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Alexandre Caron, Denis Richard
With the still-growing prevalence of obesity worldwide, major efforts are made to understand the various behavioral, environmental, and genetic factors that promote excess fat gain. Obesity results from an imbalance between energy intake and energy expenditure, which emphasizes the importance of deciphering the mechanisms behind energy balance regulation to understand its physiopathology. The control of energy balance is assured by brain systems/circuits capable of generating adequate ingestive and thermogenic responses to maintain the stability of energy reserves, which implies a proper integration of the homeostatic signals that inform about the status of the energy stores...
October 21, 2016: Annals of the New York Academy of Sciences
Patrick C Even, Anne Blais
The components of energy expenditure, total metabolic rate (TMR), resting metabolic rate (RMR), thermogenic response to feeding (TEF), activity, and cost of activity were measured in fed and fasted mice housed at 22 and 30°C. Mice housed at 22°C had more than two times larger TMR and RMR. Mice at 22°C were less active when fasted but more active when fed. Cost of activity was nearly doubled in the fasted and in the fed state. Analysis of the short-term relation between TMR, RMR, and bouts of activity showed that, at 22°C, the bouts of activity induced a decrease in the intensity of RMR that reflected the reduced need for thermal regulation induced by the heat released from muscular contraction...
2016: Frontiers in Nutrition
Marin L Gantner, Bethany C Hazen, Elodie Eury, Erin L Brown, Anastasia Kralli
Brown adipose tissue (BAT) thermogenesis relies on a high abundance of mitochondria and the unique expression of the mitochondrial protein UCP1, which uncouples substrate oxidation from ATP synthesis. Adrenergic stimulation of brown adipocytes activates UCP1-mediated thermogenesis; it also induces the expression of Ucp1 and other genes important for thermogenesis, thereby endowing adipocytes with higher oxidative and uncoupling capacities. Adipocyte mitochondrial biogenesis and oxidative capacity are controlled by multiple transcription factors, including the estrogen-related receptor α (ERRα)...
October 20, 2016: Endocrinology
Martin Jastroch, Sylvain Giroud, Perry Barrett, Fritz Geiser, Gerhard Heldmaier, Annika Herwig
Endothermic mammals and birds require intensive energy turnover to sustain high body temperatures and metabolic rates. To cope with energetic bottlenecks associated with the change of seasons, and to minimise energy expenditure, complex mechanisms and strategies, such as daily torpor and hibernation, are used. During torpor metabolic depression and low body temperatures save energy. However, these bouts of torpor lasting for hours to weeks are interrupted by active 'euthermic' phases with high body temperatures...
October 18, 2016: Journal of Neuroendocrinology
Yuanting Cui, Li Li, Peng Gao, Liqun Ma, Daoyan Liu, Zhiming Zhu
OBJECTIVE: Obesity is global healthy problem. Uncoupling protein 1 (UCP1) mainly expresses on brown adipose tissue (BAT), uncouples energy substrate oxidation from mitochondrial ATP production and results in the loss of potential energy as heat. Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is the heat-gated cation ion channel. The aim of this study was to investigate the in vivo role of TRPV1 and UCP1 co-action in obesity. DESIGN AND METHOD: We generated and characterized UCP1 mice lacking TRPV1 activity (TRPV1/UCP1 mice)...
September 2016: Journal of Hypertension
Alina Gavrila, Per-Olof Hasselgren, Allison Glasgow, Ashley N Doyle, Alice Lee, Peter Fox, Gautam Shiva, James V Hennessey, Gerald M Kolodny, Aaron M Cypess
BACKGROUND: In addition to its role in adaptive thermogenesis, brown adipose tissue (BAT) may protect from weight gain, insulin resistance/diabetes and metabolic syndrome. Prior studies have shown contradictory results regarding the influence of thyroid hormone (TH) levels on BAT volume and activity. The aim of this pilot study was to gain further insight regarding the effect of TH treatment on BAT function in adult humans by evaluating the BAT mass and activity prospectively in six patients, first in the hypothyroid and then in the thyrotoxic phase...
October 17, 2016: Thyroid: Official Journal of the American Thyroid Association
L Dollet, J Magré, M Joubert, C Le May, A Ayer, L Arnaud, C Pecqueur, V Blouin, B Cariou, X Prieur
Loss-of-function mutations in BSCL2 are responsible for Berardinelli-Seip congenital lipodystrophy, a rare disorder characterized by near absence of adipose tissue associated with insulin resistance. Seipin-deficient (Bscl2(-/-)) mice display an almost total loss of white adipose tissue (WAT) with residual brown adipose tissue (BAT). Previous cellular studies have shown that seipin deficiency alters white adipocyte differentiation. In this study, we aimed to decipher the consequences of seipin deficiency in BAT...
