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https://www.readbyqxmd.com/read/29793055/fatty-acid-activation-in-thermogenic-adipose-tissue
#1
REVIEW
Sandra Steensels, Baran A Ersoy
Channeling carbohydrates and fatty acids to thermogenic tissues, including brown and beige adipocytes, have garnered interest as an approach for the management of obesity-related metabolic disorders. Mitochondrial fatty acid oxidation (β-oxidation) is crucial for the maintenance of thermogenesis. Upon cellular fatty acid uptake or following lipolysis from triglycerides (TG), fatty acids are esterified to coenzyme A (CoA) to form active acyl-CoA molecules. This enzymatic reaction is essential for their utilization in β-oxidation and thermogenesis...
May 21, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29787809/eet-enhances-renal-function-in-obese-mice-resulting-in-restoration-of-mfn1-2-ho-1-signaling-and-decrease-in-hypertension-through-inhibition-of-sodium-chloride-co-transporter
#2
Joseph Schragenheim, Lars Bellner, Jian Cao, Shailendra P Singh, David Bamshad, John A McClung, Omri Maayan, Aliza Meissner, Ilana Grant, Charles T Stier, Nader G Abraham
BACKGROUND: We have previously reported that epoxyeicosatrienoic acid (EET) has multiple beneficial effects on renal and adipose tissue function, in addition to its vasodilatory action; it increases insulin sensitivity and inhibits inflammation. In an examination of the signaling mechanisms by which EET reduces renal and peri-renal fat function, we hypothesized that EET ameliorates obesity-induced renal dysfunction by improving sodium excretion, reducing the sodium-chloride cotransporter NCC, lowering blood pressure, and enhancing mitochondrial and thermogenic gene levels in PGC-1α dependent mice...
May 19, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29787752/systemic-inhibition-of-janus-kinase-induces-browning-of-white-adipose-tissue-and-ameliorates-obesity-related-metabolic-disorders
#3
Kikid Rucira Qurania, Koji Ikeda, Donytra Arby Wardhana, Agian Jeffilano Barinda, Dhite Bayu Nugroho, Yuko Kuribayashi, Elda Putri Rahardini, Pranindya Rinastiti, Gusty Rizky Teguh Ryanto, Keiko Yagi, Ken-Ichi Hirata, Noriaki Emoto
Browning of white adipose tissue is a promising strategy to tackle obesity. Recently, Janus kinase (JAK) inhibition was shown to induce white-to-brown metabolic conversion of adipocytes in vitro; however effects of JAK inhibition on browning and systemic metabolic health in vivo remain to be elucidated. Here, we report that systemic administration of JAK inhibitor (JAKi) ameliorated obesity-related metabolic disorders. Administration of JAKi in mice fed a high-fat diet increased UCP-1 and PRDM16 expression in white adipose tissue, indicating the browning of white adipocyte...
May 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29785025/an-immune-beige-adipocyte-communication-via-nicotinic-acetylcholine-receptor-signaling
#4
Heejin Jun, Hui Yu, Jianke Gong, Juan Jiang, Xiaona Qiao, Eric Perkey, Dong-Il Kim, Margo P Emont, Alexander G Zestos, Jung-Sun Cho, Jianfeng Liu, Robert T Kennedy, Ivan Maillard, X Z Shawn Xu, Jun Wu
Beige adipocytes have recently been shown to regulate energy dissipation when activated and help organisms defend against hypothermia and obesity. Prior reports indicate that beige-like adipocytes exist in adult humans and that they may present novel opportunities to curb the global epidemic in obesity and metabolic illnesses. In an effort to identify unique features of activated beige adipocytes, we found that expression of the cholinergic receptor nicotinic alpha 2 subunit (Chrna2) was induced in subcutaneous fat during the activation of these cells and that acetylcholine-producing immune cells within this tissue regulated this signaling pathway via paracrine mechanisms...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29784793/camp-inducible-coactivator-crtc3-attenuates-brown-adipose-tissue-thermogenesis
#5
Young-Sil Yoon, Wen-Wei Tsai, Sam Van de Velde, Zhijiang Chen, Kuo-Fen Lee, Donald A Morgan, Kamal Rahmouni, Shigenobu Matsumura, Ezra Wiater, Youngsup Song, Marc Montminy
In response to cold exposure, placental mammals maintain body temperature by increasing sympathetic nerve activity in brown adipose tissue (BAT). Triggering of β-adrenergic receptors on brown adipocytes stimulates thermogenesis via induction of the cAMP/PKA pathway. Although cAMP response element-binding protein (CREB) and its coactivators-the cAMP-regulated transcriptional coactivators (CRTCs)-mediate transcriptional effects of cAMP in most tissues, other transcription factors such as ATF2 appear critical for induction of thermogenic genes by cAMP in BAT...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29763732/development-activation-and-therapeutic-potential-of-thermogenic-adipocytes
#6
REVIEW
Margo P Emont, Dong-Il Kim, Jun Wu
During the last decade, significant progress has been made in understanding adipocytes with a particular focus on thermogenic fat cells, which effectively convert chemical energy into heat in addition to their other metabolic functions. It has been increasingly recognized that different types and subtypes of adipocytes exist and the developmental origins of various types of fat cells are being intensively investigated. Previous work using immortalized fat cell lines has established an intricate transcriptional network that regulates adipocyte function...
