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Cachexia and brown adipose tissue

Janina A Vaitkus, Francesco S Celi
Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning...
December 8, 2016: Experimental Biology and Medicine
S T Zhang, H M Yang
Cancer cachexia occurs in a majority of advanced cancer patients. These patients with impaired physical function are unable to tolerance cancer treatment well and have a significantly reduced survival rate. Currently, there is no effective clinical treatment available for cancer cachexia, therefore, it is necessary to clarify the molecular mechanisms of cancer cachexia, moreover, new therapeutic targets for cancer cachexia treatment are urgently needed. Very recent studies suggest that, during cancer cachexia, white adipose tissue undergo a 'browning' process, resulting in increased lipid mobilization and energy expenditure, which may be necessary for the occurrence of cancer cachexia...
August 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Diler Us Altay, E Edip Keha, Serap Ozer Yaman, Imran Ince, Ahmet Alver, Bahattin Erdogan, Sinan Canpolat, Umit Cobanoglu, Ahmet Mentese
BACKGROUND: The purpose of this study was to determine whether irisin is secreted by gastric tumor cells experimentally induced in mice, and also if it has any effect on cancer cachexia. DESIGN AND METHODS: 12 out of 60 BALB/c mice were used as a control group, while N-nitroso-N-methylurea (MNU) was administered orally to the remaining 48. After 150 days, the surviving mice were sacrificed by decapitation, blood and stomach, skeletal muscle, brown and white adipose tissue specimens were collected...
December 2016: QJM: Monthly Journal of the Association of Physicians
Amelia J Johnston, Nicholas J Hoogenraad
PURPOSE OF REVIEW: Although cancer cachexia is a very significant condition that is present in up to 80% of cancer cases, the cause of the condition has remained a puzzle. Cancer cachexia is a condition which is mainly characterised by muscle wasting, mobilization of fat reserves, and overall metabolic disturbance. This review aims to highlight some of the recent findings in cancer cachexia research. RECENT RESEARCH: It has been recently demonstrated that the expression of a single receptor, fibroblast growth factor-inducible 14, on a tumour can initiate cachexia and that this can be completely ablated by treatment with an antibody against this receptor...
July 2016: Current Opinion in Clinical Nutrition and Metabolic Care
Maria Tsoli, Michael M Swarbrick, Graham R Robertson
Although muscle wasting is the obvious manifestation of cancer cachexia that impacts on patient quality of life, the loss of lipid reserves and metabolic imbalance in adipose tissue also contribute to the devastating impact of cachexia. Depletion of fat depots in cancer patients is more pronounced than loss of muscle and often precedes, or even occurs in the absence of, reduced lean body mass. Rapid mobilisation of triglycerides stored within adipocytes to supply the body with fatty acids in periods of high-energy demand is normally mediated through a well-defined process of lipolysis involving the lipases ATGL, HSL and MGL...
June 2016: Seminars in Cell & Developmental Biology
Josep M Argilés, Britta Stemmler, Francisco J López-Soriano, Silvia Busquets
Cachexia is a syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting, and inflammation, being often associated with anorexia. In spite of the fact that muscle tissue represents more than 40% of body weight and seems to be the main tissue involved in the wasting that occurs during cachexia, recent developments suggest that tissues/organs such as adipose (both brown and white), brain, liver, gut, and heart are directly involved in the cachectic process and may be responsible for muscle wasting...
2015: Mediators of Inflammation
Kara L Kliewer, Jia-Yu Ke, Min Tian, Rachel M Cole, Rebecca R Andridge, Martha A Belury
Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia - before severe fat loss - in the colon-26 murine model of cachexia...
2015: Cancer Biology & Therapy
Katrin S Lindenberg, Patrick Weydt, Hans-Peter Müller, Axel Bornstedt, Albert C Ludolph, G Bernhard Landwehrmeyer, Wolfgang Rottbauer, Jan Kassubek, Volker Rasche
The recent discovery of active brown fat in human adults has led to renewed interest in the role of this key metabolic tissue. This is particularly true for neurodegenerative conditions like Huntington disease (HD), an adult-onset heritable disorder with a prominent energy deficit phenotype. Current methods for imaging brown adipose tissue (BAT) are in limited use because they are equipment-wise demanding and often prohibitively expensive. This prompted us to explore how a standard MRI set-up can be modified to visualize BAT in situ by taking advantage of its characteristic fat/water content ratio to differentiate it from surrounding white fat...
