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https://www.readbyqxmd.com/read/27876809/cold-induced-thermogenesis-in-humans
#1
REVIEW
R J Brychta, K Y Chen
A basic property of endothermic thermoregulation is the ability to generate heat by increasing metabolism in response to cold ambient temperatures to maintain a stable core body temperature. This process, known as cold-induced thermogenesis (CIT), has been measured in humans as early as 1780 by Antoine Lavoisier, but has found renewed interest because of the recent 'rediscovery' of thermogenic, cold-activated brown adipose tissue (BAT) in adult humans. In this review, we summarize some of the key findings of the work involving CIT over the past two centuries and highlight some of the seminal studies focused on this topic...
November 23, 2016: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/27803297/defective-adaptive-thermogenesis-contributes-to-metabolic-syndrome-and-liver-steatosis-in-obese-mice
#2
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/27783937/%C3%AE-%C3%AE-hydrolase-domain-6-in-the-ventromedial-hypothalamus-controls-energy-metabolism-flexibility
#3
Alexandre Fisette, Stephanie Tobin, Léa Décarie-Spain, Khalil Bouyakdan, Marie-Line Peyot, S R Murthy Madiraju, Marc Prentki, Stephanie Fulton, Thierry Alquier
α/β-Hydrolase domain 6 (ABHD6) is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG). Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMH(KO)) have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27763777/complementary-roles-of-estrogen-related-receptors-in-brown-adipocyte-thermogenic-function
#4
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 Uncoupling Protein 1 (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 (ERR)α...
December 2016: Endocrinology
https://www.readbyqxmd.com/read/27750020/variable-cold-induced-brown-adipose-tissue-response-to-thyroid-hormone-status
#5
Alina Gavrila, Per-Olof Hasselgren, Allison Glasgow, Ashley N Doyle, Alice J Lee, Peter Fox, Shiva Gautam, 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 insights 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...
November 29, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27748422/seipin-deficiency-alters-brown-adipose-tissue-thermogenesis-and-insulin-sensitivity-in-a-non-cell-autonomous-mode
#6
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
https://www.readbyqxmd.com/read/27738746/adipose-hif-1%C3%AE-causes-obesity-by-suppressing-brown-adipose-tissue-thermogenesis
#7
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"
https://www.readbyqxmd.com/read/27701146/adipocyte-specific-deletion-of-ip6k1-reduces-diet-induced-obesity-by-enhancing-ampk-mediated-thermogenesis
#8
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...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27689002/physiological-role-for-leptin-in-the-control-of-thermal-conductance
#9
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
https://www.readbyqxmd.com/read/27672060/disruption-of-beta3-adrenergic-receptor-increases-susceptibility-to-dio-in-mouse
#10
Nailliw Z Preite, Bruna P P Nascimento, Cynthia R Muller, Anna Laura V Americo, Talita S Higa, Fabiana S Evangelista, Carmen L Lancellotti, Felipe Dos Santos Henriques, Miguel Luiz Batista Júnior, Antonio C Bianco, Miriam Oliveira Ribeiro
The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system (SNS) through β-adrenergic receptors (AR). Here we wished to define the role played by the ARβ3 isoform in this process. This study focused on the ARβ3 knockout mice (ARβ3KO), including responsiveness to cold exposure, diet-induced obesity, intolerance to glucose, dyslipidemia and lipolysis in white adipose tissue (WAT). ARβ3KO mice defend core temperature during cold exposure (4ºC for 5h), with faster BAT thermal response to Norepinephrine (NE) infusion when compared to wild-type (WT) mice...
