Antioxidant and Gene Regulation Laboratory


  • Jianping Ye, M.D.


Our 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.


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. 

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