EDITOR'S PICK: Brown fat burns calories in adult humans
Brown adipose tissue (often known as brown fat) is a specialized tissue that burns calories to generate body heat in rodents and newborn humans, neither of which shiver. Recently, adult humans have also been found to possess brown fat. This fact piqued the interest of researchers seeking to combat the obesity epidemic, the thought being that if they could develop ways to increase the amount of brown fat a person has that person will become slimmer. One hitch to this idea is it has never actually been shown definitively that brown fat in adult humans can burn energy. Now, a team of researchers — led by André C. Carpentier, at Université de Sherbrooke, Sherbrooke, Quebec; and Denis Richard, at Université Laval, Quebec City, Quebec — has provided this evidence, showing that when healthy adult men are exposed to cold their brown fat burns energy to generate body heat. However, it did not burn energy at warm temperatures.
As Barbara Cannon and Jan Nedergaard, at Stockholm University, Sweden, discuss in an accompanying commentary, these data have significant implications for the human obesity epidemic. In particular, they note that the data generated by Carpentier, Richard, and colleagues indicates that developing ways to increase the amount of brown fat a person has is unlikely to make that person slimmer, what is needed is a way to make sure that the brown fat is active and burns calories.
TITLE: Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans
AUTHOR CONTACT:
André C. Carpentier
Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Quebec, Canada.
Phone: 819-564-5244; Fax: 819-564-5292; E-mail: andre.carpentier@usherbrooke.ca.
Denis Richard
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, Québec, Canada.
Phone: 418-656-8711, ext. 11714; Fax: 418-656-4929; E-mail: Denis.Richard@criucpq.ulaval.ca.
View this article at:
http://www.jci.org/articles/view/60433?key=5e3684aee3d55b74adc8
ACCOMPANYING COMMENTARY
TITLE: Yes, even human brown fat is on fire!
AUTHOR CONTACT:
Barbara Cannon
The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Phone: 46-8-164120; Fax: 46-8-156756; E-mail:
barbara.cannon@wgi.su.se.
View this article at:
http://www.jci.org/articles/view/60941?key=3723d9632a23d4529001
EDITOR'S PICK: Therapeutically useful stem cell derivatives in need of stability
Human stem cells capable of giving rise to any fetal or adult cell type are known as pluripotent stem cells. It is hoped that such cells, the most well known being human embryonic stem cells (hESCs), can be used to generate cell populations with therapeutic utility. In this context, neural derivatives of hESCs are being tested in clinical trials. However, Natalie Lefort and colleagues, at the Institute for Stem cell Therapy and Exploration of Monogenic diseases, France, have now generated cautionary data that suggest that additional quality controls need to be put in place to ensure that neural derivatives of human pluripotent stem cells are not genomically unstable, a common characteristic of cancer cells.
The key observation of Lefort and colleagues was that neural derivatives of human pluripotent stem cells frequently acquire extra material from chromosome 1q. Worryingly, this chromosomal defect has been associated with some blood cell cancers and pediatric brain tumors with poor clinical outcome, although Lefort and colleagues found that the abnormal neural cells they detected were unable to form tumors in mice.
As noted by Neil Harrison, at the University of Sheffield, United Kingdom, in an accompanying commentary, while the data raise safety issues relevant for the therapeutic use of these cells, the fact that the same chromosome was affected in all cases suggests that it should be possible to design screening strategies to detect and remove these cells.
TITLE: Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells
AUTHOR CONTACT:
Nathalie Lefort
INSERM/UEVE UMR-861, Institute for Stem cell Therapy and Exploration of Monogenic diseases, Evry, France.
Phone: 33169908517; Fax: 33169908521; E-mail: nlefort@istem.fr.
View this article at: http://www.jci.org/articles/view/46268?key=426c3974a389bf8a06a9
ACCOMPANYING COMMENTARY
TITLE: Genetic instability in neural stem cells: an inconvenient truth?
AUTHOR CONTACT:
Neil J. Harrison
University of Sheffield, Sheffield, United Kingdom.
Phone: 44-114-222-2313; Fax: 44-114-222-2399; E-mail: N.J.Harrison@sheffield.ac.uk.
