Page 8 - N. Metabolism and metabolic diseases

[N. Metabolism and metabolic diseases-4]

Intravital imaging of dynamic hepatic microenvironment

during the progression of NAFLD in MCD diet-induced

mouse model

Jieun Moon¹˙², Eunji Kong²˙³, Pilhan Kim¹˙²˙³˙*

¹Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon

34141, Korea, ²KI for Health Science and Technology (KIHST), Korea Advanced Institute of Science and Technology,
Daejeon 34141, Korea, ³Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science

and Technology, Daejeon 34141, Korea

Nonalcoholic fatty liver disease (NAFLD) is a rapidly increasing chronic liver disorder worldwide. The pathogenesis
of NAFLD begins with hepatic steatosis, accumulation of lipid droplets in hepatocytes, which then can progress to

nonalcoholic steatohepatitis (NASH), cirrhosis, and ultimately cancer. Whereas steatosis stage is considered as
reversible, NASH has a significantly increased risk to lead to more severe stages such as cirrhosis and cancer.

Unfortunately, effective treatment strategy of NASH has remained elusive and improved understanding of underlying
mechanism in the transition from steatosis to NASH is highly needed. Currently, histopathological analysis is gold

standard to define the stage of NAFLD. However, this analysis provides only static 2D information, which overlooks
dynamic pathophysiological changes in hepatic microenvironment. In this study, using a custom-built intravital two-

photon and confocal microscopy system, we successfully achieved longitudinal 3D subcellular-level visualization and
analysis of dynamic hepatic microenvironment such as gradual accumulation of hepatic lipid droplet, topological

alteration of sinusoids, collagen deposition in perisinusoid, and infiltrated macrophage engulfing cellular debris in
the transition from steatosis to NASH.