MILER · Exploring the underlying mechanIsms of partial leptin reduction towards a non-invasive obesity therapy
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2022-04-01 → 2025-03-31
- Финансиране от ЕС
- 284 345 €
- Участници
- 2
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Частичното намаляване на хормона лептин се изучава като средство за борба с затлъстяването. Това е важно, защото помага за разработването на по-ефективни методи за сваляне на теглото и намаляване на риска от диабет и сърдечни заболявания.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Exploring the underlying mechanIsms of partial leptin reduction towards a non-invasive obesity therapy
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.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Leptin regulates energy balance by functioning as a “satiety signal”. When identified 26 years ago, expectations were high that leptin therapies could be used for the treatment of obesity. In contrast to the successful use of leptin for treatment of individuals with lipodystrophy and complete leptin deficiency, pharmacological approaches using leptin therapy for the treatment of diet-induced obesity have been widely unsuccessful. Injecting recombinant leptin in the context of obesity, associated with elevated leptin levels, remains ineffective as central neurons become leptin resistant. Interestingly, Scherer et al. recently published a series of findings that encourages for a conceptual shift. They reported that a partial reduction of circulating leptin levels in the obese state prompts an unexpected systemic response resulting in weight loss, reduced food intake, improved glucose and insulin tolerance and increased energy expenditure - all consistent with leptin re-sensitization in central neurons. The systemic physiological benefits of partial leptin reduction have already been demonstrated. The overall goal of this proposal is therefore to determine the underlying molecular mechanisms that are induced by leptin reduction and trigger leptin re-sensitization. Understanding of these conceptual steps should lead us to explore partial leptin reduction as a viable avenue for anti-obesity and anti-diabetic therapy in the near future. We aim to determine the peripheral effects of leptin reduction using neutralizing leptin antibodies and advanced mouse genetics. Moreover, we will determine downstream signaling events that are affected in peripheral tissues upon leptin depletion using imaging mass cytometry and transcriptional regulation by single cell RNAseq. Finally, we will also determine whether leptin lowering offers synergistic effects with existing weight loss approaches and whether anti-diabetic interventions rely on leptin lowering independent of weight loss.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITETET I BERGEN · BergenКоординаторНорвегия
- THE UNIVERSITY OF TEXAS SYSTEM · AustinСъединени щати
Връзки
Данни: CORDIS, © Европейски съюз