It’s well-known that the offspring of obese parents tend to become obese themselves. Both environmental and genetic factors govern this association. Recently, a pair of studies has shed considerable light on those genetic factors, and in particular the role that a father’s diet has on his kids.

In the first study, Sheau-Fang Ng and colleagues at the University of New South Wales randomized a cohort of male rats to receive either a high-calorie diet or a healthy diet, and then had them mate with normal, healthy female rats.

The scientists found that as the daughters of the obese dads grew to become adults, they exhibited impaired glucose tolerance and elevated insulin levels that were not seen in the daughters of normal-weight dads. This turned out to be true even though both sets of offspring had similar amounts of fat and muscle mass, and similar blood triglyceride and leptin levels.

The scientists performed genetic studies on the 2 groups to better understand the cause of these differences. These studies revealed that 642 genes were expressed differently in the 2 groups, and all of them were involved with glucose metabolism and insulin production. The anatomic site where the changes had their impact was localized to pancreatic B-cells which are known to produce insulin.

In their write-up, Sheau-Fang’s group claimed that theirs was “the first direct demonstration in any species that a paternal environmental exposure can induce intergenerational transmission of impaired glucose-insulin homeostasis in their female offspring.” (more…)

Scientists from Columbia University are reporting that osteoporosis, a chronic bone-wasting condition that affects 10 million elderly Americans, may be mediated by serotonin, a compound previously known for its role in brain functioning.

The astonishing conclusion appears in the journal Cell.

Scientists had known for years that a rare, inherited brittle bone disease was caused by a mutation of a gene known as LRP5. More recently, a second mutation of LRP5 was reported to cause just the opposite—bones so dense that tooth extractions became nearly impossible.

So something was up with LRP5, and the tempting assumption was that the gene directly impacted bone formation.

Not so, according to Gerard Karsenty and colleagues. They proved that LRP5 blocks production of serotonin in the gut.

Then they proved that while gut serotonin has no impact on brain functioning, it does impair bone formation after travelling there through the blood stream.

“We made mice with the inactivated gene,” Dr. Karsenty told the New York Times. These mice had 4 times the normal levels of circulating gut serotonin, and in their bodies “the bone-forming cells are on strike,” he added.

The mice developed marked osteoporosis.

Karsenty’s team then harvested bone cells from the brittle boned mice and proved in the laboratory that the cells were perfectly capable of normal development and functioning, so long as they were not bathed in serotonin.

Karsenty’s team hopes its work might prompt development of a drug that suppresses gut serotonin synthesis and thus stimulate bone growth in osteoporosis patients.

Scientists know that resveratrol, a compound found in red wine improves health and longevity in laboratory mice. Now they’re beginning to figure out how.

David Sinclair and colleagues at Harvard have concluded that resveratrol activates sirtuin, a protein normally involved in gene expression and chromosomal repair.

Sinclair’s group had previously developed compounds that mimic the effects of resveratrol. One such compound was recently found to help mice stay thin despite consuming a high calorie, high fat diet, presumably by regulating gene expression.

Using these same compounds, Sinclair’s group has now demonstrated that sirtuin improves longevity in certain mouse cell cultures by suppressing transcription of proteins associated with aging. The group speculated in Cell last week that sirtuin may govern similar processes in intact mice (not just their cell cultures) and perhaps humans.

This research helps flesh out an exciting story about sirtuin. It looks like the protein performs 2 major functions. First, it assures that cells can access only the few genes they actually need to carry out their duties. This involves preventing access to 20,000 other genes that are in the DNA of every cell.

Sirtuin governs access to genes by wrapping around non-essential DNA, creating a protective shield.

Second, sirtuin repairs DNA when it breaks or gets damaged, as happens during normal aging or following radiation exposure, say from sunlight.

The problem is that when sirtuin gets involved in DNA repair, it loses effectiveness as a gene access manager. This leads to abnormal gene expression which somehow contributes to cell aging and cell death.

In a nutshell, we know that cell differentiation, aging and death are mediated by a common biochemical pathway in which sirtuin is a player, and we have compounds that activate sirtuin. This could get interesting.