The unhealthy diet has deleterious consequences even after the fats were removed from the diet and has links to insulin production.

We know that foetal growth is influenced by the mother's nutritional status, explained Brazilian nutritionist Luciana Pisani. The nutritional conditions during pregnancy has a major role in the metabolic and hormonal interactions between the mother's body, placenta and foetus. To date only a few studies have looked at the effects on trans fatty acids during pregnancy and lactation on the metabolism of offspring in adulthood. We found that the fatty content of the babies' bodies increased when the mothers were fed the hydrogenated fat rich diet and this could be traced to the gene expression of adipokines.

In an investigation to examine whether feeding pregnant and lactating rats hydrogenised fats rich in trans fatty acids, increased the fat content in carcass, the researchers found that their metabolic rate dropped dramatically. Interestingly young rats that were fed a normal diet after they were born ate less and weighed less even though their mothers had been eating the trans fatty acids while pregnant. The gene expression of adipokines was also examined in relation to insulin production.

The offspring were weighed weekly and exposure to the trans-fatty acid enriched diet after weaning led to a 40% increase in body fat content for the young rats. Rats whose mothers were fed the trans fatty acids and continued to eat the fats into adulthood had the highest metabolic efficiency. The same rats increased their insulin production.

Pisani continued, Fats play a fundamental role in foetal development and changes in dietary fatty acids has important implications for foetal and postnatal development. Heavy ingestion of very hydrogenated fats rich in trans fatty acids increases risk of cardiovascular diseases and reduces insulin sensitivity and so leads to type 2 diabetes. We need to investigate this further as this has important implications for people's own diets, especially pregnant women.

biomedcentral/

One MHC variation linked to psoriasis and psoriatic arthritis occurs in the gene HCP5, the scientists noted. That variation was recently reported to delay the onset of AIDS in people infected with HIV. This is particularly interesting, Bowcock says, because psoriasis can be triggered by infection with HIV or other viruses. It may be that in people with this SNP variant, viral infection triggers a larger immune response that slows the development of AIDS but also leads to excessive inflammation in the skin and bone joints in genetically susceptible individuals, leading to the onset of psoriasis and psoriatic arthritis.

Notably, DNA variations on chromosome 4 were strongly linked to psoriatic arthritis. These same variations were also associated with psoriasis and had been previously linked to type 1 diabetes, rheumatoid arthritis, Grave's disease (caused by an overproductive thyroid gland) and celiac disease (caused by the inability to digest gluten). "Doctors have noticed that some psoriasis patients have autoimmune diseases such as celiac disease, Grave's disease, and type 1 diabetes," Bowcock says. "But we didn't know whether this was a coincidence. Now we know there is a genetic component underlying all of these diseases."

The same region of chromosome 4 contains genes that code for the signaling molecules IL2 and IL21. This opens the door to investigating whether existing drugs that block either molecule may be effective in some psoriasis patients, especially those with psoriatic arthritis.

The researchers also uncovered significant DNA variations on chromosome 13 in a genetic region involved in modifying proteins, and on chromosome 15, in a region responsible for producing a protein that activates TNF alpha (tumor necrosis factor-alpha) in a specialized immune cell known as a dendritic cell. While TNF alpha normally helps fight infections, it is thought to be a major player in psoriasis and psoriatic arthritis. Several FDA-approved psoriasis medications work by binding to TNF-alpha, thereby preventing it from communicating with cells.

Bowcock is now involved in a larger genome-wide association study of psoriasis patients and says she expects it will uncover additional genetic variations that are associated with psoriasis.

Eventually, she predicts, such studies will lead to more effective, better-targeted therapies.

"The goal of this study and other genome-association studies is to get to personalized medicine, where you can diagnose a disease and ask what genetic risk factors this person has that points to altered pathways," she says. "Then, we can target those pathways for specific therapeutic interventions."

medicine.wustl/