Exploring the underlying mechanIsms of partial leptin reduction towards a non-invasive obesity therapy

Informazioni relative al progetto

MILER

ID dell’accordo di sovvenzione: 101026295

DOI

10.3030/101026295

Progetto concluso il 28 Febbraio 2025

Data della firma CE 1 Marzo 2021

Data di avvio 1 Aprile 2022

Data di completamento 31 Marzo 2025

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 284 345,28

Contributo UE

€ 284 345,28

Coordinato da

UNIVERSITETET I BERGEN
Norway

Periodic Reporting for period 2 - MILER (Exploring the underlying mechanIsms of partial leptin reduction towards a non-invasive obesity therapy)

Periodo di rendicontazione: 2024-04-01 al 2025-03-31

Sintesi del contesto e degli obiettivi generali del progetto

Obesity is a predominant risk factor for several chronic diseases, including type 2 diabetes, cardiovascular disease, fatty liver disease and cancer. Obesity has become a severe clinical and socioeconomic problem as the prevalence has more than doubled during the last decades, with more than 1.9 billion adults and 41 million children classified as overweight or obese in 2016. Despite surgical, lifestyle alternatives, and some pharmacological treatments, there is a major unfulfilled need of effective interventions to stimulate and sustain weight loss in overweight and obese individuals. The overall objectives of MILER are to explore partial leptin reduction as an avenue to treat obesity and obesity related co-morbidities. We furthermore aim to explore the underlying molecular mechanisms of leptin sensitization in the periphery and pathological conditions. The data obtained this far during project period strengthens the rationale for developing tools to achieve leptin reduction in the context of obesity and obesity-related co-morbidities.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

During the project period we have established several models to assess the effects of leptin reduction. This includes diet-induced obese models as well as transgenic models. We have demonstrated synergistic effects of leptin reduction in combination with existing weight loss/anti-diabetic interventions. Moreover, we have demonstrated a beneficial effect of leptin reduction in relation to treatment for metabolic syndrome associated conditions as well as other obesity-related co-morbidities. After demonstrating promising effects of upon leptin reduction, we have started to characterize the downstream signaling mechanisms. We have set up in vitro modelling systems to study signaling pathways in a cell type specific manner. Additionally, we are studying effect on manipulated leptin levels at a single cell level across different cell types present in the microenvironment.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

The anticipated detailed insights into the “leptin resistance phenomenon” at the single cell, tissue, and systemic level, could completely re-define established mechanisms for leptin signaling. Additionally, understanding of the role of leptin lowering in the context of obesity and obesity-related comorbidities could potentially form the basis of a new treatment strategy of these diseases.

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