Type 2 diabetes is a complex metabolic disease closely associated with obesity and characterized, in particular, by a reduced response of tissues to insulin, known as insulin resistance. Skeletal muscle, liver, and adipose tissue play major roles in maintaining glucose homeostasis and are particularly affected by this impairment.
Bioactive lipids and insulin resistance
For many years, our research has aimed to understand how excess lipids can interfere with insulin action. Beyond the simple storage of fat within tissues, certain lipid molecules have genuine signaling functions and can profoundly alter cellular function.
Our team is particularly interested in sphingolipids, a family of bioactive lipids that includes ceramides and sphingosine-1-phosphate (S1P). These molecules are involved in numerous cellular processes, and their metabolism is profoundly altered in obesity, insulin resistance, and type 2 diabetes.
Our work has contributed to showing that the accumulation of specific ceramide species can impair insulin signaling in muscle and adipose cells. It has also highlighted the importance of regulating the metabolism and intracellular transport of these lipids in determining their biological effects.
From lipid abundance to lipid localization
We are now seeking to go beyond simply measuring the total amount of ceramides present in a cell or tissue.
A central question in our research is to understand where these lipids are produced, where they accumulate, and how they move between different cellular compartments. Their localization within specific membranes or cellular domains may be just as important as their concentration in determining their effects on signaling and metabolism.
This approach leads us to investigate the mechanisms controlling sphingolipid synthesis, remodeling, transport, and subcellular organization, as well as their interactions with signaling pathways involved in the insulin response.
From cellular metabolism to inter-organ communication
Our research has also expanded to investigate metabolic communication between organs.
Skeletal muscle and liver are two major areas of our work. In particular, we seek to understand how changes in lipid metabolism within one tissue can influence insulin sensitivity in other tissues.
We therefore investigate the different forms in which lipids can circulate throughout the body and contribute to communication between organs. This approach allows us to integrate the cell biology of sphingolipids into a broader view of the regulation of glucose and lipid metabolism.
An integrated approach to lipotoxicity
To address these questions, we combine several complementary approaches: cell and molecular biology, signaling analysis, lipidomics, imaging, in vivo experimental models, and studies using human models or samples.
The overall goal of our team is to understand how the nature, localization, and circulation of bioactive lipids determine their effects on insulin action and metabolic homeostasis.
Ultimately, a better understanding of these mechanisms may help identify new markers of metabolic dysfunction and new strategies to limit the consequences of lipotoxicity associated with obesity and type 2 diabetes.
