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Histone deacetylase inhibitors (HDACi) hold therapeutic potential for many diverse diseases, including psychiatric disease and diabetes. But so far, most HDACi were found to inhibit more than one histone deacetylase, a characteristic that can decrease efficacy and contribute to side effects. In work published in , researchers Edward Holson and Florence Wagner of the Ó³»­´«Ã½â€™s Stanley Center for Psychiatric Research, and colleagues present a toolkit of highly potent and differentially selective HDACi, which they developed to understand . The paper also reports the results of a collaboration with Bridget Wagner of Ó³»­´«Ã½â€™s Center for the Science of Therapeutics, who used the toolkit to reveal that the isoform selective inhibition of HDAC3 by BRD3308 protects pancreatic beta cells from the effects of diabetes.

Studies have shown that obese mice and humans have increased serum levels of the fatty acid binding protein aP2, and that elevated aP2 levels correlate with metabolic complications. Since genetic loss of aP2 in mouse models and in humans results in lowered risk of cardiometabolic disease, the molecule offers an exciting opportunity for new intervention strategies.

Now, in a proof-of-principle study led by Ó³»­´«Ã½ associate member Gökhan S. Hotamisligil of the Harvard T.H. Chan School of Public Health's Sabri Ãœlker Center, researchers have shown that the protein may be a viable therapeutic target for type 2 diabetes. In the study, the authors identified a monoclonal antibody to aP2 that lowered fasting blood glucose, increased insulin sensitivity, and lowered both fat mass and incidence of fatty liver in obese mouse models. Their paper is published online in .

Variation in human leukocyte antigen (HLA) genes accounts for one-half of the genetic risk in type 1 diabetes (T1D), but scientists have found it challenging to pinpoint the specific variants that account for this risk. This week, a team led by Soumya Raychaudhuri and Xinli Hu of Ó³»­´«Ã½ and Brigham and Women’s Hospital published a study that used new genotype imputation methods to identify independent amino acid positions, as well as interactions within the HLA region, that account for T1D risk. Taking this approach, they found that three key amino acid positions in HLA-DQ and HLA-DR molecules drive the vast majority of T1D risk. To learn more, online in Nature Genetics.

There are many reasons why people gain different amounts of weight and why fat becomes stored in different parts of their bodies. Now researchers conducted the largest study of genetic variation to date to home in on genetic reasons. By analyzing genetic samples from more than 300,000 individuals to study obesity and body fat distribution, researchers in the international Genetic Investigation of Anthropometric Traits (GIANT) Consortium completed the largest study of genetic variation to date, and found over 140 locations across the genome that play roles in various obesity traits.

Fat cells may be one of the most maligned cell types in the human body. For centuries, people have thought that adipose tissue – fat – was just an inert storage unit for energy. But in the last two decades, scientists have discovered that fat cells release dozens of hormones that can regulate clotting, blood pressure, appetite, insulin sensitivity, and much more. Researchers now hope to manipulate fat cells to control diseases like type 2 diabetes and obesity. But first, they need to find the pathways that govern how fat cells develop, and for that, they need a map.