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

Información del proyecto

MILER

Identificador del acuerdo de subvención: 101026295

DOI

10.3030/101026295

Proyecto finalizado el 28 Febrero 2025

Fecha de la firma de la CE 1 Marzo 2021

Fecha de inicio 1 Abril 2022

Fecha de finalización 31 Marzo 2025

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 284 345,28

Aportación de la UE

€ 284 345,28

Coordinado por

UNIVERSITETET I BERGEN
Norway

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

Período documentado: 2024-04-01 hasta 2025-03-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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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