Editorial: Women in integrative physiology: 2021

Ye

Assessing the prevalence and potential drivers of food insecurity and the relationship with mental wellbeing in UK university students: A cross-sectional study

Food insecurity (FI) among university students in the United States has been associated with poor mental wellbeing, but very little is known about the rela-tionship between FI and mental wellbeing in the UK university population. Here we examined the prevalence of FI, determined potential drivers for it and its relationship with mental wellbeing and coping ability. Students studying at UK universities (n= 289) completed an online self-reported questionnaire to obtain socio-economic characteristics including financial status, FI status (Household Food Insecurity Access scale), mental wellbeing (Warwick-Edinburgh Mental Wellbeing Scale) and coping ability (coping flexibility scale). FI was observed in 28% of the participants and was associated with financial independence, run-ning out of money, borrowing money and lacking confidence to purchase healthy foods (p< 0.05). Although we cannot determine directionality, logistic regression analysis revealed those who were judged as FI were more likely to shop often (OR= 3.139 95% CI 1.533–6.429), never snacked between meals (OR = 4.261 95% CI 1.309–13.875) and the amount of food purchased was affected by perceptions of the price of food in general (OR = 2.954 95% CI 1.675–5.210). Financial instability and the inability to access nutritious food may contribute to the decrease in mental wellbeing (p< 0.01) and lower ability to cope with stress-ful situations (p< 0.01) in food-insecure students although the direction of these relationships cannot be determined from this cross-sectional study. This study has identified that there is a need to develop appropriate strategies to combat FI in university students and to improve mental health

Could consumption of yam (Dioscorea) or its extract be beneficial in controlling glycaemia - a systematic review

Yam (Dioscorea spp.) and its associated extracts have been shown to possess a variety of biological activities and identified as beneficial in the control of glycaemia in patients with Type II Diabetes Mellitus (T2DM). The objective was to conduct a systematic search of the literature to investigate whether yam and its extract can improve glycaemia and whether consumption of yam could be beneficial for managing T2DM. Using the PRISMA guidelines and the PICO framework, three databases (PubMed, Scopus, and Web of Science) were searched using a key term strategy. Strict inclusion criteria were employed to identify all relevant and available studies. The quality of these studies was assessed using SYRCLE's Risk of Bias tool. Ten studies were included; and all studies consisted of findings from rodent models of diabetes, including animals consuming high fat diets or genetic models of diabetes. All ten studies showed that consumption of yam and/or its extract (containing dioscin, dioscorin, diosgenin, DA-9801/02, or Chinese yam polysaccharides) improved glycaemia. These included improvements in fasting blood glucose and reductions in glucose and increase in insulin levels following a glucose tolerance test. Furthermore, significant changes in body weight and adiposity were observed in nine studies, these included improvements in lipid biomarkers in four and reductions in inflammatory markers in one. The current work indicates that the consumption of yam or its extracts can be beneficial for improving blood glucose however the molecular mechanism for these effects remain largely unknown. Future trials on human subjects are warranted

Neuroendocrine role for VGF

The vgf gene (non-acronymic) is highly conserved and was identified on the basis of its rapid induction in vitro by nerve growth factor, although can also be induced by brain derived neurotrophic factor, and glial derived growth factor. The VGF gene gives rise to a 68kDa precursor polypeptide which is induced robustly, relatively selectively and is synthesized exclusively in neuronal and neuroendocrine cells. Post-translational processing by neuroendocrine specific pro-hormone convertases in these cells results in the production of a number of smaller peptides. The VGF gene and peptides are widely expressed throughout the brain, particularly the hypothalamus and hippocampus, and in peripheral tissues including the pituitary gland, the adrenal glands and the pancreas, and in the gastrointestinal tract in both the myenteric plexus and in endocrine cells. VGF peptides have been associated with a number of neuroendocrine roles and in this mini-review we aim to describe these roles to highlight the importance of VGF as therapeutic target for a number of disorders, particularly those associated with energy metabolism, pain, reproduction and cognition

Active vitamin D increases myogenic differentiation in C2C12 cells via a vitamin D response element on the myogenin promoter

