H2020Индивидуална стипендия2019–2021

Hepatic Thermogenesi · Study the functions of the hepatic sympathetic nerve and the receptor Adrb3 in liver-mediated adaptive thermogenesis.

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-08-01 → 2021-07-31
Финансиране от ЕС: 203 149 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Черният дроб и ролята на симпатичния нерв и рецептора Adrb3 се изследват като нов източник на производство на топлина в тялото. Разбирането на този процес може да помогне при лечението на затлъстяването и различни метаболитни нарушения.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Study the functions of the hepatic sympathetic nerve and the receptor Adrb3 in liver-mediated adaptive thermogenesis.

The global epidemic of obesity is related to an unbalanced energy intake. Indeed, obesity results when the intake of energy exceeds that which is expended with the resultant storage of the excess energy as fat. Thermogenesis, the metabolic expenditure of energy as heat, is the primary way in which mammals lose dietarily-derived energy and some evidence suggests that certain obese humans may have defective thermogenesis. In small mammals, like rodents, the primary site of thermogenesis is thought to be in brown adipose tissue, a modified adipose tissue specialized in lipid burning as opposed to the lipid-storing function of white adipose tissue. Unfortunately, the activation of thermogenesis in human adipose tissues as a therapeutic approach to fight obesity proved to be largely disappointing. Among the probable causes of discrepancy with animal research, one should list the possible differences in mechanisms regulating thermogenesis in humans and rodents. With this in mind, this proposal intended to demonstrate the existence of a novel site of heat production and energy expenditure in the liver with the hope that this hepatic thermogenesis could be used in humans to treat various metabolic disorders.

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

Цел на проекта

Core body temperature is among the best-guarded constants in homeothermic species. It results from the evolution of physiological mechanisms capable of regulating the production as well as the exchange of heat with the environment. The objective of my proposal is to define a new role for the liver in adaptive thermogenesis whereby the liver will be involved in heat production under the regulation of the hepatic sympathetic nerve. I will first ascertain that the liver can generate extra heat when adaptive thermogenesis is triggered (Aim 1). Hepatic adaptive thermogenesis will be demonstrated using a combination of interdisciplinary, cutting-edge technologies normally applied to the fields of physics and chemistry. I will then determine the molecular foundation of this hepatic heat production (Aim 2). For this purpose, OMICs data (transcriptomic, proteomic and metabolomics) will be generated from cold-exposed liver tissues in order to identify: (1) the hepatic molecular heating mechanism; (2) the expected metabolic rewiring necessary to sustain prolonged heat production from thermogenic hepatocytes. Finally, I will study how hepatic adaptive thermogenesis is regulated by the hepatic sympathetic nerve at the anatomical level and by the adrenergic receptor Adrb3 at the molecular level (Aim 3). For this purpose, I will use a combination of surgical (hepatic sympathectomy) and genetic (generation of liver-specific beta-adrenergic receptor 3 knockout mice) ablation techniques. Longstanding observations, together with my own preliminary results argue for this existence of hepatic adaptive thermogenesis and its molecular characterization would certainly represent a major breakthrough for both our fundamental understanding of homoeothermic physiology as well as for future clinical applications. Demonstrating that the liver is involved in adaptive thermogenesis would certainly open new avenues for the treatment of nonalcoholic fatty liver disease, a major disease in Europe.

Оригинален текст от CORDIS (на английски).

Участници

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE · LausanneКоординаторШвейцария