normal glucose tolerance (NGT), 129 prediabetes and 96 diabetes) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal study (Reaction study) were included...
November 8, 2016: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/27832859/dietary-fat-drives-whole-body-insulin-resistance-and-promotes-intestinal-inflammation-independent-of-body-weight-gain
#3
Benjamin A H Jensen, Thomas S Nielsen, Andreas M Fritzen, Jacob B Holm, Even Fjære, Annette K Serup, Kamil Borkowski, Steve Risis, Simone I Pærregaard, Ida Søgaard, Audrey Poupeau, Michelle Poulsen, Tao Ma, Christian Sina, Bente Kiens, Lise Madsen, Karsten Kristiansen, Jonas T Treebak
BACKGROUND: The obesogenic potential of high-fat diets (HFD) in rodents is attenuated when the protein:carbohydrate ratio is increased. However, it is not known if intake of an HFD irrespective of the protein:carbohydrate ratio and in the absence of weight gain, affects glucose homeostasis and the gut microbiota. METHODS: We fed C57BL6/J mice 3 different HFDs with decreasing protein:carbohydrate ratios for 8weeks and compared the results to a LFD reference group...
December 2016: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27814392/gender-specific-mechanisms-underlying-the-amelioration-of-high-fat-diet-induced-glucose-intolerance-in-b-cell-activating-factor-deficient-mice
#4
Bobae Kim, Chang-Kee Hyun
It has recently been found that B cell activating factor (BAFF) plays an important role in the regulation of energy homeostasis. We also have previously reported that BAFF deficiency reverses high-fat (HF) diet-induced glucose intolerance by potentiating adipose tissue function. In the present study, we found that BAFF deficient (BAFF-/-) mice exhibit gender-specific differences in protection against diet-induced glucose intolerance, and aimed to characterize the gender-dependent molecular alterations in energy metabolism...
2016: PloS One
https://www.readbyqxmd.com/read/27804232/obeticholic-acid-improves-adipose-morphometry-and-inflammation-and-reduces-steatosis-in-dietary-but-not-metabolic-obesity-in-mice
#5
Fahrettin Haczeyni, Laurence Poekes, Hans Wang, Auvro R Mridha, Vanessa Barn, W Geoffrey Haigh, George N Ioannou, Matthew M Yeh, Isabelle A Leclercq, Narcissus C Teoh, Geoffrey C Farrell
OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is the outcome of interactions between overnutrition, energy metabolism, and adipose function. Obeticholic acid (OCA) improves steatosis in patients but for unknown reasons does not resolve NASH pathology. This study therefore investigated OCA effects in Wt mice, which develop obesity with atherogenic dietary feeding, and appetite-dysregulated, Alms1 mutant foz/foz mice fed the same diet, which develop metabolic obesity and diabetes. METHODS: OCA (1 mg/kg) was administered orally to female foz/foz mice and Wt littermates from weaning until 28 weeks...
November 2, 2016: Obesity
https://www.readbyqxmd.com/read/27803297/defective-adaptive-thermogenesis-contributes-to-metabolic-syndrome-and-liver-steatosis-in-obese-mice
#6
Laurence Poekes, Vanessa Legry, Olivier Schakman, Christine Detrembleur, Anne Bol, Yves Horsmans, Geoffrey C Farrell, Isabelle A Leclercq
Fatty liver diseases are complications of the metabolic syndrome associated with obesity, insulin resistance and low grade inflammation. Our aim was to uncover mechanisms contributing to hepatic complications in this setting. We used foz/foz mice prone to obesity, insulin resistance and progressive fibrosing NASH. Foz/foz mice are hyperphagic but WT-matched calorie intake failed to protect against obesity, adipose inflammation and glucose intolerance. Obese foz/foz mice had similar physical activity level but reduced energy expenditure...
November 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27795551/attenuation-of-diet-induced-obesity-and-induction-of-white-fat-browning-with-a-chemical-inhibitor-of-histone-deacetylases
#7
A Ferrari, E Fiorino, R Longo, S Barilla, N Mitro, G Cermenati, M Giudici, D Caruso, A Mai, U Guerrini, E De Fabiani, M Crestani
BACKGROUND/OBJECTIVES: In the last decade a strict link between epigenetics and metabolism has been demonstrated. Histone deacetylases (HDACs) have emerged as key epigenetic regulators involved in metabolic homeostasis in normal and pathologic conditions. Here we investigated the effect of the class I HDAC inhibitor MS-275 in a model of obesity induced by a high fat diet (HFD). METHODS: C57BL6/J male mice were fed HFD for 17 weeks and then randomized in two groups treated intraperitoneally with vehicle (DMSO) or with the class I selective HDAC inhibitor MS-275 every other day for 22 days...
October 31, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27699262/increased-apoptosis-and-browning-of-tak1-deficient-adipocytes-protects-against-obesity
#8
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
https://www.readbyqxmd.com/read/27695946/browning-of-subcutaneous-fat-and-higher-surface-temperature-in-response-to-phenotype-selection-for-advanced-endurance-exercise-performance-in-male-duhtp-mice
#9
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
https://www.readbyqxmd.com/read/27554471/salsalate-salicylate-uncouples-mitochondria-improves-glucose-homeostasis-and-reduces-liver-lipids-independent-of-ampk-%C3%AE-1
#10
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
https://www.readbyqxmd.com/read/27547848/endog-knockout-mice-show-increased-brown-adipocyte-recruitment-in-white-adipose-tissue-and-improved-glucose-homeostasis
#11
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
https://www.readbyqxmd.com/read/27461402/lkb1-controls-brown-adipose-tissue-growth-and-thermogenesis-by-regulating-the-intracellular-localization-of-crtc3
#12
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
https://www.readbyqxmd.com/read/27442117/fkbp51-null-mice-are-resistant-to-diet-induced-obesity-and-the-ppar%C3%AE-agonist-rosiglitazone
#13
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
https://www.readbyqxmd.com/read/27411515/rock1-reduces-mitochondrial-content-and-irisin-production-in-muscle-suppressing-adipocyte-browning-and-impairing-insulin-sensitivity
#14
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
https://www.readbyqxmd.com/read/27378359/uncoupling-mitochondrial-respiration-for-diabesity
#15
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
https://www.readbyqxmd.com/read/27340502/ppargc1%C3%AE-gene-dna-methylation-variations-in-human-placenta-mediate-the-link-between-maternal-hyperglycemia-and-leptin-levels-in-newborns
#16
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
https://www.readbyqxmd.com/read/27340128/activation-of-bile-acid-signaling-improves-metabolic-phenotypes-in-high-fat-diet-induced-obese-mice
#17
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
https://www.readbyqxmd.com/read/27294611/adipocyte-specific-deletion-of-mtor-inhibits-adipose-tissue-development-and-causes-insulin-resistance-in-mice
#18
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
https://www.readbyqxmd.com/read/27281802/a-daily-snack-containing-leafy-green-vegetables-fruit-and-milk-before-and-during-pregnancy-prevents-gestational-diabetes-in-a-randomized-controlled-trial-in-mumbai-india
#19
REVIEW
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
https://www.readbyqxmd.com/read/27242533/the-mechanism-by-which-safflower-yellow-decreases-body-fat-mass-and-improves-insulin-sensitivity-in-hfd-induced-obese-mice
#20
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
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