JCI online early table of contents: Feb. 6, 2012

February 6th, 2012

EDITOR'S PICK: The heart can make 'bad' fat burn calories

Brown adipose tissue (often known as brown fat) is a specialized tissue that burns calories to generate body heat in rodents and newborn humans. Recently, adult humans have also been found to possess brown fat. This piqued the interest of researchers seeking to combat the obesity epidemic, the thought being that increasing the amount of brown fat a person has will make them lose weight. A team of researchers led by Sheila Collins, at the Sanford-Burnham Medical Research Institute, Orlando, has now determined that hormones produced by the heart known as cardiac natriuretic peptides can cause regular fat cells (white adipocytes) from mice and humans to take on characteristics of brown fat cells in vitro. Moreover, infusing one cardiac natriuretic peptide into mice caused regular white fat to upregulate markers of brown fat and increase energy usage. Collins and colleagues hope that with further mechanistic studies it might be possible to exploit these findings clinically to help combat the obesity epidemic.

In an accompanying commentary, Andrew Whittle and Antonio Vidal-Puig, at the University of Cambridge, United Kingdom, highlight the importance of the data generated by Collins and colleagues and discuss the clinical implications of the results.

TITLE: Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes

AUTHOR CONTACT:

Sheila Collins

Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.

Phone: 407-745-2134; Fax: 407-745-2032; E-mail: scollins@sanfordburnham.org.

View this article at: http://www.jci.org/articles/view/59701?key=71c8f4e7f1ce5a9bf63d

ACCOMPANYING COMMENTARY TITLE: NPs — heart hormones that regulate brown fat?

AUTHOR CONTACT:

Antonio Vidal-Puig

University of Cambridge Metabolic Research Laboratories, Institute of Metabolic

Science, Cambridge, United Kingdom.

Phone: 44-1223-762790; Fax: 44-1223-330598; E-mail: ajv22@cam.ac.uk.

View this article at: http://www.jci.org/articles/view/62595?key=c907b50be9398cbe1b30

IMMUNOLOGY: How a stomach-colonizing bacterium protects against asthma

The bacterium Helicobacter pylori can be found colonizing the stomach lining of almost half the world's population. Although persistent infection with Helicobacter pylori increases an individual's risk of developing stomach cancer, it also decreases their risk of developing asthma. A team of researchers led by Anne Müller, at the University of Zürich, Switzerland, has now identified a cellular mechanism by which persistent infection with Helicobacter pylori protects mice from developing allergic asthma. Specifically, they found that Helicobacter pylori modulated immune cells known as dendritic cells such that they did not activate an aggressive immune response but instead activated what is known as a tolerogenic immune response. Although this tolerogenic immune response enabled Helicobacter pylori to persist, it also prevented the onset of unwanted immune responses to allergens (that is, it protected against allergic asthma).

As noted by Kouji Matsushima and Shigenori Nagai, in an accompanying commentary, these data provide new mechanistic insight into the intriguing link between the recent sharp rise in the industrialized world in the number of people with asthma and the simultaneous decrease in exposure to microbes, including Helicobacter pylori.

TITLE: DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori–specific immune tolerance, and asthma protection

AUTHOR CONTACT:

Anne Müller

Institute of Molecular Cancer Research, University of Zürich, Zürich, Switzerland.

Phone 41-44-635-3474; Fax: 41-44-635-3484; E-mail: mueller@imcr.uzh.ch.

View this article at: http://www.jci.org/articles/view/61029?key=43b6bf2cd6676065e46e

ACCOMPANYING COMMENTARY TITLE: Unraveling the mystery of the hygiene hypothesis through Helicobacter pylori infection

AUTHOR CONTACT:

Kouji Matsushima

Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Phone: 81-3-5841-3431; Fax: 81-3-5841-3393; E-mail: koujim@m.u-tokyo.ac.jp.

View this article at: http://www.jci.org/articles/view/61466?key=ab4d0ae3b04251fa1b4f

ONCOLOGY: A sticky problem for stomach cancer

Gastric cancer — cancer that arises in the stomach — is a leading cause of cancer-related death. A team of researchers led by Jun Nakayama, at Shinshu University Graduate School of Medicine, Japan, has now found that gel-forming mucin secreted by glands in the stomach lining suppresses tumor-promoting inflammation in mice.

Mucin secreted by glands in the stomach lining is characterized by the presence of specific molecules at its ends. These molecules are known as alpha-1,4-linked N-acetylglucosamine residues (alpha-GlcNAc). Nakayama and colleagues found that mice lacking the ability to add alpha-GlcNAc to the ends of mucin secreted by glands in the stomach lining developed stomach cancer. Moreover, expression of alpha-GlcNAc was decreased in the majority of human gastric cancer samples examined. As their previous studies have suggested that alpha-GlcNAc–containing mucin inhibits infection with the bacterium Helicobacter pylori, which is a major risk factor for developing gastric cancer, Nakayama and colleagues suggest that alpha-GlcNAc–containing mucin prevents gastric cancer in two ways: by inhibiting Helicobacter pylori infection and by suppressing tumor-promoting inflammation.

