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

Project Information

MILER

Grant agreement ID: 101026295

DOI

10.3030/101026295

Project terminated on 28 February 2025

EC signature date 1 March 2021

Start date 1 April 2022

End date 31 March 2025

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 284 345,28

EU contribution

€ 284 345,28

Coordinated by

UNIVERSITETET I BERGEN
Norway

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

Reporting period: 2024-04-01 to 2025-03-31

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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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