New pharmacological perspectives for the leptin receptor in the treatment of obesity

International audienceAfter its discovery in 1994, leptin became the great hope as an anti-obesity treatment based on its ability to reduce food intake and increase energy expenditure. However, treat-ing obese people with exogenous leptin was unsuccessful in most cases since most of them present already high circulating leptin levels to which they do not respond anymore defining the so-called state of "leptin resistance." Indeed, leptin therapy is unsuccessful to lower body weight in commonly obese people but effective in people with rare single gene mutations of the leptin gene. Consequently, treatment of obese people with leptin was given less attention and the focus of obesity research shifted toward the prevention and reversal of the state of leptin resistance. Many of these new promising approaches aim to restore or sensitize the impaired function of the leptin receptor by pharmacological means. The current review will focus on the different emerging therapeutic strategies in obesity research that are related to leptin and its receptor

William (Bill) Peterson's contributions to ocean science, management, and policy

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Schwing, F. B., Sissenwine, M. J., Batchelder, H., Dam, H. G., Gomez-Gutierrez, J., Keister, J. E., Liu, H., & Peterson, J. O. William (Bill) Peterson's contributions to ocean science, management, and policy. Progress in Oceanography, 182, (2020): 102241, doi:10.1016/j.pocean.2019.102241.In addition to being an esteemed marine ecologist and oceanographer, William T. (Bill) Peterson was a dedicated public servant, a leader in the ocean science community, and a mentor to a generation of scientists. Bill recognized the importance of applied science and the need for integrated “big science” programs to advance our understanding of ecosystems and to guide their management. As the first US GLOBEC program manager, he was pivotal in transitioning the concept of understanding how climate change impacts marine ecosystems to an operational national research program. The scientific insight and knowledge generated by US GLOBEC informed and advanced the ecosystem-based management approaches now being implemented for fishery management in the US. Bill held significant leadership roles in numerous international efforts to understand global and regional ecological processes, and organized and chaired a number of influential scientific conferences and their proceedings. He was passionate about working with and training young researchers. Bill’s academic affiliations, notably at Stony Brook and Oregon State Universities, enabled him to advise, train, and mentor a host of students, post-doctoral researchers, and laboratory technicians. Under his collegial guidance they became critical independent thinkers and diligent investigators. His former students and colleagues carry on Bill Peterson’s legacy of research that helps us understand marine ecosystems and informs more effective resource stewardship and conservation

The ABCs and beyond: Developing an operations research agenda on comprehensive behavior change approaches for HIV prevention: Report from a technical meeting

In April 2003, the Horizons Program sponsored a one-day technical meeting to develop and set priorities for an operations research agenda to study effective behavior change strategies for HIV risk reduction, particularly those that focus on the “ABC” behaviors: abstinence or delaying sex, being faithful or partner reduction, and condom use. Representatives from more than 20 organizations and programs involved in prevention research and programming discussed epidemiological, behavioral, psychosocial, and structural factors that may help determine the effectiveness of promoting the ABCs and other prevention programs. During the meeting, specific opportunities for collaborations and areas of particular interest for each group were discussed, with the goal of permitting each organization to focus on its strengths while working together toward similar outcomes. As noted in this report, the Horizons partnership plans to pursue some of the key operations research questions that were identified by the technical experts

Fra modermælk til donormælk: Forhandlinger af mælk, individ og velfærdskollektiv

Denne artikel udforsker de socio-materielle praksisser, der etablerer donormælk som en sikker substans, der kan cirkulere inden for det danske velfærdssamfund. Studiet tager afsæt i etnografisk feltarbejde i Kvindemælkcentralen på Hvidovre Hospital, hvor arbejdet med donormælk til danske neonatalafdelinger foregår. Det er en arbejdsplads med få ansatte, men med et slutprodukt, som er af livsvigtig karakter for præmature børn, hvis mødre ofte har svært ved at etablere en mælkeproduktion, særligt de første dage efter fødsel. Med inspiration fra ideen om multipel topologi samt antropologiske studier af forbundethed analyserer artiklen hvilke forhold, der gør udvekslingen af mælk fra donormødre til præmature børn mulig. På baggrund af interviews med personale, donormødre og mødre til for tidligt fødte børn viser vi, hvordan de ansatte i Kvindemælkcentralen arbejder med at præsentere donormælk som både en naturlig kropslig substans og et standardiseret produkt uden spor af donorens krop. Artiklen giver indsigt i donernes placering i et forpligtende fællesskab forvaltet af Kvindemælkcentralen og demonstrerer samtidig Kvindemælkcentralens centrale position i arbejdet med at hjælpe præmature og syge børn. Vi argumenterer for, at Kvindemælkcentralens ansatte forvalter, balancerer og afgrænser kontakten mellem donor og modtager - et arbejde, som gør det muligt for modermælk at cirkulere og forbinde nyfødte borgere til velfærdskollektivet

