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https://www.readbyqxmd.com/read/28224045/dj-1-maintains-energy-and-glucose-homeostasis-by-regulating-the-function-of-brown-adipose-tissue
#1
Rong Wu, Xiao-Meng Liu, Jian-Guang Sun, Hong Chen, Jun Ma, Meng Dong, Shengyi Peng, Ji-Qiu Wang, Jian-Qing Ding, Dong-Hao Li, John R Speakman, Guang Ning, Wanzhu Jin, Zengqiang Yuan
DJ-1 protein is involved in multiple physiological processes, including Parkinson's disease. However, the role of DJ-1 in the metabolism is largely unknown. Here we found that DJ-1 maintained energy balance and glucose homeostasisvia regulating brown adipose tissue (BAT) activity. DJ-1-deficient mice reduced body mass, increased energy expenditure and improved insulin sensitivity. DJ-1 deletion also resisted high-fat-diet (HFD) induced obesity and insulin resistance. Accordingly, DJ-1 transgene triggered autonomous obesity and glucose intolerance...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28223503/mitochondrial-energy-deficiency-leads-to-hyperproliferation-of-skeletal-muscle-mitochondria-and-enhanced-insulin-sensitivity
#2
Ryan M Morrow, Martin Picard, Olga Derbeneva, Jeremy Leipzig, Meagan J McManus, Gilles Gouspillou, Sébastien Barbat-Artigas, Carlos Dos Santos, Russell T Hepple, Deborah G Murdock, Douglas C Wallace
Diabetes is associated with impaired glucose metabolism in the presence of excess insulin. Glucose and fatty acids provide reducing equivalents to mitochondria to generate energy, and studies have reported mitochondrial dysfunction in type II diabetes patients. If mitochondrial dysfunction can cause diabetes, then we hypothesized that increased mitochondrial metabolism should render animals resistant to diabetes. This was confirmed in mice in which the heart-muscle-brain adenine nucleotide translocator isoform 1 (ANT1) was inactivated...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223294/the-%C3%AE-3-adrenergic-receptor-is-dispensable-for-browning-of-adipose-tissues
#3
Jasper M A de Jong, René T F Wouters, Nathalie Boulet, Barbara Cannon, Jan Nedergaard, Natasa Petrovic
Brown and brite/beige adipocytes are attractive therapeutic targets to treat metabolic diseases. To maximally utilize their functional potential, further understanding is required about their identities and their functional differences. Recent studies with β3-adrenergic receptor knockout mice reported that brite/beige adipocytes, but not classical brown adipocytes, require the β3-adrenergic receptor for cold-induced transcriptional activation of thermogenic genes. We aimed to further characterize this requirement of the β3-adrenergic receptor as a functional distinction between classical brown and brite/beige adipocytes...
February 21, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28220393/common-and-distinct-regulation-of-human-and-mouse-brown-and-beige-adipose-tissues-a-promising-therapeutic-target-for-obesity
#4
REVIEW
Xuejiao Liu, Christopher Cervantes, Feng Liu
Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation...
February 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28218988/toxicological-effects-during-and-following-persistent-insulin-induced-hypoglycaemia-in-healthy-euglycaemic-rats
#5
Vivi F H Jensen, Anne-Marie Mølck, Line O Berthelsen, Lene Alifrangis, Lene Andersen, Melissa Chapman, Jens Lykkesfeldt, Ingrid B Bøgh
New insulin analogues with a longer duration of action and a "peakless" pharmacokinetic profile have been developed to improve efficacy, safety and convenience for diabetic patients. During non-clinical development, according to regulatory guidelines, these analogues are tested in healthy euglycaemic rats rendering them persistently hypoglycaemic. Little is known about the effect of persistent (24 hr/day) insulin-induced hypoglycaemia (IIH) in rats, complicating interpretation of results in pre-clinical studies with new longer-acting insulin analogues...