2014: PloS One
Judith de Vos-Geelen, Kenneth C H Fearon, Annemie M W Schols
PURPOSE OF REVIEW: To review new putative mechanisms involved in the pathophysiology of a disturbed energy balance in cancer cachexia, which can lead to novel targets for clinical cachexia management. In the context of rapid developments in tumour treatment with potential systemic consequences, this article reviews recent data on energy requirements. Furthermore, we focus on new insights in brown adipose tissue (BAT) activity and reward processing in the brain in relation to the cachexia process...
November 2014: Current Opinion in Clinical Nutrition and Metabolic Care
Michele Petruzzelli, Martina Schweiger, Renate Schreiber, Ramon Campos-Olivas, Maria Tsoli, John Allen, Michael Swarbrick, Stefan Rose-John, Mercedes Rincon, Graham Robertson, Rudolf Zechner, Erwin F Wagner
Cancer-associated cachexia (CAC) is a wasting syndrome characterized by systemic inflammation, body weight loss, atrophy of white adipose tissue (WAT) and skeletal muscle. Limited therapeutic options are available and the underlying mechanisms are poorly defined. Here we show that a phenotypic switch from WAT to brown fat, a phenomenon termed WAT browning, takes place in the initial stages of CAC, before skeletal muscle atrophy. WAT browning is associated with increased expression of uncoupling protein 1 (UCP1), which uncouples mitochondrial respiration toward thermogenesis instead of ATP synthesis, leading to increased lipid mobilization and energy expenditure in cachectic mice...
September 2, 2014: Cell Metabolism
Serkan Kir, James P White, Sandra Kleiner, Lawrence Kazak, Paul Cohen, Vickie E Baracos, Bruce M Spiegelman
Cachexia is a wasting disorder of adipose and skeletal muscle tissues that leads to profound weight loss and frailty. About half of all cancer patients suffer from cachexia, which impairs quality of life, limits cancer therapy and decreases survival. One key characteristic of cachexia is higher resting energy expenditure levels than in healthy individuals, which has been linked to greater thermogenesis by brown fat. How tumours induce brown fat activity is unknown. Here, using a Lewis lung carcinoma model of cancer cachexia, we show that tumour-derived parathyroid-hormone-related protein (PTHrP) has an important role in wasting, through driving the expression of genes involved in thermogenesis in adipose tissues...
September 4, 2014: Nature
Trupti Upadhye, Arun Gandhi, Sandip Basu
PURPOSE: To study the (18)F-FDG uptake pattern in brown adipose tissue (BAT) over an extended time period, by multiple-time-point fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. The primary objective for this kind of research was that it could form a basis and may have further implications for obesity research, metabolic diseases and for cachexia of both malignant and benign origin. METHODS: A total of 12 patients who had undergone routine FDG-PET for disease evaluation and had demonstrated prominent BAT uptake in their baseline scans were selected...
June 2013: Nuclear Medicine and Molecular Imaging
Matthias Bauwens, Roel Wierts, Bart van Royen, Jan Bucerius, Walter Backes, Felix Mottaghy, Boudewijn Brans
PURPOSE: Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. METHODS: This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted...
April 2014: European Journal of Nuclear Medicine and Molecular Imaging
Yulia Elkina, Sandra Palus, Anika Tschirner, Kai Hartmann, Stephan von Haehling, Wolfram Doehner, Ulrike Mayer, Andrew J S Coats, John Beadle, Stefan D Anker, Jochen Springer
BACKGROUND: Cancer cachexia is thought to be the cause of >20% of cancer related deaths. Symptoms of cancer cachexia patients include depression and anorexia significantly worsening their quality of life. Moreover, in rodent models of cancer cachexia atrophy of the heart has been shown to impair cardiac function. Here, we characterize the effects of the antidepressant and anxiolytic drug tandospirone on wasting, cardiac function and survival in experimental cancer cachexia. METHODS: The well-established Yoshida hepatoma rat model was used and tumor-bearing rats were treated with 1mg/kg/d (LD), 10mg/kg/d (HD) tandospirone or placebo...