TITLE: Essential role of gastric gland mucin in preventing gastric cancer in mice

AUTHOR CONTACT:

Jun Nakayama

Shinshu University Graduate School of Medicine, Matsumoto, Japan.

Phone: 81-263-37-3394; Fax: 81-263-37-2581; E-mail: jnaka@shinshu-u.ac.jp.

View this article at: http://www.jci.org/articles/view/59087?key=262b13135d1ff1bd59fd

ONCOLOGY: New controller of cancer cell multiplication identified

One of the hallmarks of cancer is the ability of cancer cells to proliferate in an uncontrolled manner. The proteins c-Jun and c-Myc have a key role in promoting cell proliferation, and many human cancers are characterized by aberrant expression of these proteins. Understanding how expression of c-Jun and c-Myc is controlled could provide new insight into the mechanisms underlying tumor formation as well as provide new candidate therapeutic targets. In this context, Kiyotsugu Yoshida and colleagues, at Tokyo Medical and Dental University, Japan, have determined that the protein DYRK2 has a key role in regulating levels of c-Jun and c-Myc in human cells — knocking down levels of DYRK2 in human cancer cells increased cell proliferation in vitro and upon transplantation into mice. Moreover, expression of DYRK2 was decreased in tissue samples of many different types of cancer, including breast, colon, prostate, and kidney cancers. Yoshida and colleagues therefore suggest that restoring DYRK2 expression could provide a new approach to treating many different forms of cancer.

TITLE: DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle progression in human cancer cells

AUTHOR CONTACT:

Kiyotsugu Yoshida

Tokyo Medical and Dental University, Tokyo, Japan.

Phone: 81-3-5803-5826; Fax: 81-3-5803.0242; E-mail: yos.mgen@mri.tmd.ac.jp.

View this article at: http://www.jci.org/articles/view/60818?key=3ce39f511160966595a6

ONCOLOGY: Promoting instability in cancer cells

Many cancer cells are characterized by gain or loss of whole chromosomes and/or major structural changes to chromosomes. These chromosomal changes, which are said to indicate chromosomal instability, often drive tumor formation and/or progression by causing overexpression of tumor-promoting proteins or generation of tumor-promoting fusion proteins. Understanding the mechanisms underlying chromosomal instability should provide new insight into the mechanisms underlying tumor formation/progression as well as provide new candidate therapeutic targets. In this context, a team of researchers led by Richard Pestell, at Thomas Jefferson University, Philadelphia, has now determined that the protein cyclin D1 induces chromosomal instability and increased breast tumor prevalence in mice. Moreover, analysis of human breast tumor samples indicated that cyclin D1 expression correlated with chromosomal instability in the luminal B subtype of breast cancer. Additional experiments indicated that cyclin D1 mediated its effects by increasing expression of numerous genes related to chromosomal instability. Further analysis of this mechanism could provide new targets for anticancer therapies.

TITLE: ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice

AUTHOR CONTACT:

Richard G. Pestell

Thomas Jefferson University and Hospital, Kimmel Cancer Center, Philadelphia,

Pennsylvania, USA.

Phone: 215-503-5692; Fax: 215-503-9334; E-mail: Richard.pestell@jefferson.edu.

View this article at: http://www.jci.org/articles/view/60256?key=bf3b3d5f3177c46ce3f7

NEUROLOGICAL DISEASE: Site-specific nerve damage explained

Guillain-Barré syndromes (GBSs) are medical conditions in which a person's immune system attacks their peripheral nervous system — the nerves outside the brain and spinal cord — causing varying degrees of weakness, tingling sensations, and/or pain in the legs, arms, and upper body. In individuals with the acute motor axonal neuropathy (AMAN) form of GBS, nerve damage is associated with the presence of specific immune factors: antibodies that recognize molecules known as gangliosides (anti-ganglioside antibodies [AGAbs]). A team of researchers led by Hugh Willison, at the University of Glasgow, United Kingdom, has now clarified an important open question regarding which parts of peripheral nerves are damaged by AGAbs using a variety of cell- and tissue-based model systems. These data provide new insight into ways in which nerve damage is modulated at different sites.

TITLE: Anti-ganglioside antibody internalization attenuates motor nerve terminal injury in a mouse model of acute motor axonal neuropathy

AUTHOR CONTACT:

Hugh J. Willison

Institute of Infection, Immunity and Inflammation, University of Glasgow,

Glasgow, United Kingdom.

Phone: 44-141-330-8384; Fax: 44-141-201-2993; E-mail: Hugh.Willison@glasgow.ac.uk.

View this article at: http://www.jci.org/articles/view/59110?key=c3564f6a73e1f8b5491d

Provided by Journal of Clinical Investigation