October 17, 2016: Scientific Reports
Justin Darcy, Samuel McFadden, Yimin Fang, Joshua A Huber, Chi Zhang, Liou Y Sun, Andrzej Bartke
Ames dwarf mice (Prop1(df/df)) are long-lived due to a loss of function mutation resulting in deficiency of growth hormone (GH), thyroid-stimulating hormone and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption (VO2) and heat production, as well as a decrease in their respiratory quotient (RQ). Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature (Tco). Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (eWAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion...
October 14, 2016: Endocrinology
Md Abu Sayed, Yui Umekawa, Kikukatsu Ito
Skunk cabbage (Symplocarpus renifolius) blooms in early spring and its inflorescence, referred to as the spadix, can produce enough heat to melt snow. Here, we investigated glycolytic carbon flow at the PEP branch-point in thermogenic spadices. Our analyses revealed that petals and pistils in thermogenic florets exhibited higher expression of SrPEPC and SrAOX transcripts than those of SrPK, SrPEPCK, and SrPEPtase. Moreover, enzymatic analyses showed high activities of PEPC in the extracts from thermogenic florets...
October 14, 2016: Plant Signaling & Behavior
Manfred J Müller, Janna Enderle, Anja Bosy-Westphal
Metabolic adaptation to weight changes relates to body weight control, obesity and malnutrition. Adaptive thermogenesis (AT) refers to changes in resting and non-resting energy expenditure (REE and nREE) which are independent from changes in fat-free mass (FFM) and FFM composition. AT differs in response to changes in energy balance. With negative energy balance, AT is directed towards energy sparing. It relates to a reset of biological defence of body weight and mainly refers to REE. After weight loss, AT of nREE adds to weight maintenance...
October 13, 2016: Current Obesity Reports
Jonathan C Jun, Ronald Devera, Dileep Unnikrishnan, Mi-Kyung Shin, Shannon Bevans-Fonti, Qiaoling Yao, Aman Rathore, Haris Younas, Nils Halberg, Philipp E Scherer, Vsevolod Y Polotsky
: Hypoxia-inducible factor-1α (HIF-1α) in adipose tissue is known to promote obesity. We hypothesized that HIF-1α interferes with brown fat thermogenesis, thus decreasing energy expenditure. To test this hypothesis, we compared transgenic mice constitutively expressing HIF-1α in adipose tissues (HIF-1α++) at usual temperature (22 °C), where brown fat is somewhat active, or at thermoneutrality (30 °C), where brown fat is minimally active. HIF-1α++ mice or control litter mates were separated into room temperature (22 °C) or thermoneutrality (30 °C) groups...
October 14, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Peng Wang, Jianfei Sun, Zhichao Lou, Fengguo Fan, Ke Hu, Yi Sun, Ning Gu
Films of gold nanoparticles are easily fabricated by layer-by-layer assembly. With increasing number of layers a transition of the electric property from insulating to conducting can be achieved. This conductivity leads to controllable thermogenesis of the film, which can be employed for drug release of loaded hydrogels.
October 13, 2016: Advanced Materials
Ziye Xu, Jiaqi Liu, Tizhong Shan
Adipose tissues regulate energy metabolism and reproduction. There are three types of adipocytes (brown, white and beige adipocytes) in mammals. White adipocytes store energy and are closely associated with obesity and other metabolic diseases. The beige and brown adipocytes have numerous mitochondria and high levels of UCP1 that dissipates lipid to generate heat and defend against obesity. The global epidemic of obesity and its associated metabolic diseases urge an imperative need for understating the regulation of adipogenesis...
October 12, 2016: Journal of Cellular Physiology
Pasquina Marzola, Federico Boschi, Francesco Moneta, Andrea Sbarbati, Carlo Zancanaro
Localization, differentiation, and quantitative assessment of fat tissues have always collected the interest of researchers. Nowadays, these topics are even more relevant as obesity (the excess of fat tissue) is considered a real pathology requiring in some cases pharmacological and surgical approaches. Several weight loss medications, acting either on the metabolism or on the central nervous system, are currently under preclinical or clinical investigation. Animal models of obesity have been developed and are widely used in pharmaceutical research...