September 26, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27647490/the-complementary-and-divergent-roles-of-uncoupling-proteins-1-and-3-in-thermoregulation
#11
Christopher L Riley, Christine Dao, M Alexander Kenaston, Luigina Muto, Shohei Kohno, Sara M Nowinski, Ashley D Solmonson, Matthew Pfeiffer, Michael N Sack, Zhongping Lu, Giuseppe Fiermonte, Jon E Sprague, Edward M Mills
KEY POINTS: Both uncoupling protein 1 (UCP1) and UCP3 are important for mammalian thermoregulation. UCP1 and UCP3 in brown adipose tissue mediate early and late phases of sympathomimetic thermogenesis, respectively. Lipopolysaccharide thermogenesis requires skeletal muscle UCP3 but not UCP1. Acute noradrenaline-induced hyperthermia requires UCP1 but not UCP3. Loss of both UCP1 and UCP3 accelerate the loss of body temperature compared to UCP1KO alone during acute cold exposure. ABSTRACT: Uncoupling protein 1 (UCP1) is the established mediator of brown adipose tissue-dependent thermogenesis...
September 20, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27622583/ucp1-protein-the-molecular-hub-of-adipose-organ-plasticity
#12
Saverio Cinti
In all mammals, adipocytes are cells with abundant cytoplasmic lipids forming the parenchyma of the adipose organ. White adipocytes store highly energetic molecules to release them, in the form of free fatty acids to survive between meals. Brown adipocytes trough their unique mitochondrial UCP1 protein burn glucose and lipids to perform thermogenesis in order to survive in cold environments. A third type of adipocytes appears in the subcutaneous depot of the adipose organ of female mice during pregnancy and lactation: the pink adipocytes...
September 10, 2016: Biochimie
https://www.readbyqxmd.com/read/27621146/origins-and-early-development-of-the-concept-that-brown-adipose-tissue-thermogenesis-is-linked-to-energy-balance-and-obesity
#13
Paul Trayhurn
Brown adipose tissue (BAT) was identified as a thermogenic organ in 1961, and in 1978 shown to be the major site of thermoregulatory non-shivering thermogenesis in rats acclimated to the cold. Investigations in the mid-late 1970s established the uncoupling of oxidative phosphorylation through a proton conductance pathway across the mitochondrial inner membrane as the mechanism for heat production in BAT, this being regulated by UCP1 which was first discovered as a 32,000 Mr cold-inducible protein. These developments came when those concerned with nutritional energetics were proposing that thermogenesis is a significant factor in energy balance and the aetiology of obesity...
September 10, 2016: Biochimie
https://www.readbyqxmd.com/read/27566776/lysine-specific-demethylase-1-promotes-brown-adipose-tissue-thermogenesis-via-repressing-glucocorticoid-activation
#14
Xing Zeng, Mark P Jedrychowski, Yi Chen, Sara Serag, Gareth G Lavery, Steve P Gygi, Bruce M Spiegelman
Brown adipocytes display phenotypic plasticity, as they can switch between the active states of fatty acid oxidation and energy dissipation versus a more dormant state. Cold exposure or β-adrenergic stimulation favors the active thermogenic state, whereas sympathetic denervation or glucocorticoid administration promotes more lipid accumulation. Our understanding of the molecular mechanisms underlying these switches is incomplete. Here we found that LSD1 (lysine-specific demethylase 1), a histone demethylase, regulates brown adipocyte metabolism in two ways...
August 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27560796/continuous-cold-exposure-induces-an-anti-inflammatory-response-in-mesenteric-adipose-tissue-associated-with-catecholamine-production-and-thermogenin-expression-in-rats
#15
P Vargovic, G Manz, R Kvetnansky
OBJECTIVE: Continuous exposure to cold leads to an activation of adaptive thermogenesis in the brown adipose tissue and induction of brown/beige cell phenotype in the white adipose tissue. Thermogenic response is associated with alternatively activated macrophages producing catecholamines, which subsequently activate the uncoupling protein 1 (UCP-1). The aim of this work was to elucidate the effect of cold exposure on catecholamine and immune responses associated with adipocyte browning in the mesenteric adipose tissue (mWAT) of rat...