Background Skeletal muscle development during embryogenesis depends on proliferation of myoblasts followed by differentiation into myotubes/ multinucleated myofibers. Vitamin D (VD) has been shown to affect these processes, but there is conflicting evidence within the current literature on the exact nature of these effects due to a lack of time course data. With 20-40% of pregnant women worldwide being VD deficient, it is crucial that a clearer understanding of the impact of VD on myogenesis is gained.Methods A detailed 8-day differentiation time course was used where C2C12 cells were differentiated in control media (2% horse serum or 0.1% ethanol) or with different concentrations of active VD, 1,25(OH)2D3 (10-13M, 10-11M, 10-9M or 10-7M), and measurements were taken at 6 time points. DNA, creatine kinase and protein assays were carried out as well as quantitative PCR to determine expression of Myf5, MyoD, myogenin, MHC I, MHC neonatal, MHC embryonic, MHC IIa, MHC IIx and MHC IIb mRNAs. Transfections were carried out using one vector containing the myogenin promoter and another containing the same promoter with a 3 base mutation within a putative vitamin D response element (VDRE) to determine effects of 1,25(OH)2D3 on myogenin transcription. Finally, a ChIP assay was performed to determine whether the VD receptor (VDR) binds to the putative VDRE.Results 1,25(OH)2D3 caused an inhibition of proliferation and an increase in differentiation in C2C12 cells. Myf5, myogenin, MHC I, MHC neonatal, MHC embryonic, MHC IIa, MHC IIx and MHC IIb expression were all increased by 1,25(OH)2D3. Myotube size was also increased by VD. When the putative VDRE on the myogenin promoter was mutated, the increase in expression by VD was lost. ChIP analysis revealed that the VDR does bind to the putative VDRE on the myogenin promoter.Conclusions Active VD directly increases myogenin transcription via a functional VDRE on the myogenin promoter, resulting in increased myogenic differentiation, increased expression of both the early and late MHC isoforms, and also increased myotube size. These results highlight the importance of VD status during pregnancy for normal myogenesis to occur, but further in vivo work is needed

Thyroid hormone and vitamin D regulate VGF expression and promoter activity

The Siberian hamster (Phodopus sungorus) survives winter by decreasing food intake and catabolizing abdominal fat reserves, resulting in a sustained, profound loss of body weight. Hypothalamic tanycytes are pivotal for this process. In these cells, short-winter photoperiods upregulate deiodinase 3, an enzyme that regulates thyroid hormone availability, and downregulate genes encoding components of retinoic acid (RA) uptake and signaling. The aim of the current studies was to identify mechanisms by which seasonal changes in thyroid hormone and RA signaling from tanycytes might ultimately regulate appetite and energy expenditure. proVGF is one of the most abundant peptides in the mammalian brain, and studies have suggested a role for VGF-derived peptides in the photoperiodic regulation of body weight in the Siberian hamster. In silico studies identified possible thyroid and vitamin D response elements in the VGF promoter. Using the human neuroblastoma SH-SY5Y cell line, we demonstrate that RA increases endogenous VG expression (P!0.05) and VGF promoter activity (P!0.0001). Similarly, treatment with 1,25-ihydroxyvitamin D3 increased endogenous VGF mRNA expression (P!0.05) and VGF promoter activity (P!0.0001),whereas triiodothyronine (T3) decreased both (P!0.01 and P!0.0001). Finally, intrahypothalamic administration of T3 blocked the short day-induced increase in VGF expression in the dorsomedial posterior arcuate nucleus of Siberian hamsters. Thus, we conclude that VGF expression is a likely target of photoperiod-induced changes in tanycyte-derived signals and is potentially a regulator of seasonal changes in appetite and energy expenditure

Neuromedin U receptors in GtoPdb v.2023.1

Neuromedin U receptors (provisional nomenclature as recommended by NC-IUPHAR [30]) are activated by the endogenous 25 amino acid peptide neuromedin U (neuromedin U-25, NmU-25), a peptide originally isolated from pig spinal cord [92]. In humans, NmU-25 appears to be the sole product of a precursor gene (NMU, P48645) showing a broad tissue distribution, but which is expressed at highest levels in the upper gastrointestinal tract, CNS, bone marrow and fetal liver. Much shorter versions of NmU are found in some species, but not in human, and are derived at least in some instances from the proteolytic cleavage of the longer NmU. Despite species differences in NmU structure, the C-terminal region (particularly the C-terminal pentapeptide) is highly conserved and contains biological activity. Neuromedin S (neuromedin S-33) has also been identified as an endogenous agonist [97]. NmS-33 is, as its name suggests, a 33 amino-acid product of a precursor protein derived from a single gene and contains an amidated C-terminal heptapeptide identical to NmU. NmS-33 appears to activate NMU receptors with equivalent potency to NmU-25

