Research Interests:

Major Research Interests:

1. Traumatic injury in obesity: Traumatic injury is a leading cause of death of individual under 44 years old in United States. Traumatic injury is associated with severe inflammatory responses and multiple organs failure (MOF). Obesity is increasing at an alarming rate in the United States. O ne of the key observations in obese subjects is the recognition of a state of chronic inflammation. Increasing evidence shows that c ritically injured obese trauma patients exhibit higher risk of MOF and mortality rates associated with exaggerated inflammatory responses as compared to nonobese trauma patients. Consistent with previous finings in obesity, our preliminary study shows increased numbers of monocyte/macrophage along with elevated inflammatory markers in obese Zucker rats (OZR), a model of metabolic syndrome. The enhanced inflammation in obesity is induced, at least in part, by insulin resistance and resultant metabolic disorders. Hyperglycemia in the first week following trauma is associated higher mortality in patients. More than 90% of patients with severe trauma suffer long bone fractures and usually an acute postinjury surgery such as external fixation with intramedullary nail (IMN) is recommended. However, local surgery, especially in obesity, has shown to increase the systemic inflammation. Therefore, surgery immediately following trauma in obesity may exaggerate the inflammatory response and increase the chance of MOF and mortality.

2. Adipocyte Derived Relaxing Factors in mediating the functional hyperemic response: Obese individuals exhibit a blunted increase in blood flow in response to exercise (functional hyperemia), which prevents patients from a dequate exercise, a useful therapy for weight control, metabolic disorders and cardiovascular diseases. W e have demonstrated that in obese Zucker rats (OZR), a model of obesity, the basal arteriolar tone is similar with their lean controls (LZR) whereas the functional vasodilation is attenuated due to impaired K ATP channel function. However, this appears to be different in different models of obesity since we found a loss of arteriolar tone due to a basal activation of K ATP channels in other obese animal models, such like ob-/ob- mice (ob), MC4R-/- mice and high fat diet induced obese (DIO) rat or mice. Recent studies have suggested that local adipose tissue release vasodilator(s), termed adipocyte-derived relaxing factors (ADFs), can cause endothelial dysfunction and relaxation of vascular smooth muscle. Although the nature of ADFs is unclear, it has been suggested that ADFs induce vasorelaxation by opening potassium channels including ATP-sensitive potassium channels (K ATP). We have shown that K ATP channels in arteriolar smooth muscle cells are inactivated under basal conditions and the activation of K ATP channels is important for the functional vasodilatory response. Therefore, any activation of K ATP channels induced by ADFs may attenuate the functional vasodilation through the loss of this vasodilatory pathway. In preliminary experiments we collected subcutaneous fat (SF) from ob, MC4R-/-, and DIO mice and incubated the fat in PSS. In all cases the SF-conditioned PSS induced a significantly loss of arteriolar tone in the lean controls which was almost completely inhibited by K ATP channel inhibition. These results suggest that ADFs are released from adipose tissue in most obese models. In future studies we will determine the nature of ADFs and how they impaired functional hyperemic response to exercise in obesity.