More News From The Journal Of Clinical Investigation: April 1, 2010
One thing that predisposes individuals who are obese to type 2 diabetes is the persistent, low-level inflammation that results, in part, from dysregulation of the function of white fat tissue in the abdominal cavity between the internal organs (visceral white fat tissue). New insight into the signaling pathways that contribute to visceral white fat tissue dysregulation has now been provided by Philippe Lefebvre and colleagues, at INSERM, UMR1011, France, who determined that the PPAR-gamma signaling pathway operates differently in the visceral white fat tissue of lean and obese mice and humans. Specifically, it shows increased sensitivity to activation by the anti-diabetic drug rosiglitazone in obese mice and humans. These data therefore provide a mechanistic explanation why rosiglitazone acts differently in lean and obese patients.
TITLE: Proteasomal degradation of retinoid X receptor-alpha reprograms transcriptional activity of PPAR-gamma in obese mice and humans
GASTROENTEROLOGY: Enteroendocrine cells in the gut needed for optimal postnatal survival
Enteroendocrine cells are cells found in the wall of the gut that secrete hormones that regulate numerous processes in the body, including controlling glucose levels, food intake, and stomach emptying. There are at least ten types of enteroendocrine cell and it has been hard to determine the exact role of each cell type and hormone they secrete because many of the hormones have partially overlapping functions. However, a team of researchers, led by Georg Mellitzer and Gérard Gradwohl, at INSERM U964, Université de Strasbourg, France, has now generated mice lacking all enteroendocrine cells and hormones by deleting the gene Ngn3 and found that a lack of these cells leads to a high chance of dying during the first week of life. Surviving mice were smaller than normal littermates, had soft stool, and were impaired in their ability to absorb fat in the intestines. The clinical relevance of these data are highlighted by the recent identification of several patients with NGN3 gene mutations who show an almost complete lack of all enteroendocrine cells and suffer, from the first days of life, from malabsorptive chronic diarrhea.
TITLE: Loss of enteroendocrine cells in mice alters lipid absorption and glucose homeostasis and impairs postnatal survival
LYMPHATIC SYSTEM: Regulator of lymph vessel growth uncovered
In addition to our network of blood vessels, humans have a network of vessels known as lymphatic vessels. These vessels have a role in many processes in the body, including regulating fluid levels in tissues and immune surveillance. Although dysfunction in the lymphatic system contributes to human diseases such as the spread of cancer to other sites and lymphademas (localized fluid retention and tissue swelling), little is known about the molecules that regulate the formation of new lymphatic vessels, a process known as lymphangiogenesis. However, a team of researchers, led by Sophia Tsai and Ming-Jer Tsai, at Baylor College of Medicine, Houston, has now identified a role for the gene regulatory protein COUP-TFII in lymphangiogenesis in mouse embryonic development and tumor lymphangiogenesis in adult mice. The authors therefore suggest that COUP-TFII might be an effective molecular target in pro-lymphangiogenic treatment of lymphedemas or in antilymphangiogenic therapy targeting tumor spreading via the lymphatic vessels.
TITLE: Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development
Journal of Clinical Investigation