May 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29757434/hdac3-selective-inhibition-activates-brown-and-beige-fat-through-prdm16
#7
Jiling Liao, Juan Jiang, Heejin Jun, Xiaona Qiao, Margo P Emont, Dong-Il Kim, Jun Wu
It has been reported that class I histone deacetylase (HDAC) inhibition increases thermogenesis in fat, but adipocyte specific Hdac3 deletions have presented inconsistent results. In this study, we observed that HDAC3 protein levels were lower in brown fat compared to that of inguinal subcutaneous adipose tissue, and were decreased in both fat depots upon cold exposure. PRDM16 physically interacted with HDAC3, and treatment with HDAC3-selective inhibitor RGFP966 induced thermogenic gene expression in murine and human fat cultures...
May 10, 2018: Endocrinology
https://www.readbyqxmd.com/read/29757365/multifaceted-roles-of-beige-fat-in-energy-homeostasis-beyond-ucp1
#8
Carlos Henrique Sponton, Shingo Kajimura
Beige adipocytes are an inducible form of thermogenic adipose cells that emerge within the white adipose tissue in response to a variety of environmental stimuli, such as chronic cold acclimation. Similar to brown adipocytes that reside in brown adipose tissue (BAT) depots, beige adipocytes are also thermogenic; however beige adipocytes possess unique, distinguishing characteristics in their developmental regulation and biological function. This review highlights recent advances in our understanding of beige adipocytes, focusing on the diverse roles of beige fat in the regulation of energy homeostasis that are independent of the canonical thermogenic pathway via uncoupling protein 1 (UCP1)...
May 10, 2018: Endocrinology
https://www.readbyqxmd.com/read/29756006/theoretical-model-and-characteristics-of-mitochondrial-thermogenesis
#9
Jian-Sheng Kang
Based on the first law of thermodynamics and the thermal diffusion equation, the deduced theoretical model of mitochondrial thermogenesis satisfies the Laplace equation and is a special case of the thermal diffusion equation. The model settles the long-standing question of the ability to increase cellular temperature by endogenous thermogenesis and explains the thermogenic characteristics of brown adipocytes. The model and calculations also suggest that the number of free available protons is the major limiting factor for endogenous thermogenesis and its speed...
