Details
- ERC sector
- LS4 - Physiology in Health, Disease and Ageing
- ERC subsector
- LS4_9 - Metabolism and metabolic disorders, including diabetes and obesity
- Project start date
- CUP
- D53D23014570006
- Financial support received
- €79.378,00
Description and purpose
In this proposal, our overall aim is to advance the understanding of how diet composition, energy metabolism, sympathetic nervous system, and sex are interlinked in the pathogenesis of metabolic syndrome by tackling several knowledge gaps and uncovering pathways that could be targeted by novel therapies. There are three specific aims: Aim 1 focuses on the systemic and cellular metabolic effects of amino-acid substituted diets in male and female mice; Aim 2 focuses on how sex differences influence the responses of the adipose organ to amino-acid manipulated diet affecting the sympathetic innervation of thermogenic fat; Aim 3 focuses on whether sex and diets influence neuronal and non-neuronal cholinergic systems modulating energy expenditure and systemic metabolism.
Purpose
Metabolic syndrome is a cluster of diseases that occur together, increasing the risk of type 2 diabetes, heart disease, stroke, and tumors; it can also be encountered in the elderly due to metabolic ageing. Sex plays a relevant role in the metabolic syndrome risk, yet multiple aspects of this relationship remain unexplained with consequences in prevention and treatment. A major cause of metabolic diseases is excess body fat in the abdomen, increased waist circumference (visceral obesity), and ectopic fat accumulation in the liver (leading to non-alcoholic fatty liver disease). Visceral obesity is increasingly common, and one-third of Western populations—including children— have BMI greater than 30. Although women have higher fat mass than men, the prevalence of the metabolic syndrome is lower in premenopausal women but higher in postmenopausal women than in men at a similar age. Thus, it is paramount to develop improved and personalized therapies and reduce the enormous, growing burdens of obesity and metabolic syndrome on society worldwide.
Expected results
We expect to identify the mechanism of the beneficial metabolic effect of amino-acid manipulated diets and to describe any instance of sex-dependent effect. We also expect to confirm the mouse data with in vitro translational work with human-mased 3D organoids.
Achieved results
My research unit at Unipr worked collaboratively with the Unit of Unimi and focused on Aim 1 to determine the systemic and tissue metabolic effects of designer diets, in which proteins are substituted with original mixtures of free amino acids, in male and female mice by measuing tissue levels of various metabolically-relevant pathways including uncloupling, insulin signaling, senescence and inflammation. We also tested the effect of amino-acids mixtures on senescence induction and inflammationin human mesenchimal stromal cell derived 2Dand 3D cultures.
Scientific director
Modified on