5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats.

Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus ofin uterogrowth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist

Using Light to Improve Commercial Value

The plasticity of plant morphology has evolved to maximize reproductive fitness in response to prevailing environmental conditions. Leaf architecture elaborates to maximize light harvesting, while the transition to flowering can either be accelerated or delayed to improve an individual's fitness. One of the most important environmental signals is light, with plants using light for both photosynthesis and as an environmental signal. Plants perceive different wavelengths of light using distinct photoreceptors. Recent advances in LED technology now enable light quality to be manipulated at a commercial scale, and as such opportunities now exist to take advantage of plants' developmental plasticity to enhance crop yield and quality through precise manipulation of a crops' lighting regime. This review will discuss how plants perceive and respond to light, and consider how these specific signaling pathways can be manipulated to improve crop yield and quality

Environmental effects of ozone depletion, UV radiation and interactions with climate change : UNEP Environmental Effects Assessment Panel, update 2017

Peer reviewe

Activity of dietary fatty acids on FFA1 and FFA4 and characterisation of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases

Various foods are associated with effects against metabolic diseases such as insulin resistance and type 2 diabetes; however, their mechanisms of action are mostly unclear. Fatty acids may contribute by acting as precursors of signalling molecules or by direct activity on receptors. The medium- and long-chain NEFA receptor FFA1 (free fatty acid receptor 1, previously known as GPR40) has been linked to enhancement of glucose-stimulated insulin secretion, whereas FFA4 (free fatty acid receptor 4, previously known as GPR120) has been associated with insulin-sensitising and anti-inflammatory effects, and both receptors are reported to protect pancreatic islets and promote secretion of appetite and glucose-regulating hormones. Hypothesising that FFA1 and FFA4 mediate therapeutic effects of dietary components, we screened a broad selection of NEFA on FFA1 and FFA4 and characterised active compounds in concentration–response curves. Of the screened compounds, pinolenic acid, a constituent of pine nut oil, was identified as a relatively potent and efficacious dual FFA1/FFA4 agonist, and its suitability for further studies was confirmed by additional in vitro characterisation. Pine nut oil and free and esterified pure pinolenic acid were tested in an acute glucose tolerance test in mice. Pine nut oil showed a moderately but significantly improved glucose tolerance compared with maize oil. Pure pinolenic acid or ethyl ester gave robust and highly significant improvements of glucose tolerance. In conclusion, the present results indicate that pinolenic acid is a comparatively potent and efficacious dual FFA1/FFA4 agonist that exerts antidiabetic effects in an acute mouse model. The compound thus deserves attention as a potential active dietary ingredient to prevent or counteract metabolic diseases

Discovery of a potent free fatty acid 1 receptor agonist with low lipophilicity, low polar surface area and robust in vivo efficacy

The free fatty acid receptor 1 (FFA1 or GPR40) is established as an interesting potential target for treatment of type 2 diabetes. However, to obtain optimal ligands, it may be necessary to limit both lipophilicity and polar surface area, translating to a need for small compounds. We here describe the identification of 24, a potent FFA1 agonist with low lipophilicity and very high ligand efficiency that exhibit robust glucose lowering effect

The UV-B photoreceptor UVR8 promotes photosynthetic efficiency in Arabidopsis thaliana exposed to elevated levels of UV-B

The UV-B photoreceptor UVR8 regulates expression of genes in response to UV-B, some encoding chloroplast proteins, but the importance of UVR8 in maintaining photosynthetic competence is unknown. The maximum quantum yield of PSII (F v/F m) and the operating efficiency of PSII (Φ PSII) were measured in wild-type and uvr8 mutant Arabidopsis thaliana. The importance of specific UVR8-regulated genes in maintaining photosynthetic competence was examined using mutants. Both F v/F m and Φ PSII decreased when plants were exposed to elevated UV-B, in general more so in uvr8 mutant plants than wild-type. UV-B increased the level of psbD-BLRP (blue light responsive promoter) transcripts, encoding the PSII D2 protein. This increase was mediated by the UVR8-regulated chloroplast RNA polymerase sigma factor SIG5, but SIG5 was not required to maintain photosynthetic efficiency at elevated UV-B. Levels of the D1 protein of PSII decreased markedly when plants were exposed to elevated UV-B, but there was no significant difference between wild-type and uvr8 under conditions where the mutant showed increased photoinhibition. The results show that UVR8 promotes photosynthetic efficiency at elevated levels of UV-B. Loss of the DI polypeptide is probably important in causing photoinhibition, but does not entirely explain the reduced photosynthetic efficiency of the uvr8 mutant compared to wild-type