Adipose tissue plasticity and gut microbiota in obesity and insulin resistance.
Welcome to the homepage of the Laboratory of Metabolic Diseases. The main interests of our lab are the molecular mechanisms underlining metabolic diseases, primarily obesity and insulin resistance. Mammals have two types of fat: brown and white, with opposing functions. The white fat is an important regulator of the whole body homeostasis that also serves to store energy in the form of triglycerides. The main function of the brown fat is to burn lipids in order to produce heat, a function that can be induced by cold exposure or diet. Recent evidence strongly supports the existence of functional brown fat in adult humans. Promotion of increased brown fat development in humans and experimental mice leads to increased energy expenditure without causing dysfunction in other tissues, suggesting the manipulation of the fat stores as an important therapeutic objective. Recent data indicate that miRNAs, a novel class of evolutionarily conserved regulatory RNA molecules, have a key role in modulating cell differentiation and metabolism of different tissue types, including adipocytes (fat cells).
The first part of our research aims at identifying metabolically active miRNAs and factors, and investigating their roles in animal models of obesity (primarily mice and rats), as well as in primary cultures of precursor cells using systems biology and targeted approaches. We will also generate tools that will enable us to screen for drugs and peptides involved in brown and white adipose tissue differentiation and function, use lineage tracing studies to identify the origin of the brown adipocytes, and develop rational strategies to enable miRNA delivery and silencing specifically in the brown fat.
The second part of our research is focused on the role of the gut microbiota in the development of metabolic diseases, primarily dyslipidaemia and insulin resistance, and in particular the response of the host to the changes in the gut microbiota composition. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota and the host response to combat disease and improve health.
In summary, with our research we aim at identifying miRNAs and other factors that regulate BAT and WAT differentiation and function, and at characterizing the host response to the changes of the gut microbiota composition. Using mice as model organism, as well as in vitro systems, cohorts of human patients, and linage tracing studies we aim at determining the origin of the brown (beige) fat cells within the white adipose tissue, at establishing their importance in the regulation of metabolism in vivo, and at developing novel strategies to induce brown fat differentiation and function. In addition, discovering ways to exclusively deliver and silence miRNAs in fat/brown fat will allow us not only to investigate the miRNA function specifically in the brown fat, but also to develop new strategies for treatment of dyslipedaemia, diabetes and obesity.
For further reading please see the Publications from our lab
Left to right: Obese and lean mouse model (Left). Graphical representation: Mature brown and white fat cells originate from precursor cells (preadipocytes) (Middle). Fluorescent imaging of fat cells differentiation (Right). It is not known whether there are different preadipocyte populations between the white and the beige fat, and what regulates the differentiation to either cell type.