Biological examination of melanin concentrating hormone receptor 1: multi-tasking from the hypothalamus.

Since its discovery as the first receptor for the orexigenic neuropeptide melanin-concentrating hormone (MCH), the MCH receptor, MCHR1, has been actively pursued for therapeutic intervention in the treatment of obesity. Mice with targeted deletion of MCHR1 or its cognate ligand, MCH, generally have decreased body weight and fat mass and are resistant to diet-induced obesity compared with their wild-type counterparts. Mice treated via intracerebroventricular infusion with MCH, or that overexpress MCH or MCHR1, exhibit weight gain compared with control animals. MCHR1 is also a central target of leptin signaling and appears to be a mediator of insulin resistance. The distribution of MCH and MCHR1 in rat brain, outside of regions that control appetite and satiety, has led to the finding that MCH signaling participates in other functions such as emotion and stress. This review will describe in detail the biological studies that show how MCH and MCHR1 control numerous physiological functions. The current status of the development of MCHR1 antagonists for clinical use will also be assessed. Given the substantial link between obesity and its many associated afflictions, a single pharmaceutical agent that could be used to treat multiple pathologies would be welcome.

Genetic control of storage oil synthesis in seeds of Arabidopsis.

Quantitative trait loci (QTL) that control seed oil content and fatty acid composition were studied using a recombinant inbred population derived from a cross between the Arabidopsis ecotypes Landsberg erecta and Cape Verdi Islands. Multiple QTL model mapping identified two major and two minor QTL that account for 43% of the variation in oil content in the population. The most significant QTL is at the bottom of chromosome 2 and accounts for 17% of the genetic variation. Two other significant QTL, located on the upper and lower arms of chromosome 1, account for a further 19% of the genetic variation. A QTL near to the top of chomosome 3 is epistatic to that on the upper arm of chromosome 1. There are strong QTL for linoleic (18:2) and linolenic (18:3) acids contents that colocate with the FAD3 locus, another for oleic acid (18:1) that colocates with FAD2 and other less significant QTL for palmitic (16:0), stearic (18:0), and eicosaenoic (20:1) acids. The presence of the QTL for seed oil content on chromosome 2 was confirmed by the generation of lines that contain a 22-cM region of Landsberg erecta DNA at the bottom of chromosome 2 in a background containing Cape Verdi Islands in other regions of the genome that had been shown to influence oil content in the QTL analysis.

Natural variation for seed oil composition in Arabidopsis thaliana.

The biochemical pathways involved in the biosynthesis and accumulation of storage lipids in seeds have been extensively studied. However, the regulatory mechanisms of those pathways, their environmental interactions and the ecological implications of variation are poorly understood. We have initiated a new approach: the analysis of natural variation in Arabidopsis thaliana. Three hundred and sixty accessions were surveyed for content of oil, very long chain fatty acids (VLCFAs) and polyunsaturated fatty acids (PUFAs) in their seeds. The results revealed extensive natural variation. A core set of accessions, the seeds of which reproducibly contain extreme amounts of oil, VLCFAs and PUFAs have been identified. Reproducible oil content ranged from 34.6 to 46.0% of seed dry weight. VLCFA content ranged from 13.0 to 21.2% of total fatty acids. PUFA content, ranged from 53.3 to 66.1% of total fatty acids. Interactions were also identified for PUFA and VLCFA content of seeds with vernalisation of plants. Mapping of the regions of the genome involved in controlling the traits was conducted in an F(2) population and indicated that natural variation at the loci FAE1 and FAD3 might be involved in the regulation of VLCFA and PUFA content, respectively. A set of accessions, which capture a broad range of the natural variation for these traits available in A. thaliana, has been selected to form a core set which can be used to further dissect the genetics of the regulation of seed lipid traits and to identify the genes involved.