6533b862fe1ef96bd12c5fbc

RESEARCH PRODUCT

Role of LECT2 in non alcoholic fatty liver disease

subject

description

The liver is the privileged site of metabolic regulations that must be tightly coordinated to prevent metabolic imbalance to preserve homeostasis. Alteration of these processes can promote steatosis, an essential feature of Non-Alcoholic Fatty Liver Diseases (NAFLD), representing the new global epidemic threat. During this thesis work, we demonstrated that LECT2, a liver secreted factor, is increased in both Human and mice harboring fatty liver. In a physiological context, we demonstrated that LECT2 controls liver lipogenesis through the LXR signalling pathway. At the molecular level, the absence of LECT2 induces a specific accumulation of 25-OHC oxysterol which leads to a significant increase in the activity of LXR and its target genes. From a mechanistic point of view, hepatospecific re-expression of LECT2 in Lect2-deficient mice is sufficient to specifically decrease the activity of LXR and the expression of its target genes. These results demonstrate that Lect2 behaves as a regulator of LXR signaling in the liver and illustrate that LECT2 is a key player in hepatic lipogenesis. Taken together, our results suggest that LECT2 is a key player in NAFLD, and open up new diagnostic and therapeutic perspectives for these diseases.