Evaluation of hearing levels and vestibular function and the impact on cognitive performance in (pre)-symptomatic patients with DFNA9:Protocol for a prospective longitudinal study (Rosetta study)

Introduction: Untreated hearing loss is the largest potentially modifiable risk factor for dementia. Additionally, vestibular dysfunction has been put forward as a potential risk factor for accelerated cognitive decline. Patients with Deafness Autosomal Dominant 9 (DFNA9) present with progressive sensorineural hearing loss and bilateral vestibulopathy and show significantly worse results in cognitive performance compared with a cognitively healthy control group. This highlights the need for adequate treatment to prevent further cognitive decline. This study aims to determine how hearing and vestibular function evolve in (pre-)symptomatic carriers of the p.Pro51Ser mutation in the COCH gene and how this impacts their cognitive performance and health-related quality of life.Methods and analysis: A prospective, longitudinal evaluation of hearing, vestibular function and cognitive performance will be acquired at baseline, 1-year and 2-year follow-up. A total of 40 patients with DFNA9 will be included in the study. The study will be a single-centre study performed at the ORL department at the Antwerp University Hospital (UZA), Belgium. The control group will encompass cognitively healthy subjects, already recruited through the GECkO study. The primary outcome measure will be the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for the Hearing-Impaired total score. Secondary outcome measures include Cortical Auditory-Evoked Potentials, vestibular assessments and health-related quality of life questionnaires. The expected outcomes will aid in the development of gene therapy by providing insight in the optimal time window for the application of gene therapy for the inner ear.Ethics and dissemination: The ethical committee of UZA approved the study protocol on 19 December 2022 (protocol number B3002022000170). All participants have to give written initial informed consent in accordance with the Declaration of Helsinki. Results will be disseminated to the public through conference presentations, lectures and peer-reviewed scientific publications.</p

Evaluation of hearing levels and vestibular function and the impact on cognitive performance in (pre)-symptomatic patients with DFNA9:Protocol for a prospective longitudinal study (Rosetta study)

Introduction: Untreated hearing loss is the largest potentially modifiable risk factor for dementia. Additionally, vestibular dysfunction has been put forward as a potential risk factor for accelerated cognitive decline. Patients with Deafness Autosomal Dominant 9 (DFNA9) present with progressive sensorineural hearing loss and bilateral vestibulopathy and show significantly worse results in cognitive performance compared with a cognitively healthy control group. This highlights the need for adequate treatment to prevent further cognitive decline. This study aims to determine how hearing and vestibular function evolve in (pre-)symptomatic carriers of the p.Pro51Ser mutation in the COCH gene and how this impacts their cognitive performance and health-related quality of life.Methods and analysis: A prospective, longitudinal evaluation of hearing, vestibular function and cognitive performance will be acquired at baseline, 1-year and 2-year follow-up. A total of 40 patients with DFNA9 will be included in the study. The study will be a single-centre study performed at the ORL department at the Antwerp University Hospital (UZA), Belgium. The control group will encompass cognitively healthy subjects, already recruited through the GECkO study. The primary outcome measure will be the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for the Hearing-Impaired total score. Secondary outcome measures include Cortical Auditory-Evoked Potentials, vestibular assessments and health-related quality of life questionnaires. The expected outcomes will aid in the development of gene therapy by providing insight in the optimal time window for the application of gene therapy for the inner ear.Ethics and dissemination: The ethical committee of UZA approved the study protocol on 19 December 2022 (protocol number B3002022000170). All participants have to give written initial informed consent in accordance with the Declaration of Helsinki. Results will be disseminated to the public through conference presentations, lectures and peer-reviewed scientific publications.</p

Nocturnal Activation of Melatonin Receptor Type 1 Signaling Modulates Diurnal Insulin Sensitivity via Regulation of Pi3k Activity

Recent genetic studies have highlighted the potential involvement of melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) in the pathogenesis of type 2 diabetes. Here, we report that mice lacking MT1 (MT1 KO) tend to accumulate more fat mass than WT mice and exhibit marked systemic insulin resistance. Additional experiments revealed that the main insulin signaling pathway affected by the loss of MT1 was the activation of phosphatidylinositol-3-kinase (PI3K). Transcripts of both catalytic and regulatory subunits of PI3K were strongly downregulated within MT1 KO mice. Moreover, the suppression of nocturnal melatonin levels within WT mice, by exposing mice to constant light, resulted in impaired PI3K activity and insulin resistance during the day, similar to what was observed in MT1 KO mice. Inversely, administration of melatonin to WT mice exposed to constant light was sufficient and necessary to restore insulin-mediated PI3K activity and insulin sensitivity. Hence, our data demonstrate that the activation of MT1 signaling at night modulates insulin sensitivity during the day via the regulation of the PI3K transcription and activity. Lastly, we provide evidence that decreased expression of MTNR1A (MT1) in the liver of diabetic individuals is associated with poorly controlled diabetes