2018: Biophysics Reports
https://www.readbyqxmd.com/read/29755411/time-of-day-effects-on-metabolic-and-clock-related-adjustments-to-cold
#10
Frederico Sander Mansur Machado, Zhi Zhang, Yan Su, Paul de Goede, Remi Jansen, Ewout Foppen, Cândido Celso Coimbra, Andries Kalsbeek
Background: Daily cyclic changes in environmental conditions are key signals for anticipatory and adaptive adjustments of most living species, including mammals. Lower ambient temperature stimulates the thermogenic activity of brown adipose tissue (BAT) and skeletal muscle. Given that the molecular components of the endogenous biological clock interact with thermal and metabolic mechanisms directly involved in the defense of body temperature, the present study evaluated the differential homeostatic responses to a cold stimulus at distinct time-windows of the light/dark-cycle...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29753771/mir-199a-3p-regulates-brown-adipocyte-differentiation-through-mtor-signaling-pathway
#11
Yao Gao, Yan Cao, Xianwei Cui, Xingyun Wang, Yahui Zhou, Fangyan Huang, Xing Wang, Juan Wen, Kaipeng Xie, Pengfei Xu, Xirong Guo, Lianghui You, Chenbo Ji
Recent discoveries of functional brown adipocytes in mammals illuminates their therapeutic potential for combating obesity and its associated diseases. However, on account of the limited amount and activity in adult humans of brown adipocyte depots, identification of miRNAs and characterization their regulatory roles in human brown adipogenesis are urgently needed. This study focused on the role of microRNA (miR)-199a-3p in human brown adipocyte differentiation and thermogenic capacity. A decreased expression pattern of miR-199a-3p was consistently observed during the differentiation course of brown adipocytes in mice and humans...
May 10, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29752068/tlr4-in-circumventricular-neural-stem-cells-is-a-negative-regulator-for-thermogenic-pathways-in-the-mouse-brain
#12
Shiori Muneoka, Saki Murayama, Yousuke Nakano, Seiji Miyata
Toll-like receptor 4 (TLR4) recognizes bacteria-derived lipopolysaccharide (LPS). In the present study, we found that intraperitoneal LPS activated nuclear factor-κ B (NF-κB) in TLR4-expressing neural stem cells (NSCs) in the circumventricular brain regions of mice. Intracerebroventricular preadministration of low-dose TLR4 inhibitors significantly augmented hyperthermia together with the inhibition of NF-κB activation in circumventricular NSCs of LPS-inflamed animals. Moreover, intracerebroventricular administration of high-dose TLR4 inhibitors induced hyperthermia and Fos activation in circumventricular NSCs and hypothalamic neurons...
May 3, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29750960/a-novel-role-for-ptk2b-in-cultured-beige-adipocyte-differentiation
#13
Bin Ni, Jared S Farrar, Shanshan Chen, Joseph C Lownik, Francesco S Celi
Adipocyte differentiation is a tightly regulated process which requires the sequential and organized expression of numerous genes and proteins. Phosphorylation of cytoplasmic proteins and key transcription factors represents a critical regulatory mechanism of the process leading to adipocyte maturation and modulation of associated metabolic pathways. Despite the recognition of the importance of protein phosphorylation in adipocyte biology, relatively little is known about the role of specific kinases in thermogenic (brown or beige) adipocyte differentiation and function...
May 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29748882/evolution-of-ucp1
#14
Michael J Gaudry, Kevin L Campbell, Martin Jastroch
Brown adipose tissue (BAT), the specialized heat-producing organ found in many placental mammals including humans, may be accessible for clinical drug intervention to help combat metabolic diseases. Understanding the biology of BAT and its thermogenic uncoupling protein 1 (UCP1) will benefit from an assessment of its evolution, answering where UCP1 originated and how it has been modified and integrated into cellular energy metabolism. Here, we review topical insights regarding the molecular evolution of UCP1-also reconstructing the proximate and ultimate factors selecting for brown fat thermogenesis in placental mammals...
May 10, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29727404/effects-of-p-synephrine-and-caffeine-ingestion-on-substrate-oxidation-during-exercise
#15
Jorge Gutiérrez-Hellín, Juan Del Coso
PURPOSE: Caffeine and p-synephrine are substances usually included in commercially-available products for weight loss because of their purported thermogenic effects. However, scientific information is lacking about the effects of combining these substances on substrate oxidation during exercise. The purpose of this investigation was to determine the isolated and combined effects of p-synephrine and caffeine on fat oxidation rate during exercise. METHODS: In a double-blind randomized experiment, 13 healthy subjects participated in 4 experimental trials after the ingestion of a capsule containing either a placebo, 3 mg·kg of caffeine, 3 mg·kg of p-synephrine, or the combination of these doses of caffeine and p-synephrine...
