Body mass and fat intake are multifactorial traits that have genetic and environmental components. The gene with the greatest effect on body mass is FTO (fat mass and obesity-associated), but several studies have shown that the effect of FTO (and of other genes) on body mass can be modified by the intake of nutrients. The so-called gene–environment interactions may also be important for the effectiveness of weight-loss strategies. Food choices, and thus fat intake, depend to some extent on individual preferences. The most important biological component of food preference is taste, and the role of fat sensitivity in fat intake has recently been pointed out. Relatively few studies have analysed the genetic components of fat intake or fatty acid sensitivity in terms of their relation to obesity. It has been proposed that decreased oral fatty acid sensitivity leads to increased fat intake and thus increased body mass. One of the genes that affect fatty acid sensitivity is CD36 (cluster of differentiation 36). However, little is known so far about the genetic component of fat sensing. We performed a literature review to identify the state of knowledge regarding the genetics of fat intake and its relation to body-mass determination, and to identify the priorities for further investigations.

Elucidating the detailed process of ligand binding to a receptor is pharmaceutically important for identifying druggable binding sites. With the ability to provide atomistic detail, computational methods are well poised to study these processes. Here, accelerated molecular dynamics (aMD) is proposed to simulate processes of ligand binding to a G-protein-coupled receptor (GPCR), in this case the M3 muscarinic receptor, which is a target for treating many human diseases, including cancer, diabetes and obesity. Long-timescale aMD simulations were performed to observe the binding of three chemically diverse ligand molecules: antagonist tiotropium (TTP), partial agonist arecoline (ARc) and full agonist acetylcholine (ACh). In comparison with earlier microsecond-timescale conventional MD simulations, aMD greatly accelerated the binding of ACh to the receptor orthosteric ligand-binding site and the binding of TTP to an extracellular vestibule. Further aMD simulations also captured binding of ARc to the receptor orthosteric site. Additionally, all three ligands were observed to bind in the extracellular vestibule during their binding pathways, suggesting that it is a metastable binding site. This study demonstrates the applicability of aMD to protein–ligand binding, especially the drug recognition of GPCRs.

Accumulating evidence indicates that, analogous to n-6 PUFA, n-3 PUFA are enzymatically converted into diverse families of bioactive mediators that play numerous roles in physiology. These mediators, which include the resolvins, protectins and maresins, are particularly important in resolving acute inflammation and also appear to play a role in enhancing host defence. Given the protective actions of n-3 PUFA in human subjects and in animal models of disease, active generation of bioactive mediators may in part underlie these protective effects. Several studies have demonstrated that bioactive autacoids generated from n-3 PUFA have direct anti-inflammatory and pro-resolution actions, and the structures of many of these endogenous mediators have been elucidated. The diverse roles of these lipid mediators in health and disease, regulation of their biosynthesis, as well as identification of specific receptors and cellular targets, are emerging. This brief review will highlight the biosynthesis of resolvins, protectins and maresins, and discuss their receptor-mediated biological actions in promoting the resolution of inflammation. Their potential use as a new class of pro-resolution therapeutics, as well as gaps in knowledge and challenges for future research, will also be discussed. Overall, the identification of these novel families of lipid mediators has yielded insight into the protective actions of n-3 PUFA and may lead to the development of an entirely new class of therapeutics aimed at regulating inflammation and host defence.

Astrocytes constitute a major group of glial cells which were long regarded as passive elements, fulfilling nutritive and structural functions for neurons. Calcium rise in astrocytes propagating to neurons was the first demonstration of direct interaction between the two cell types. Since then, calcium has been widely used, not only as an indicator of astrocytic activity but also as a stimulator switch to control astrocyte physiology. As a result, astrocytes have been elevated from auxiliaries to neurons, to cells involved in processing synaptic information. Curiously, while there is evidence that astrocytes play an important role in synaptic plasticity, the data relating to calcium's pivotal role are inconsistent. In this review, we will detail the various mechanisms of calcium flux in astrocytes, then briefly present the calcium-dependent mechanisms of gliotransmitter release. Finally, we will discuss the role of calcium in plasticity and present alternative explanations that could reconcile the conflicting results published recently.