Research Bio
Obesity is increasing at an alarming rate in the industrialized world. This is a serious health concern because there is a strong association between obesity and insulin resistance, type 2 diabetes, hypertension, cancer, and cardiovascular disease. Our lab is particularly interested in the link between obesity and type 2 diabetes. Type 2 diabetes currently afflicts 6-7% of the U.S. population. It is characterized by defective insulin action (insulin resistance) leading to poor control of blood glucose (sugar) levels. The disease can lead to heart disease, blindness, kidney failure, amputations, and nerve damage. Sedentary lifestyle and poor eating habits leading to obesity are contributing to the increased incidence of diabetes at all ages.
It has now become apparent that obesity-dependent insulin resistance and type 2 diabetes have characteristics of a chronic inflammatory state. This link between inflammation and insulin resistance is the focus of our lab. In one area of our work, we are testing the hypothesis that cytokines (particularly interleukin-6) contribute to inhibition of insulin receptor signaling in target tissues leading to insulin resistance. Consistent with this model, IL-6 levels are 2-3 times higher in the blood of diabetics than controls. We have demonstrated that a family of regulatory proteins, SOCS (Suppressors of Cytokine Signaling) proteins, are induced by IL-6 and other inflammatory cytokines in liver cells. SOCS proteins appear to bind to the components of the insulin receptor signaling pathway and inhibit insulin action. Thus, we propose the inflammatory environment of obesity increases expression of SOCS3 leading to insulin resistance. We are currently testing this model of obesity-dependent insulin resistance at the cellular level and with experimental animals.
The obese, type 2 diabetic has twice the risk of osteoarthritis when compared to a non-obese, non-diabetic individual. The traditional explanation for this risk is the increased bio-mechanical stress on the joint as a consequence of increased body weight. In another area of our lab's research, we have proposed an alternate explanation that attributes at least some of the progression of osteoarthritis in this population to metabolic dysregulation and chronic inflammation that is a hallmark of obesity-mediated diabetes. Recent investigations in our lab using diet-induced obese mice have provided experimental evidence to support a metabolic component to accelerated osteoarthritis progression in obesity-mediated diabetes. Ongoing investigations with genetic and dietary mouse models as well as in vitro models are being employed to define the metabolic pathways that are involved. Therapeutic modalities are also being investigated.
2014 Apr
Barry CT, Hah Z, Partin A, Mooney RA, Chuang KH, Augustine A, Almudevar A, Cao W, Rubens DJ, Parker KJ. "Mouse liver dispersion for the diagnosis of early-stage Fatty liver disease: a 70-sample study." Ultrasound in medicine & biology. 2014 Apr; 40(4):704-13. Epub 2014 Jan 10. |
2014
David MA, Jones KH, Inzana JA, Zuscik MJ, Awad HA, Mooney RA. "Tendon repair is compromised in a high fat diet-induced mouse model of obesity and type 2 diabetes." PloS one. 2014 9(3):e91234. Epub 2014 Mar 21. |
2014
Brown ML, Yukata K, Farnsworth CW, Chen DG, Awad H, Hilton MJ, O'Keefe RJ, Xing L, Mooney RA, Zuscik MJ. "Delayed fracture healing and increased callus adiposity in a C57BL/6J murine model of obesity-associated type 2 diabetes mellitus." PloS one. 2014 9(6):e99656. Epub 2014 Jun 09. |
2013 Nov
Shi J, Liang Q, Wang Y, Mooney R, Boyce B, Xing L. "Use of a whole-slide imaging system to assess the presence and alteration of lymphatic vessels in joint sections of arthritic mice." Biotechnic & histochemistry : official publication of the Biological Stain Commission. 2013 Nov; 88(8):428-39. Epub 2012 Nov 23. |
2013 Nov
Inzana JA, Kung M, Shu L, Hamada D, Xing LP, Zuscik MJ, Awad HA, Mooney RA. "Immature mice are more susceptible to the detrimental effects of high fat diet on cancellous bone in the distal femur." Bone. 2013 Nov; 57(1):174-83. Epub 2013 Aug 14. |