2016: Frontiers in Pharmacology
Xi-Ling Jiang, Hong-Wu Shen, Donald E Mager, Stephan Schmidt, Ai-Ming Yu
We have shown recently that concurrent harmaline, a monoamine oxidase-A inhibitor (MAOI), potentiates serotonin (5-HT) receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)-induced hyperthermia. The objective of this study was to develop an integrated pharmacokinetic/pharmacodynamic (PK/PD) model to characterize and predict the thermoregulatory effects of such serotonergic drugs in mice. Physiological thermoregulation was described by a mechanism-based indirect-response model with adaptive feedback control...
September 2016: Acta Pharmaceutica Sinica. B
Indumathi Chennamsetty, Michael Coronado, Kévin Contrepois, Mark P Keller, Ivan Carcamo-Orive, John Sandin, Giovanni Fajardo, Andrew J Whittle, Mohsen Fathzadeh, Michael Snyder, Gerald Reaven, Alan D Attie, Daniel Bernstein, Thomas Quertermous, Joshua W Knowles
We recently identified human N-acetyltransferase 2 (NAT2) as an insulin resistance (IR) gene. Here, we examine the cellular mechanism linking NAT2 to IR and find that Nat1 (mouse ortholog of NAT2) is co-regulated with key mitochondrial genes. RNAi-mediated silencing of Nat1 led to mitochondrial dysfunction characterized by increased intracellular reactive oxygen species and mitochondrial fragmentation as well as decreased mitochondrial membrane potential, biogenesis, mass, cellular respiration, and ATP generation...
October 4, 2016: Cell Reports
Qingzhang Zhu, Sarbani Ghoshal, Ana Rodrigues, Su Gao, Alice Asterian, Theodore M Kamenecka, James C Barrow, Anutosh Chakraborty
Enhancing energy expenditure (EE) is an attractive strategy to combat obesity and diabetes. Global deletion of Ip6k1 protects mice from diet-induced obesity (DIO) and insulin resistance, but the tissue-specific mechanism by which IP6K1 regulates body weight is unknown. Here, we have demonstrated that IP6K1 regulates fat accumulation by modulating AMPK-mediated adipocyte energy metabolism. Cold exposure led to downregulation of Ip6k1 in murine inguinal and retroperitoneal white adipose tissue (IWAT and RWAT) depots...
October 4, 2016: Journal of Clinical Investigation
Miguel López, Manuel Tena-Sempere
Ovarian steroids, such as estradiol (E2), control a vastness of physiological processes, such as puberty, reproduction, growth, development and metabolic rate. In fact, physiological, pathological, pharmacological or genetically-induced estrogen deficiency causes increased appetite and reduced energy expenditure, promoting weight gain and ultimately leading to obesity. Remarkably, estrogen replacement reverts those effects. Interestingly, although a wealth of evidence has shown that E2 can directly modulate peripheral tissues to exert their metabolic actions, novel data gathered in recent years have shown that those effects are mainly central and occur in the hypothalamus...
August 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
Audrey Sambeat, Olga Gulyaeva, Jon Dempersmier, Hei Sook Sul
In contrast to white adipose tissue (WAT), which stores energy in the form of triglycerides, brown adipose tissue (BAT) dissipates energy by producing heat to maintain body temperature by burning glucose and fatty acids in a process called adaptive thermogenesis. The presence of an inducible thermogenic adipose tissue, and its beneficial effects for maintaining body weight and glucose and lipid homeostasis, has raised intense interest in understanding the regulation of thermogenesis. Elucidating the regulatory mechanisms underlying the thermogenic adipose program may provide excellent targets for therapeutics against obesity and diabetes...
September 27, 2016: Trends in Endocrinology and Metabolism: TEM
Karl J Kaiyala, Kayoko Ogimoto, Jarrell T Nelson, Kenjiro Muta, Gregory J Morton
OBJECTIVE: To investigate the role played by leptin in thermoregulation, we studied the effects of physiological leptin replacement in leptin-deficient ob/ob mice on determinants of energy balance, thermogenesis and heat retention under 3 different ambient temperatures. METHODS: The effects of housing at 14 °C, 22 °C or 30 °C on core temperature (telemetry), energy expenditure (respirometry), thermal conductance, body composition, energy intake, and locomotor activity (beam breaks) were measured in ob/ob mice implanted subcutaneously with osmotic minipumps at a dose designed to deliver a physiological replacement dose of leptin or its vehicle-control...
October 2016: Molecular Metabolism
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