July 2016: Endocrine Regulations
https://www.readbyqxmd.com/read/27554470/adipose-specific-deficiency-of-fumarate-hydratase-in-mice-protects-against-obesity-hepatic-steatosis-and-insulin-resistance
#16
Hao Yang, Jiang W Wu, Shu P Wang, Ilenia Severi, Loris Sartini, Norma Frizzell, Saverio Cinti, Gongshe Yang, Grant A Mitchell
Obesity and type 2 diabetes are associated with impaired mitochondrial function in adipose tissue. To study the effects of primary deficiency of mitochondrial energy metabolism in fat, we generated mice with adipose-specific deficiency of fumarate hydratase (FH), an integral Krebs cycle enzyme (AFHKO mice). AFHKO mice have severe ultrastructural abnormalities of mitochondria, ATP depletion in white and brown adipose tissues (WAT, BAT), low WAT mass with small adipocytes and impaired thermogenesis with large unilocular brown adipocytes...
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
#17
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/27492130/endothelial-pdgf-cc-regulates-angiogenesis-dependent-thermogenesis-in-beige-fat
#18
Takahiro Seki, Kayoko Hosaka, Sharon Lim, Carina Fischer, Jennifer Honek, Yunlong Yang, Patrik Andersson, Masaki Nakamura, Erik Näslund, Seppo Ylä-Herttuala, Meili Sun, Hideki Iwamoto, Xuri Li, Yizhi Liu, Nilesh J Samani, Yihai Cao
Cold- and β3-adrenoceptor agonist-induced sympathetic activation leads to angiogenesis and UCP1-dependent thermogenesis in mouse brown and white adipose tissues. Here we show that endothelial production of PDGF-CC during white adipose tissue (WAT) angiogenesis regulates WAT browning. We find that genetic deletion of endothelial VEGFR2, knockout of the Pdgf-c gene or pharmacological blockade of PDGFR-α impair the WAT-beige transition. We further show that PDGF-CC stimulation upregulates UCP1 expression and acquisition of a beige phenotype in differentiated mouse WAT-PDGFR-α(+) progenitor cells, as well as in human WAT-PDGFR-α(+) adipocytes, supporting the physiological relevance of our findings...
2016: Nature Communications
https://www.readbyqxmd.com/read/27489163/eicosapentaenoic-acid-potentiates-brown-thermogenesis-through-ffar4-dependent-up-regulation-of-mir-30b-and-mir-378
#19
Jiyoung Kim, Meshail Okla, Anjeza Erickson, Timothy Carr, Sathish Kumar Natarajan, Soonkyu Chung
Emerging evidence suggests that n-3 polyunsaturated fatty acids (PUFA) promote brown adipose tissue thermogenesis. However, the underlying mechanisms remain elusive. Here, we hypothesize that n-3 PUFA promotes brown adipogenesis by modulating miRNAs. To test this hypothesis, murine brown preadipocytes were induced to differentiate the fatty acids of palmitic, oleate, or eicosapentaenoic acid (EPA). The increases of brown-specific signature genes and oxygen consumption rate by EPA were concurrent with up-regulation of miR-30b and 378 but not by oleate or palmitic acid...
September 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27454177/regulation-of-brown-and-white-adipocyte-transcriptome-by-the-transcriptional-coactivator-nt-pgc-1%C3%AE
#20
Jihyun Kim, Vivian E Fernand, Tara M Henagan, Jeho Shin, Peter Huypens, Susan Newman, Thomas W Gettys, Ji Suk Chang
The β3-adrenergic receptor (AR) signaling pathway is a major component of adaptive thermogenesis in brown and white adipose tissue during cold acclimation. The β3-AR signaling highly induces the expression of transcriptional coactivator PGC-1α and its splice variant N-terminal (NT)-PGC-1α, which in turn activate the transcription program of adaptive thermogenesis by co-activating a number of transcription factors. We previously reported that NT-PGC-1α is able to increase mitochondrial number and activity in cultured brown adipocytes by promoting the expression of mitochondrial and thermogenic genes...
2016: PloS One
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