Effects of acute exercise and exercise training on plasma GDF15 concentrations and associations with appetite and cardiometabolic health in individuals with overweight or obesity – A secondary analysis of a randomized controlled trial

Growth Differentiation Factor 15 (GDF15) is seemingly involved in appetite control. Acute exercise increases GDF15 concentrations in lean humans, but acute and long-term effects of exercise on GDF15 in individuals with overweight/obesity are unknown. We investigated the effects of acute exercise and exercise training on GDF15 concentrations in individuals with overweight/obesity and associations with appetite and cardiometabolic markers. 90 physically inactive adults (20–45 years) with overweight/obesity were randomized to 6-months habitual lifestyle (CON, n=16), or isocaloric exercise of moderate (MOD, n=37) or vigorous intensity (VIG, n=37), 5 days/week. Testing was performed at baseline, 3, and 6 months. Plasma GDF15 concentrations, other metabolic markers, and subjective appetite were assessed fasted and in response to acute exercise before an ad libitum meal. Cardiorespiratory fitness, body composition, insulin sensitivity, and intraabdominal adipose tissue were measured. At baseline, GDF15 increased 18% (95%CI: 4; 34) immediately after acute exercise and 32% (16; 50) 60 min post-exercise. Fasting GDF15 increased 21% (0; 46) in VIG after 3 months (p=0.045), but this attenuated at 6 months (13% (−11; 43), p=0.316) and was unchanged in MOD (11% (−6; 32), p=0.224, across 3 and 6 months). Post-exercise GDF15 did not change in MOD or VIG. GDF15 was not associated with appetite or energy intake. Higher GDF15 was associated with lower cardiorespiratory fitness, central obesity, dyslipidemia, and poorer glycemic control. In conclusion, GDF15 increased in response to acute exercise but was unaffected by exercise training. Higher GDF15 concentrations were associated with a less favorable cardiometabolic profile but not with markers of appetite. This suggests that GDF15 increases in response to acute exercise independent of training state. Whether this has an impact on free-living energy intake and body weight management needs investigation

Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration

Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood. Here we addressed the influence of VZV on leukocyte migration and found that the purified recombinant soluble ectodomain of VZV glycoprotein C (rSgC) binds chemokines with high affinity. Functional experiments show that VZV rSgC potentiates chemokine activity, enhancing the migration of monocyte and T cell lines and, most importantly, human tonsillar leukocytes at low chemokine concentrations. Binding and potentiation of chemokine activity occurs through the C-terminal part of gC ectodomain, containing predicted immunoglobulin-like domains. The mechanism of action of VZV rSgC requires interaction with the chemokine and signalling through the chemokine receptor. Finally, we show that VZV viral particles enhance chemokine-dependent T cell migration and that gC is partially required for this activity. We propose that VZV gC activity facilitates the recruitment and subsequent infection of leukocytes and thereby enhances VZ

Trial Outcome and Associative Learning Signals in the Monkey Hippocampus

In tasks of associative learning, animals establish new links between unrelated items by using information about trial outcome to strengthen correct/rewarded associations and modify incorrect/unrewarded ones. To study how hippocampal neurons convey information about reward and trial outcome during new associative learning, we recorded hippocampal neurons as monkeys learned novel object-place associations. A large population of hippocampal neurons (50%) signaled trial outcome by differentiating between correct and error trials during the period after the behavioral response. About half these cells increased their activity following correct trials (correct up cells) while the remaining half fired more following error trials (error up cells). Moreover, correct up cells, but not error up cells, conveyed information about learning by increasing their stimulus-selective response properties with behavioral learning. These findings suggest that information about successful trial outcome conveyed by correct up cells may influence new associative learning through changes in the cell's stimulus-selective response properties.National Institutes of Health (U.S.) (NIH grant MH48847)National Institutes of Health (U.S.) (NIH Award DA015644)National Institutes of Health (U.S.) (NIH Award MH59733)National Institutes of Health (U.S.) (NIH grant MH071847)National Institutes of Health (U.S.) (NIH grant DP1 OD003646)Fondation pour la recherche médical