December 10, 2013: International Journal of Cardiology
M Holubová, A Spolcová, Z Demianová, D Sýkora, J A Fehrentz, J Martinez, A Stofková, J Jurčovičová, J Drápalová, Z Lacinová, M Haluzík, B Zelezná, L Maletínská
Ghrelin and agonists of its receptor GHS-R1a are potential substances for the treatment of cachexia. In the present study, we investigated the acute and long term effects of the GHS R1a agonist JMV 1843 (H Aib-DTrp-D-gTrp-CHO) on food intake, body weight and metabolic parameters in lean C57BL/6 male mice. Additionally, we examined stability of JMV 1843 in mouse blood serum. A single subcutaneous injection of JMV 1843 (0.01-10 mg/kg) increased food intake in fed mice in a dose-dependent manner, up to 5-times relative to the saline-treated group (ED(50)=1...
2013: Physiological Research
Vicky Wang-Wei Tsai, Laurence Macia, Heiko Johnen, Tamara Kuffner, Rakesh Manadhar, Sebastian Beck Jørgensen, Ka Ki Michelle Lee-Ng, Hong Ping Zhang, Liyun Wu, Christopher Peter Marquis, Lele Jiang, Yasmin Husaini, Shu Lin, Herbert Herzog, David A Brown, Amanda Sainsbury, Samuel N Breit
The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1(-/-)) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1(-/-) mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass...
2013: PloS One
Aderville Cabassi, Stefano Tedeschi
PURPOSE OF REVIEW: Cachexia development is a feature of cancer as well as other chronic diseases. Fat mass loss appears of greatest importance in cachexia, as it is related to poorer survival. Zinc-α2-glycoprotein (ZAG), firstly isolated in human plasma 50 years ago, has emerged as a novel adipokine, which plays an important role in mobilization and utilization of lipids. This review will focus on recent evidences of ZAG as a fat catabolic marker in cancer and other diseases complicated by cachexia...
May 2013: Current Opinion in Clinical Nutrition and Metabolic Care
Gunjan Sinha
No abstract text is available yet for this article.
July 3, 2012: Journal of the National Cancer Institute
Maria Tsoli, Melissa Moore, Dominic Burg, Arran Painter, Ryland Taylor, Sarah H Lockie, Nigel Turner, Alessandra Warren, Greg Cooney, Brian Oldfield, Stephen Clarke, Graham Robertson
Cancer cachexia/anorexia is a complex syndrome that involves profound metabolic imbalances and is directly implicated as a cause of death in at least 20% to 30% of all cancers. Brown adipose tissue (BAT) plays a key role in thermogenesis and energy balance and potentially contributes to the physiologic perturbations associated with cachexia. In this study, we investigated the impact of cachexia-inducing colorectal tumor on BAT in mice. We found that brown adipocytes were smaller and exhibited profound delipidation in cachectic tumor-bearing mice...
September 1, 2012: Cancer Research
Anika Tschirner, Stephan von Haehling, Sandra Palus, Wolfram Doehner, Stefan D Anker, Jochen Springer
BACKGROUND: Cancer cachexia is characterized by loss of both adipose and skeletal muscle tissue and by an increased production of proinflammatory cytokines. Ursodeoxycholic acid (UDCA), a bile acid used for centuries in the treatment of liver disease, is known to confer anti-inflammatory and anti-apoptotic effects as well as beneficial effects on mitochondrial integrity and cell signaling. We hypothesized that UDCA ameliorates the wasting process in the Yoshida hepatoma tumor model. In addition, we sought to establish if UDCA exerts beneficial effects on survival in this model...
March 2012: Journal of Cachexia, Sarcopenia and Muscle
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