February 20, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28214707/shortcuts-to-a-functional-adipose-tissue-the-role-of-small-non-coding-rnas
#6
REVIEW
Bruna B Brandão, Beatriz A Guerra, Marcelo A Mori
Metabolic diseases such as type 2 diabetes are a major public health issue worldwide. These diseases are often linked to a dysfunctional adipose tissue. Fat is a large, heterogenic, pleiotropic and rather complex tissue. It is found in virtually all cavities of the human body, shows unique plasticity among tissues, and harbors many cell types in addition to its main functional unit - the adipocyte. Adipose tissue function varies depending on the localization of the fat depot, the cell composition of the tissue and the energy status of the organism...
February 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212318/alcohol-%C3%A2-adipose%C3%A2-tissue%C3%A2-and%C3%A2-lipid%C3%A2-dysregulation
#7
Jennifer L Steiner, Charles H Lang
Chronic alcohol consumption perturbs lipid metabolism as it increases adipose tissue lipolysis and leads to ectopic fat deposition within the liver and the development of alcoholic fatty liver disease. In addition to the recognition of the role of adipose tissue derived fatty acids in liver steatosis, alcohol also impacts other functions of adipose tissue and lipid metabolism. Lipid balance in response to long-term alcohol intake favors adipose tissue loss and fatty acid efflux as lipolysis is upregulated and lipogenesis is either slightly decreased or unchanged...
February 16, 2017: Biomolecules
https://www.readbyqxmd.com/read/28211512/physiology-and-role-of-irisin-in-glucose-homeostasis
#8
REVIEW
Nikolaos Perakakis, Georgios A Triantafyllou, José Manuel Fernández-Real, Joo Young Huh, Kyung Hee Park, Jochen Seufert, Christos S Mantzoros
Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Consequently, several studies attempted to characterize the role of irisin in glucose regulation, but contradictory results have been reported, and even the existence of this hormone has been questioned...
February 17, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28211464/molecular-basis-of-abhd5-lipolysis-activation
#9
Matthew A Sanders, Huamei Zhang, Ljiljana Mladenovic, Yan Yuan Tseng, James G Granneman
Alpha-beta hydrolase domain-containing 5 (ABHD5), the defective gene in human Chanarin-Dorfman syndrome, is a highly conserved regulator of adipose triglyceride lipase (ATGL)-mediated lipolysis that plays important roles in metabolism, tumor progression, viral replication, and skin barrier formation. The structural determinants of ABHD5 lipolysis activation, however, are unknown. We performed comparative evolutionary analysis and structural modeling of ABHD5 and ABHD4, a functionally distinct paralog that diverged from ABHD5 ~500 million years ago, to identify determinants of ABHD5 lipolysis activation...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209927/improved-health-span-and-lifespan-in-mtdna-mutator-mice-treated-with-the-mitochondrially-targeted-antioxidant-skq1
#10
Irina G Shabalina, Mikhail Yu Vyssokikh, Natalia Gibanova, Robert I Csikasz, Daniel Edgar, Anne Hallden-Waldemarson, Zinaida Rozhdestvenskaya, Lora E Bakeeva, Valeria B Vays, Antonina V Pustovidko, Maxim V Skulachev, Barbara Cannon, Vladimir P Skulachev, Jan Nedergaard
MtDNA mutator mice exhibit marked features of premature aging. We find that these mice treated from age of ≈100 days with the mitochondria-targeted antioxidant SkQ1 showed a delayed appearance of traits of aging such as kyphosis, alopecia, lowering of body temperature, body weight loss, as well as ameliorated heart, kidney and liver pathologies. These effects of SkQ1 are suggested to be related to an alleviation of the effects of an enhanced reactive oxygen species (ROS) level in mtDNA mutator mice: the increased mitochondrial ROS released due to mitochondrial mutations probably interact with polyunsaturated fatty acids in cardiolipin, releasing malondialdehyde and 4-hydroxynonenal that form protein adducts and thus diminishes mitochondrial functions...