April 27, 2018: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/29719250/mitophagy-directs-muscle-adipose-crosstalk-to-alleviate-dietary-obesity
#16
Tingting Fu, Zhisheng Xu, Lin Liu, Qiqi Guo, Hao Wu, Xijun Liang, Danxia Zhou, Liwei Xiao, Lei Liu, Yong Liu, Min-Sheng Zhu, Quan Chen, Zhenji Gan
The quality of mitochondria in skeletal muscle is essential for maintaining metabolic homeostasis during adaptive stress responses. However, the precise control mechanism of muscle mitochondrial quality and its physiological impacts remain unclear. Here, we demonstrate that FUNDC1, a mediator of mitophagy, plays a critical role in controlling muscle mitochondrial quality as well as metabolic homeostasis. Skeletal-muscle-specific ablation of FUNDC1 in mice resulted in LC3-mediated mitophagy defect, leading to impaired mitochondrial energetics...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29719233/toward-an-understanding-of-how-immune-cells-control-brown-and-beige-adipobiology
#17
REVIEW
Francesc Villarroya, Rubén Cereijo, Joan Villarroya, Aleix Gavaldà-Navarro, Marta Giralt
Immune cells were recently found to have an unexpected involvement in controlling the thermogenic activity of brown and beige adipose tissue. Here, we review how macrophages, eosinophils, type 2 innate lymphoid cells, and T lymphocytes are linked to this process. In particular, the recruitment of alternatively activated macrophages and eosinophils is associated with brown fat activation and white fat browning. Conversely, pro-inflammatory immune cell recruitment represses the thermogenic activity of brown and beige adipose tissues via cytokines that inhibit noradrenergic signaling...
May 1, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29718003/brown-adipose-tissue-and-lipid-metabolism
#18
Joerg Heeren, Ludger Scheja
PURPOSE OF REVIEW: This article explores how the interplay between lipid metabolism and thermogenic adipose tissues enables proper physiological adaptation to cold environments in rodents and humans. RECENT FINDINGS: Cold exposure triggers systemic changes in lipid metabolism, which increases fatty acid delivery to brown adipose tissue (BAT) by various routes. Next to fatty acids generated intracellularly by de-novo lipogenesis or by lipolysis at lipid droplets, brown adipocytes utilize fatty acids released by white adipose tissue (WAT) for adaptive thermogenesis...
June 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29715048/%C3%AE-adrenergic-receptors-control-brown-adipose-ucp-1-tone-and-cold-response-without-affecting-its-circadian-rhythmicity
#19
Maria Razzoli, Matthew J Emmett, Mitchell A Lazar, Alessandro Bartolomucci
Brown adipose tissue (BAT) thermogenic functions are primarily mediated by uncoupling protein (UCP)-1. Ucp1 gene expression is highly induced by cold temperature, via sympathetic nervous system and β-adrenergic receptors (βARs). Ucp1 is also repressed by the clock gene Rev-erbα, contributing to its circadian rhythmicity. In this study, we investigated mice lacking βARs (β-less mice) to test the relationship between βAR signaling and the BAT molecular clock. We found that in addition to controlling the induction of Ucp1 and other key BAT genes at near freezing temperatures, βARs are essential for the basal expression of BAT Ucp1 at room temperature...
May 1, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29707604/cyp-450-epoxygenase-derived-epoxyeicosatrienoic-acid-contribute-to-reversal-of-heart-failure-in-obesity-induced-diabetic-cardiomyopathy-via-pgc-1-%C3%AE-activation
#20
S P Singh, J A McClung, L Bellner, J Cao, M Waldman, J Schragenheim, M Arad, E Hochhauser, J R Falck, J A Weingarten, S J Peterson, N G Abraham
We have previously shown that an Epoxyeicosatrienoic Acid (EET) -agonist has pleiotropic effects and reverses cardiomyopathy by decreasing inflammatory molecules and increasing antioxidant signaling. We hypothesized that administration of an EET agonist would increase Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), which controls mitochondrial function and induction of HO-1 and negatively regulates the expression of the proinflammatory adipokines CCN3/NOV in cardiac and pericardial tissues...
2018: Cardiovascular Pharmacology: Open Access
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