Role of CD36 in Obesity-Associated Fatty Liver Disease and Hepatic Insulin Resistance

Dmitri Samovski, Ph.D.

Project Summary:

Obesity associates with continuous exposure of liver to high levels of fats, which over time induces abnormal fat accumulation in liver cells and leads to fatty liver and tissue malfunction. Eventually these changes can result in insulin resistance and Type 2 diabetes. The molecular causes that initiate this cycle of negative events remain unclear. I have discovered a novel molecular pathway that serves to adjust liver fat breakdown to fat supply, which maintains energy balance and normal function. I am proposing to examine if disruption of this pathway results in abnormal fat handling that is detrimental to liver health.


I have discovered that high fat regulate the function of AMPK and PI3K, intracellular proteins that are master coordinators of liver energy utilization. High fat alters the association between proteins important for proper function of AMPK and PI3K. The specific questions I will ask are:

1.    How does high fat regulate AMPK and PI3K?

2.    Does obesity alter communication between the proteins involved in AMPK and PI3K function?

3.    Does this cause disruption of cellular energy metabolism and insulin resistance?


I will use liver cells and mice with altered liver levels of proteins that are important for regulation of AMPK and PI3K function. I anticipate my study will provide novel insights into the molecular mechanisms that link obesity to the development of abnormal liver function. The findings should allow the design of therapeutic approaches that can target the link between CD36 and AMPK to enhance fat breakdown by liver and decrease liver fat accumulation.