February 15, 2017: Aging
https://www.readbyqxmd.com/read/28209760/glucoraphanin-ameliorates-obesity-and-insulin-resistance-through-adipose-tissue-browning-and-reduction-of-metabolic-endotoxemia-in-mice
#11
Naoto Nagata, Liang Xu, Susumu Kohno, Yusuke Ushida, Yudai Aoki, Ryohei Umeda, Nobuo Fuke, Fen Zhuge, Yinhua Ni, Mayumi Nagashimada, Chiaki Takahashi, Hiroyuki Suganuma, Shuichi Kaneko, Tsuguhito Ota
Low-grade sustained inflammation links obesity to insulin resistance and nonalcoholic fatty liver disease (NAFLD). However, therapeutic approaches to improve systemic energy balance and chronic inflammation in obesity are limited. Pharmacological activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) alleviates obesity and insulin resistance in mice; however, Nrf2 inducers are not clinically available owing to safety concerns. Thus, we examined whether dietary glucoraphanin, a stable precursor of the Nrf2 inducer sulforaphane, ameliorates systemic energy balance, chronic inflammation, insulin resistance, and NAFLD in high-fat diet (HFD)-fed mice...
February 16, 2017: Diabetes
https://www.readbyqxmd.com/read/28202906/bar502-a-dual-fxr-and-gpbar1-agonist-promotes-browning-of-white-adipose-tissue-and-reverses-liver-steatosis-and-fibrosis
#12
Adriana Carino, Sabrina Cipriani, Silvia Marchianò, Michele Biagioli, Chiara Santorelli, Annibale Donini, Angela Zampella, Maria Chiara Monti, Stefano Fiorucci
Non-alcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease. Here, we have investigated whether BAR502, a non-bile acid, steroidal dual ligand for FXR and GPBAR1, reverses steato-hepatitis in mice fed a high fat diet (HFD) and fructose. After 9 week, mice on HFD gained ≈30% of b.w (P < 0.01 versus naïve) and were insulin resistant. These overweighting and insulin resistant mice were randomized to receive HFD or HFD in combination with BAR502. After 18 weeks, HFD mice developed NASH like features with severe steato-hepatitis and fibrosis, increased hepatic content of triacylglycerol and cholesterol and expression of SREPB1c, FAS, ApoC2, PPARα and γ, α-SMA, α1 collagen and MCP1 mRNAs...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199304/adipose-derived-circulating-mirnas-regulate-gene-expression-in-other-tissues
#13
Thomas Thomou, Marcelo A Mori, Jonathan M Dreyfuss, Masahiro Konishi, Masaji Sakaguchi, Christian Wolfrum, Tata Nageswara Rao, Jonathon N Winnay, Ruben Garcia-Martin, Steven K Grinspoon, Phillip Gorden, C Ronald Kahn
Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue-brown especially-into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28196906/a-high-throughput-image-based-screen-to-identify-kinases-involved-in-brown-adipocyte-development
#14
Aliki Perdikari, Elisabeth Kulenkampff, Carla Rudigier, Heike Neubauer, Gerd Luippold, Norbert Redemann, Christian Wolfrum
Brown adipose tissue (BAT) is responsible for thermogenesis that is not associated with shivering through the process of converting chemical energy into heat through uncoupling protein 1 (UCP1) in the mitochondria. Thus, expanding or activating BAT could be a potential tool against obesity. To analyze the effect of kinase signaling on brown adipocyte formation, a process that describes the acquisition of the ability to dissipate energy as heat, we performed lentiviral-mediated short hairpin knockdown or used pharmacological inhibitors in a high-content and high-throughput in vitro image-based screen...
