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.
2013
Curtin WM, Menegus MA, Patru MM, Peterson CJ, Metlay LA, Mooney RA, Stanwood NL, Scheible AL, Dorgan A. "Midtrimester fetal herpes simplex-2 diagnosis by serology, culture and quantitative polymerase chain reaction." Fetal diagnosis and therapy. 2013 33(2):133-6. Epub 2012 Oct 11. |
2012 Nov 23
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. 2012 Nov 23; Epub 2012 Nov 23. |
2012 Feb
Barry CT, Mills B, Hah Z, Mooney RA, Ryan CK, Rubens DJ, Parker KJ. "Shear wave dispersion measures liver steatosis." Ultrasound in medicine & biology. 2012 Feb 0; 38(2):175-82. Epub 2011 Dec 16. |
2011 Nov
Clementi AH, Gaudy AM, Zimmers TA, Koniaris LG, Mooney RA. "Deletion of interleukin-6 improves pyruvate tolerance without altering hepatic insulin signaling in the leptin receptor-deficient mouse." Metabolism: clinical and experimental. 2011 Nov 0; 60(11):1610-9. Epub 2011 May 31. |
2011 Sep 21
Sampson ER, Hilton MJ, Tian Y, Chen D, Schwarz EM, Mooney RA, Bukata SV, O'Keefe RJ, Awad H, Puzas JE, Rosier RN, Zuscik MJ. "Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis." Science translational medicine. 2011 Sep 21; 3(101):101ra93. |