Proteomes and Signalling Pathways of Antler Stem Cells

As the only known example of complete organ regeneration in mammals, deer antler in the growing or velvet phase is of major interest in developmental biology. This regeneration event initiates from self-renewing antler stem cells that exhibit pluripotency. At present, it remains unclear how the activation and quiescence of antler stem cells are regulated. Therefore, in the present study proteins that were differentially expressed between the antler stem cells and somatic cells (facial periosteum) were identified by a gel-based proteomic technique, and analysed using Ingenuity Pathway Analysis software. Several molecular pathways (PI3K/Akt, ERK/MAPK, p38 MAPK, etc.) were found to be activated during proliferation. Also expressed were the transcription factors POU5F1, SOX2, NANOG and MYC, which are key markers of embryonic stem cells. Expression of these proteins was confirmed in both cultured cells and fresh tissues by Western blot analysis. Therefore, the molecular pathways and transcription factors identified in the current study are common to embryonic and adult stem cells. However, expression of embryonic stem cell transcription factors would suggest that antler stem cells are, potentially, an intermediary stem cell type between embryonic and the more specialized tissue-specific stem cells like those residing in muscle, fat or from a hematopoietic origin. The retention of this embryonic, pluripotent lineage may be of fundamental importance for the subsequent regenerative capacity of antlers

Does Habitual Physical Activity Increase the Sensitivity of the Appetite Control System? A Systematic Review.

BACKGROUND: It has been proposed that habitual physical activity improves appetite control; however, the evidence has never been systematically reviewed. OBJECTIVE: To examine whether appetite control (e.g. subjective appetite, appetite-related peptides, food intake) differs according to levels of physical activity. DATA SOURCES: Medline, Embase and SPORTDiscus were searched for articles published between 1996 and 2015, using keywords pertaining to physical activity, appetite, food intake and appetite-related peptides. STUDY SELECTION: Articles were included if they involved healthy non-smoking adults (aged 18-64 years) participating in cross-sectional studies examining appetite control in active and inactive individuals; or before and after exercise training in previously inactive individuals. STUDY APPRAISAL AND SYNTHESIS: Of 77 full-text articles assessed, 28 studies (14 cross-sectional; 14 exercise training) met the inclusion criteria. RESULTS: Appetite sensations and absolute energy intake did not differ consistently across studies. Active individuals had a greater ability to compensate for high-energy preloads through reductions in energy intake, in comparison with inactive controls. When physical activity level was graded across cross-sectional studies (low, medium, high, very high), a significant curvilinear effect on energy intake (z-scores) was observed. LIMITATIONS: Methodological issues existed concerning the small number of studies, lack of objective quantification of food intake, and various definitions used to define active and inactive individuals. CONCLUSION: Habitually active individuals showed improved compensation for the energy density of foods, but no consistent differences in appetite or absolute energy intake, in comparison with inactive individuals. This review supports a J-shaped relationship between physical activity level and energy intake. Further studies are required to confirm these findings. PROSPERO REGISTRATION NUMBER: CRD42015019696

In Vivo Imaging of Transiently Transgenized Mice with a Bovine Interleukin 8 (CXCL8) Promoter/Luciferase Reporter Construct

One of the most remarkable properties of interleukin 8 (CXCL8/IL-8), a chemokine with known additional functions also in angiogenesis and tissue remodeling, is the variation of its expression levels. In healthy tissues, IL-8 is barely detectable, but it is rapidly induced by several folds in response to proinflammatory cytokines, bacterial or viral products, and cellular stress. Although mouse cells do not bear a clear homologous IL-8 gene, the murine transcriptional apparatus may well be capable of activating or repressing a heterologous IL-8 gene promoter driving a reporter gene. In order to induce a transient transgenic expression, mice were systemically injected with a bovine IL-8 promoter–luciferase construct. Subsequently mice were monitored for luciferase expression in the lung by in vivo bioluminescent image analysis over an extended period of time (up to 60 days). We demonstrate that the bovine IL-8 promoter–luciferase construct is transiently and robustly activated 3–5 hours after LPS and TNF-α instillation into the lung, peaking at 35 days after construct delivery. Bovine IL-8 promoter–luciferase activation correlates with white blood cell and neutrophil infiltration into the lung. This study demonstrates that a small experimental rodent model can be utilized for non-invasively monitoring, through a reporter gene system, the activation of an IL-8 promoter region derived from a larger size animal (bovine). This proof of principle study has the potential to be utilized also for studying primate IL-8 promoter regions