Neuromedin U receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Neuromedin U receptors (provisional nomenclature as recommended by NC-IUPHAR [29]) are activated by the endogenous 25 amino acid peptide neuromedin U (neuromedin U-25, NmU-25), a peptide originally isolated from pig spinal cord [90]. In humans, NmU-25 appears to be the sole product of a precursor gene (NMU, P48645) showing a broad tissue distribution, but which is expressed at highest levels in the upper gastrointestinal tract, CNS, bone marrow and fetal liver. Much shorter versions of NmU are found in some species, but not in human, and are derived at least in some instances from the proteolytic cleavage of the longer NmU. Despite species differences in NmU structure, the C-terminal region (particularly the C-terminal pentapeptide) is highly conserved and contains biological activity. Neuromedin S (neuromedin S-33) has also been identified as an endogenous agonist [95]. NmS-33 is, as its name suggests, a 33 amino-acid product of a precursor protein derived from a single gene and contains an amidated C-terminal heptapeptide identical to NmU. NmS-33 appears to activate NMU receptors with equivalent potency to NmU-25

In vitro Effects of Biologically Active Vitamin D on Myogenesis: A Systematic Review

Vitamin D (VD) deficiency is associated with muscle weakness. A reduction in the incidence of falls in the elderly following VD supplementation and identification of the VD receptor within muscle cells suggests a direct effect of VD on muscle, but little is known about the underlying mechanisms. Here we systematically searched the literature to identify effects of active VD [1,25(OH)2D3] on skeletal muscle myogenesis in vitro, with no restriction on year of publication. Eligibility was assessed by strict inclusion/exclusion criteria and agreed by two independent investigators. Twelve relevant pa-pers were identified using four different cell types (C2C12, primary mouse satellite cells, primary chick myoblasts, and primary human myoblasts) and a range of myogenic markers (myoD, myogenin, creatine kinase, myosin heavy chain, and myotube size). A clear inhibitory effect of 1,25(OH)2D3 on proliferation was reported, while the effects on the different stages of differentiation were less consistent probably due to variation in cell type, time points and doses of 1,25(OH)2D3 used. However, myotube size was consistently increased by 1,25(OH)2D3. Overall, the evidence suggests that 1,25(OH)2D3 inhibits proliferation and promotes differentiation of myoblasts, but future studies should use time courses to gain a clearer understanding

VGF-peptides in the Siberian hamster

vgf is one of the few genes selectively induced in the hypothalamus of Siberian hamsters upon their typical change from an obese phenotype (long day adaptation, during summer) to a lean, catabolic phenotype (short day, or winter adaptation). In fact, the i.c.v. injection of the VGF-derived peptide TLQP-21 caused hypophagia and a decrease in body weight in long day hamster. Hence, we studied VGF multi-peptide profiles in brain cortex and hypothalamus of (male) Siberian hamsters, in the long day (LD) versus short day (SD) adapted state. Specific antisera were produced against short sequences at the C- or N-termini of VGF, and of several known/predicted VGF-derived products: TLQP, NERP-1, and PGH peptides, and used in immunohistochemistry (IHC) and ELISA. Hamsters were perfused with 4% paraformaldehyde (n= 4/group) for IHC or used for tissue sampling and extraction (n= 7/group). In IHC, VGF C- and N- terminus peptides were brightly labelled, as well as most abundant. They were found in both perikarya and axons, in different layers of brain cortex and in multiple hypothalamic areas, including the paraventricular (PVN), suprachiasmatic (SCN), supraoptic (SON) and arcuate nuclei, the lateral and anterior hypothalamic areas, and the median eminence (ME). TLQP peptides were largely restricted to SCN perikarya, and ME axons, while PGH and NERP-1 peptides were revealed in perikarya of the brain cortex, in ME axons, and certain perikarya of PVN and SON (NERP-1 only). Most VGF peptides studied were well represented in tissue extracts of hypothalamus and cortex, VGF C- and N- terminus peptides being again most abundant (hypothalamus: 1.8±0.3 and 10.9±0.6; cortex: 0.7±0.1 and 5±0.3 nmol/g, mean±SEM, C- and N-terminus, respectively, LD animals). A selective decrease in certain VGF peptides was revealed in SD animals, compared to LD ones, so that NERP-1 peptides were decreased in hypothalamus and cortex (61.3±12.7% and 45.8±11.1% of LD animals, respectively, mean±SEM, p&lt;0.04), PGH peptides were reduced in hypothalamus (24.8±12.7% of LD group, mean±SEM, p&lt;0.02), and both TLQP and N-terminus peptides in the brain cortex (31.8±10.9% and 41.5±10.8% of LD animals, respectively, mean±SEM, p&lt;0.02). In conclusion, VGF peptides were well represented in the Siberian hamster brain, with a distinct, apparently selective modulation in the hypothalamus and brain cortex. A regionally specific, differential post-translational processing of the VGF precursor may be implicated. Supported by a RAS grant (Regione Autonoma Sardegna, PO FSE 2007-1013, L.R. 7/2007)