Antioxidant and Gene Regulation Laboratory
RESEARCH FOCUSOur research is conducted to address two questions: (1) Why does inflammation occur in obesity? (2) How does inflammation regulate insulin resistance? Obesity-associated inflammation has been well documented for its detrimental activities in the pathogenesis of insulin sensitivity. However, anti-inflammation approaches have not been able to provide solid evidence in clinical trials to support the concept. We believe that this is due to the beneficial activities of inflammation in the body, which have been uncovered by studies in several laboratories including ours.
ABOUT THIS LAB
Obesity-associated inflammation contributes to the pathogenesis of many chronic diseases including type 2 diabetes, metabolic syndrome, fatty liver, and atherosclerosis. Adipose tissue is a primary site of chronic inflammation in obesity. The inflammation is associated with metabolic disorders in glucose and fatty acids. The cellular mechanism is related to inhibition of adipogenesis, induction of adipocyte degeneration, stimulation of lipolysis, and suppression of adiponectin expression. The molecular mechanism involves suppression of transcription factors such as C/EBPs, and PPAR?. Although these negative effects of inflammation have been well documented in the literature, the beneficial activities of inflammation remain largely unknown in obesity. It is not clear whether inflammation plays a role in adipose tissue remodeling and maintenance of energy homeostasis in the body. Our studies suggest that: (a) Inflammation stimulates angiogenesis in adipose tissue during quick tissue expansion; and (b) inflammation enhances energy expenditure in the maintenance of energy homeostasis. These two activities represent the bodys feedback responses to the energy surplus in obesity.
In the first effect, inflammation is derived from a hypoxia response in adipose tissue to amplify the angiogenic signals in the process of compensatory tissue remodeling. We reported that obesity leads to a reduction in oxygen pressure in adipose tissue. The inflammation is induced in adipose tissue after activation of transcription factors such as HIF-1a and NF-kB in response to the hypoxia. Additionally, hypoxia contributes to chronic inflammation by induction of lipolysis and apoptosis in adipocytes. Macrophage infiltration is elevated, and expression of angiogenic factors is enhanced. The concept of adipose tissue hypoxia has been accepted by an increasing number of investigators in the obesity field.
In the second activity, inflammation contributes to the maintenance of energy homeostasis by stimulation of energy expenditure. Different from the local effect in tissue remodeling, this inflammatory activity has a broad impact and is mediated by inflammatory cytokines produced by adipose tissue. This conclusion is derived from phenotype studies of two mouse models of dietary obesity. Chronic inflammation in these models protects both lines of transgenic mice from obesity and insulin resistance when fed a high-fat diet. The mechanism is related to an increase in energy expenditure that prevents fat accumulation in the body. These results have led us to propose that obesityassociated inflammation plays an important role in the regulation of energy metabolism. If the body loses the response to this activity of inflammation, the inflammation will not be able to promote energy expenditure, leading to an increased risk of obesity. We call this condition inflammation resistance, and we believe that it is required for the development of obesity.
Research in this laboratory is supported by grants from the National Institutes of Health and the American Diabetes Association.
For more information, visit our laboratory website: http://labs.pbrc.edu/generegulation