High-intensity exercise increases breast milk adiponectin concentrations: a randomised cross-over study

IntroductionAdiponectin plays a role in glucose and fat metabolism and is present in human breast milk. It has been postulated that higher breast milk adiponectin concentrations may prevent rapid weight gain in infancy. Prior research indicates that circulating adiponectin increases acutely after endurance exercise, but no prior research has investigated the effect of exercise on breast milk adiponectin concentrations. The purpose of this randomised, cross-over study was to determine the acute effects of endurance exercise on adiponectin concentrations in human breast milk.MethodsParticipants who were exclusively breastfeeding a 6–12 week-old term infant (N = 20) completed three conditions in the laboratory: (1) Moderate-intensity continuous training (MICT), (2) High-intensity interval training (HIIT), and (3) No activity (REST). At each condition, we collected breast milk at 07:00 h (before exercise/rest), 11:00 h (immediately after exercise/rest), 12:00 h (1 h after exercise/rest), and 15:00 h (4 h after exercise/rest) and determined adiponectin concentrations using enzyme-linked immunosorbent assay. We compared changes in adiponectin concentrations after MICT and HIIT, adjusted for the morning concentration on each test day, with those after REST, using paired t-tests.ResultsAdiponectin concentrations increased 1 h after HIIT, from 4.6 (± 2.2) μg/L in the 07:00 h sample to 5.6 (± 2.6) μg/L. This change was 0.9 μg/L (95% confidence interval 0.3 to 1.5) greater than the change between these two timepoints in the REST condition (p = 0.025). There were no other statistically significant changes in adiponectin concentrations.ConclusionHIIT may increase adiponectin concentrations in breast milk acutely after exercise. Further studies should determine the impact of exercise-induced elevations in breast milk adiponectin concentrations on growth and metabolism in infancy

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Motivasjon og incentivsystemer i salgsbransjen

Dagens fokus på motivasjon og incentiver i arbeidslivet har oss til å velge dette som tema for vår siviløkonomutredning. En stor aktør innen elektronikkbransjen har gitt oss i oppdrag å analysere bedriftens incentivstruktur og dennes innvirkning på de ansattes motivasjon. Som bakgrunn har vi først presentert ulike teorier om begrepet motivasjon, hvoretter det følger en redegjørelse og drøfting av fordeler og ulemper ved ulike incentiver. Vi har dessuten diskutert effekter av ytre belønning på ansattes indre motivasjon. Videre har vi utformet seks hypoteser med basis teori og informasjon fra bedriften. Gjennom en spørreundersøkelse rettet mot bedriftens ansatte og deretter ved hjelp av mediantesten, fant vi at to av de seks hypotesene måtte forkastes; verken bonussystemet eller karrieremuligheter hadde positiv innvirkning på arbeidsinnsatsen. En kritisk begrensning ved resultatene våre var de ansattes motvilje mot å oppgi stillingsbrøk, kjønn og avdeling. Dette kan ha hatt innvirkning på hypotesetestens utfall

The immune checkpoint regulator PD-L1 is a specific target for naturally occurring CD4(+) T cells

Programmed cell death 1 ligand 1 (PD-L1) is an important regulator of T-cell responses and may consequently limit anticancer immunity. We have recently identified PD-L1-specific, cytotoxic CD8(+) T cells. In the present study, we develop these findings and report that CD4(+) helper T cells spontaneously recognize PD-L1. We examined the locality of a previously identified HLA-A*0201-restricted PD-L1-epitope for the presence of possible CD4(+) T-cell epitopes. Thus, we identified naturally occurring PD-L1-specific CD4(+) T cells among the peripheral blood lymphocytes of cancer patients and - to lesser extents - healthy donors, by means of ELISPOT assays. PD-L1-specific CD4(+) T cells appeared to be T(H)17 cells exhibiting an effector T-cell cytokine profile. Hence, PD-L1-specific CD4(+) T cells released interferon γ (IFNγ), tumor necrosis factor α (TNFα) and interleukin-17 (IL-17) in response to a long PD-L1-derived peptide. Furthermore, we demonstrate that the specific recognition of PD-L1 by CD4(+) T cells is MHC class II-restricted. Natural T-cell responses against PD-L1 are noteworthy as they may play a prominent role in the regulation of the immune system. Thus, cytokine release from PD-L1-specific CD4(+) T cells may surmount the overall immunosuppressive actions of this immune checkpoint regulator. Moreover, PD-L1-specific T cells might be useful for anticancer immunotherapy, as they may counteract common mechanisms of immune escape mediated by the PD-L1/PD-1 pathway

Tryptophan 2,3-dioxygenase (TDO)-reactive T cells differ in their functional characteristics in health and cancer

Tryptophan-2,3-dioxygenase (TDO) physiologically regulates systemic tryptophan levels in the liver. However, numerous studies have linked cancer with activation of local and systemic tryptophan metabolism. Indeed, similar to other heme dioxygenases TDO is constitutively expressed in many cancers. In the present study, we detected the presence of both CD8(+) and CD4(+) T-cell reactivity toward TDO in peripheral blood of patients with malignant melanoma (MM) or breast cancer (BC) as well as healthy subjects. However, TDO-reactive CD4(+) T cells constituted distinct functional phenotypes in health and disease. In healthy subjects these cells predominately comprised interferon (IFN)γ and tumor necrosis factor (TNF)-α producing Th1 cells, while in cancer patients TDO-reactive CD4(+) T-cells were more differentiated with release of not only IFNγ and TNFα, but also interleukin (IL)-17 and IL-10 in response to TDO-derived MHC-class II restricted peptides. Hence, in healthy donors (HD) a Th1 helper response was predominant, whereas in cancer patients CD4(+) T-cell responses were skewed toward a regulatory T cell (Treg) response. Furthermore, MM patients hosting a TDO-specific IL-17 response showed a trend toward an improved overall survival (OS) compared to MM patients with IL-10 producing, TDO-reactive CD4(+) T cells. For further characterization, we isolated and expanded both CD8(+) and CD4(+) TDO-reactive T cells in vitro. TDO-reactive CD8(+) T cells were able to kill HLA-matched tumor cells of different origin. Interestingly, the processed and presented TDO-derived epitopes varied between different cancer cells. With respect to CD4(+) TDO-reactive T cells, in vitro expanded T-cell cultures comprised a Th1 and/or a Treg phenotype. In summary, our data demonstrate that the immune modulating enzyme TDO is a target for CD8(+) and CD4(+) T cell responses both in healthy subjects as well as patients with cancer; notably, however, the functional phenotype of these T-cell responses differ depending on the respective conditions of the host