View this article at:
http://www.jci.org/articles/view/62002?key=cfc5cea3e8bef101c4ed
NEPHROLOGY: Understanding acute kidney injury to identify potential therapeutics
Acute kidney injury (AKI) is a life-threatening condition that frequently complicates the care of hospitalized patients. There are no specific therapies to treat AKI other than kidney replacement therapies such as dialysis. Better understanding of the molecular mechanisms underlying AKI is needed if effective new therapies are to be developed. In this context, a team of researchers led by Holger Eltzschig, at the University of Colorado Denver, Aurora, has now dissected the role of the molecule adenosine in mice exposed to AKI caused by transient obstruction to the blood flow to the kidney, the most common cause of AKI in patients. In doing so, Eltzschig and colleagues identified activators of the A2B adenosine receptor and inhibitors of the protein ENT1, which is involved in transporting adenosine into and out of cells in the kidney, as potential therapeutics for AKI, although they caution that mice are not humans and that much work is needed to see if their results in mice hold up in humans.
In an accompanying commentary, Joel Weinberg (at the University of Michigan, Ann Arbor) and Manjeri A. Venkatachalam (at University of Texas Health Science Center at San Antonio, San Antonio) discuss the complexities of the work performed by Eltzschig and colleagues and the relevance of the data to the human condition.
TITLE: Equilibrative nucleoside transporter 1 (ENT1) regulates postischemic blood flow during acute kidney injury in mice
AUTHOR CONTACT:
Holger K. Eltzschig
University of Colorado Denver, Aurora, Colorado, USA.
Phone: 303-724-2931; Fax: 303-724-2936; E-mail: holger.eltzschig@ucdenver.edu.
View this article at:
http://www.jci.org/articles/view/60214?key=08d041baa97863b6dc1d
ACCOMPANYING COMMENTARY
TITLE: Preserving postischemic reperfusion in the kidney: a role for extracellular adenosine
AUTHOR CONTACT:
Joel M. Weinberg
University of Michigan, Ann Arbor, Michigan, USA.
Phone: 734-764-3157; Fax: 734-763-0982; E-mail: wnberg@umich.edu.
View this article at: http://www.jci.org/articles/view/60957?key=80692b200000946d601d
VASCULAR DISEASE: Triple A rating for gene regulatory molecule miR-29b
Abdominal aortic aneurysms (AAAs) are an abnormal widening or ballooning of the lower part of the body's main artery (the aorta) due to weakness in its wall. They are a common clinical condition, occurring primarily in men over the age of 65 years, that can cause death due to dissection or rupture of the aorta at the site of the aneurysm. Treatment depends on the size of the aneurysm at diagnosis — patients with small aneurysms are treated using a watch-and-wait approach while those with large aneurysms require surgery. A team of researchers led by Philip Tsao, at Stanford University School of Medicine, Stanford, has now generated data in two mouse models of AAA that suggest that manipulating levels of the gene regulatory molecule miR-29b and the levels of the genes it regulates could help limit AAA progression and protect from rupture.
In an accompanying commentary, Dianna Milewicz, at The University of Texas Health Science Center at Houston, Houston, discusses the data generated by Tsao and colleagues in light of other recent work investigating the role of miR-29 in aortic aneurysm formation.
TITLE: Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development
AUTHOR CONTACT:
Philip S. Tsao
Stanford University School of Medicine, Stanford, California, USA.
Phone: 650-498-6317; Fax: 650-725-2178; E-mail: ptsao@stanford.edu.
View this article at:
http://www.jci.org/articles/view/61598?key=3b5048699eed1374fb09
ACCOMPANYING COMMENTARY
TITLE: MicroRNAs, fibrotic remodeling, and aortic aneurysms
AUTHOR CONTACT:
Dianna M. Milewicz
The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Phone: 713-500-6715; Fax: 713-500-0693; E-mail: dianna.m.milewicz@uth.tmc.edu.
View this article at:
http://www.jci.org/articles/view/62204?key=cfe9473356166fc23dff
Journal
Journal of Clinical Investigation