February 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28194257/is-p53-involved-in-tissue-specific-insulin-resistance-formation
#15
REVIEW
Justyna Strycharz, Jozef Drzewoski, Janusz Szemraj, Agnieszka Sliwinska
p53 constitutes an extremely versatile molecule, primarily involved in sensing the variety of cellular stresses. Functional p53 utilizes a plethora of mechanisms to protect cell from deleterious repercussions of genotoxic insults, where senescence deserves special attention. While the impressive amount of p53 roles has been perceived solely by the prism of antioncogenic effect, its presence seems to be vastly connected with metabolic abnormalities underlain by cellular aging, obesity, and inflammation. p53 has been found to regulate multiple biochemical processes such as glycolysis, oxidative phosphorylation, lipolysis, lipogenesis, β-oxidation, gluconeogenesis, and glycogen synthesis...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28194159/role-of-ucp1-gene-variants-in-interethnic-differences-in-the-development-of-cardio-metabolic-diseases
#16
Andreas D Flouris, Yulii V Shidlovskii, Alexander V Shaposhnikov, Levon Yepiskoposyan, Liliya Nadolnik, Lidia Karabon, Anna Kowalska, Andres E Carrillo, George S Metsios, Paraskevi Sakellariou
Cardio-metabolic diseases (CMDs) comprise a cluster of risk factors that contribute to chronic pathological conditions with adverse consequences for cardiovascular function and metabolic processes. A wide range of CMD prevalence rates among different ethnic groups has been documented. In view of accumulated evidence, there is a trend toward increasing CMD prevalence rates in Eastern Europe and Western Asia. Numerous studies have revealed an association between uncoupling protein 1 (UCP1) gene variants and CMDs...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28191637/mammary-alveolar-epithelial-cells-convert-to-brown-adipocytes-in-post-lactating-mice
#17
Antonio Giordano, Jessica Perugini, David M Kristensen, Loris Sartini, Andrea Frontini, Shingo Kajimura, Karsten Kristiansen, Saverio Cinti
During pregnancy and lactation, subcutaneous white adipocytes in the mouse mammary gland transdifferentiate reversibly to milk-secreting epithelial cells. In this study, we demonstrate by transmission electron microscopy that in the post-lactating mammary gland interscapular multilocular adipocytes found close to the mammary alveoli contain milk protein granules. Use of the Cre-loxP recombination system allowed showing that the involuting mammary gland of whey acidic protein-Cre/R26R mice, whose secretory alveolar cells express the lacZ gene during pregnancy, contains some X-Gal-stained and uncoupling protein 1-positive interscapular multilocular adipocytes...
February 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28187240/factors-involved-in-white-to-brown-adipose-tissue-conversion-and-in-thermogenesis-a-review
#18
REVIEW
T Montanari, N Pošćić, M Colitti
Obesity is the result of energy intake chronically exceeding energy expenditure. Classical treatments against obesity do not provide a satisfactory long-term outcome for the majority of patients. After the demonstration of functional brown adipose tissue in human adults, great effort is being devoted to develop therapies based on the adipose tissue itself, through the conversion of fat-accumulating white adipose tissue into energy-dissipating brown adipose tissue. Anti-obesity treatments that exploit endogenous, pharmacological and nutritional factors to drive such conversion are especially in demand...
February 10, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28186086/hoxc10-suppresses-browning-of-white-adipose-tissues
#19
Yvonne Ng, Shi-Xiong Tan, Sook Yoong Chia, Hwee Yim Angeline Tan, Sin Yee Gun, Lei Sun, Wanjin Hong, Weiping Han
Given that increased thermogenesis in white adipose tissue, also known as browning, promotes energy expenditure, significant efforts have been invested to determine the molecular factors involved in this process. Here we show that HOXC10, a homeobox domain-containing transcription factor expressed in subcutaneous white adipose tissue, is a suppressor of genes involved in browning white adipose tissue. Ectopic expression of HOXC10 in adipocytes suppresses brown fat genes, whereas the depletion of HOXC10 in adipocytes and myoblasts increases the expression of brown fat genes...
February 10, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28183451/the-novel-exercise-induced-hormone-irisin-protects-against-neuronal-injury-via-activation-of-the-akt-and-erk1-2-signaling-pathways-and-contributes-to-the-neuroprotection-of-physical-exercise-in-cerebral-ischemia
#20
Dong-Jie Li, Yong-Hua Li, Hong-Bin Yuan, Le-Feng Qu, Pei Wang
BACKGROUND: Irisin is a novel exercise-induced myokine involved in the regulation of adipose browning and thermogenesis. In this study, we investigated the potential role of irisin in cerebral ischemia and determined whether irisin is involved in the neuroprotective effect of physical exercise in mice. MATERIALS AND METHODS: The middle cerebral artery occlusion (MCAO) model was used to produce cerebral ischemia in mice. First, the plasma irisin levels and changes in expression of the irisin precursor protein FNDC5 in skeletal muscle were determined post ischemic stroke...
March 2017: Metabolism: Clinical and Experimental
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