HEИндивидуална стипендия2022–2024

MAMllingIR · Endoplasmic Reticulum-Mitochondria contact sites structural and functional adaptation during Insulin Resistance

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2022-07-01 → 2024-06-30
Финансиране от ЕС: 173 847 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Връзката между ендоплазмения ретикулум и митохондриите в клетките се променя при инсулинова резистентност, предизвикана от вредна храна. Разбирането на тези процеси помага да се разбере как се развиват затлъстяването и диабет тип 2.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Endoplasmic Reticulum-Mitochondria contact sites structural and functional adaptation during Insulin Resistance

The rise in obesity and related metabolic disorders is a significant global health crisis, largely driven by lifestyle factors associated with the so-called Western diet. This diet, characterised by high levels of sugar, salt, fat and calories, combined with an increasingly sedentary lifestyle, exposes a large proportion of the world's population to environmental stressors that severely impact metabolic health. One of the most worrying consequences of this lifestyle is the disruption of glucose homeostasis - a critical process that ensures stable blood glucose levels through the coordinated action of various tissues, hormones and neural circuits. Maintaining glucose levels within a narrow, healthy range is essential to provide energy for cells while avoiding harmful spikes or drops in blood glucose. However, in people who are obese, an important complication occurs: the loss of insulin sensitivity in metabolically active tissues such as skeletal muscle and the liver. This condition, known as insulin resistance, leads to elevated blood glucose levels, a hallmark of type 2 diabetes and a major risk factor for other serious health complications. At the heart of this metabolic dysfunction are two intracellular organelles, the endoplasmic reticulum (ER) and mitochondria. These organelles play critical roles in cellular function, but their activities are significantly disrupted by the high-fat, high-calorie Western diet. This disruption affects intracellular signalling processes that are crucial for maintaining cellular function and metabolic balance. Historically, the roles of the ER and mitochondria in the development of metabolic diseases have been studied independently. However, recent research has shown that these organelles are deeply interconnected, both physically and metabolically, through structures known as mitochondria-associated ER membranes (MAMs). These MAMs facilitate direct communication between the ER and mitochondria, supporting inter-organelle signalling that is essential for dynamic metabolic regulation. The primary aim of the project is to investigate and elucidate the role of MAMs in the context of metabolic diseases such as obesity and diabetes. By understanding how miscommunication between the ER and mitochondria contributes to insulin resistance and metabolic dysfunction, the project aims to identify new molecular targets for therapeutic intervention. This research is not only crucial to advancing the scientific understanding of metabolic diseases, but also has significant potential to inform public health strategies and reduce the burden of these diseases on healthcare systems.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The high calory intake and the sedentary behaviours represent one of the most common stress to which humanity is subjected. This is leading to an increased incidence of obesity that can be aggravated by dysfunctional metabolism, among which insulin resistance (IR) is the most common scenario. Two crucial processes know to lead to IR are Endoplasmic Reticulum (ER) stress and mitochondrial dysfunction. Mitochondria and ER are in tight physical contact through the mitochondria-associated ER membranes (MAMs), which are emerging as an important hub for glucose homeostasis. MAMs are involved in a plethora of cell functions, such as lipid synthesis, ROS and Ca2+ signalling, autophagy and inflammation, all processes tightly linked with cellular insulin sensitivity. In support to this notion, MAMs miscommunication was shown to occur in the presence of IR. Nevertheless, no conclusive molecular mechanisms can explain MAMs adaptation during IR. Furthermore, how MAMs remodelling affects the signalling between ER and mitochondria (Ca2+, ROS, lipid exchange) during IR progression and how this affects ER and mitochondria functions are still open questions. The overarching aim of this proposal is to characterize the alterations of intracellular signalling in mouse models of hepatic IR at the level of MAMs and to develop a standardized methodological approach to assess inter-organelles signalling changes during pathophysiological cues. To this goal, I will implement innovative approaches in vivo to quantify these contacts and to identify the MAMs molecular composition during IR. Furthermore, I will characterize the consequence of IR on MAMs signalling pathways by combining ‘omics approaches and imaging technics, to identify the molecular and functional signature of the MAMs during the IR in vivo and characterize new molecular pathways involved in the onset of IR in the liver.

Оригинален текст от CORDIS (на английски).

Участници

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH · NeuherbergКоординаторГермания