The researchers found that two independent groups of cells generate the same signal by different pathways and that these cells subsequently act together to send the signal to the target cell. In this manner, the receptor cell receives the signal from two distinct sources. The results of this study appear in today ™s advanced electronic issue of the journal, PNAS.
Jordi Casanova (IRB Barcelona/CSIC) explains that different types of cells working together to send a message can be regarded as a security measure designed to ensure that the signal reaches the receptor cell in the proper fashion, neither too weakly nor too strongly. Using RNA interference techniques (RNAi), the researchers observed that it was necessary to disactivate the signal in both groups of cells in order to prevent the message from being sent. They also observed that overstimulating signal production (producing more of the signalling molecule) created problems in the receptor cell, causing it to develop incorrectly.
Researchers made the discovery by studying the behaviour of a gene called torso-like during the early stages of embryonic development of the Drosophila fly. Two groups of cells activated the same torso-like gene separately and by different mechanisms when they were still in separate compartments inside the Drosophila ovary. Subsequently, the cells migrated until they met and jointly signalled the target cell.
Marc Furriols, lead author of the study, explains that the torso-like gene activates a membrane receptor molecule that is specific to Drosophila, but that the molecule belongs to a receptor family (that includes, for example, the human growth factor), which also reacts when it receives an external signal. This research describes a very signalling mechanism in the fly which is very basic. It gives us good insight into how these mechanisms work so that we can later manipulate and control them.
Many of these pathways and signalling systems have been observed throughout evolution and hence, studies with models such as the fruit fly, can provide further insight into how these signalling mechanisms work in humans.
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These changes contributed to the ability of these mice to fend off weight gain despite a high-fat diet and lack of exercise. Together these results suggest that a CD38 deficiency has a protective effect against high-fat, diet-induced obesity, Dr. Chini says.
Dr. Chini and colleagues also examined the effects of resveratrol in mice. Resveratrol is a naturally occurring substance found in some plants such as mulberries, peanuts and red grapes used to make wine. It has been marketed as a drug that mimics the effects of moderate exercise without the physical act of exercising and also as a longevity drug, despite the lack of evidence that resveratrol is safe and effective in humans.
Mice with CD38 were treated with 30 milligrams (mg) of resveratrol per day. And, to determine the effects of the SIRT genes on obesity, mice without CD38 received the same dose of sirtinol, a drug that shuts down the SIRT genes.
Researchers found that mice with CD38 that were treated with resveratrol for two weeks were protected from high-fat, diet-induced obesity. By contrast, the protective effect against high-fat, diet-induced obesity in the absence of CD38 in mice was invalidated by sirtinol. Mice without CD38 that were treated with sirtinol gained a statistically significant amount of weight when compared with mice without the gene who were not treated with sirtinol.
This data supports the novel notion that CD38 modulates high-fat, diet-induced obesity by a SIRT- dependent mechanism.
Together these results identify a novel pathway regulating body weight and clearly show that CD38 is a nearly obligatory component of the cellular cascade that led to diet-induced obesity, the authors write.
The authors say the study's results are promising and should be explored in follow-up studies that will focus on the quality of life and longevity in mice.
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