Novel Hepatic-Adipose Tissue Crosstalk Regulates Body Weight
Abstract
Diabetes is one of the leading cause of death in the United States. It is a complicated disease caused by multiple factors. Aging and obesity are the most universal contributors to diabetes. 83% of Department of Defense beneficiaries and 78% of Veterans are overweight or obese. Nearly one in four military Veterans (24%) have diabetes, more than double the 9.4% incidence in the entire U.S. population. The prevalence of diabetes in Veterans and the general population is increasing rapidly, creating enormous social and economic burdens. Diabetics develop a variety of debilitating metabolic complications such as retinopathy, nephropathy, and cardiovascular diseases, which costs more than $176 billion in direct medical treatments and $69 billion in productivity loss. Despite the availability and effectiveness of lifestyle changes, many medications, and even aggressive surgical treatments, diabetes remains a huge problem. In this proposal, we will identify a novel liver-secreted hormone (called a hepatokine) that reprograms fat tissues to utilize more energy, especially fatty acids. This liver-fat tissue crosstalk is originally found in a mouse model of liver injury, which exhibits lower body weight and improved glucose/insulin resistance through reprogramming of fat tissue metabolism. We predicted that a hepatokine could mediate anti-obesity and anti-diabetes effects in this model, as a natural self-defense mechanism affecting other tissues to reduce inflammatory damage, to shift energy metabolism, and to improve metabolic stress. To identify this hormone, we used gene expression and protein profiling and found orosomucoid 2 (ORM2) as a putative hepatokine that could mediates many metabolically beneficial effects. We will investigate how Orm2 expression is regulated and what the cellular responses to ORM2 treatment are. Metabolic effects of ORM2 will be tested in obese and diabetic mice. By integrating the ORM2 regulatory mechanisms and metabolic function, this research will provide insight into the potential therapeutic strategies for this novel hepatokine in obesity and diabetes.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810126
Entities
People
- Kangho Kim
Organizations
- Baylor College of Medicine
- United States Army