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.
2016 Sep 2
Wexler O, Gough MS, Morgan MA, Mack CM, Apostolakos MJ, Doolin KP, Mooney RA, Arning E, Bottiglieri T, Pietropaoli AP. "Methionine Metabolites in Patients With Sepsis." Journal of intensive care medicine. 2016 Sep 2; Epub 2016 Sep 02. |
2016 Jun
Hamada D, Maynard R, Schott E, Drinkwater CJ, Ketz JP, Kates SL, Jonason JH, Hilton MJ, Zuscik MJ, Mooney RA. "Suppressive Effects of Insulin on Tumor Necrosis Factor-Dependent Early Osteoarthritic Changes Associated With Obesity and Type 2 Diabetes Mellitus." Arthritis & rheumatology. 2016 Jun; 68(6):1392-402. |
2015 Oct
Beier EE, Inzana JA, Sheu TJ, Shu L, Puzas JE, Mooney RA. "Effects of Combined Exposure to Lead and High-Fat Diet on Bone Quality in Juvenile Male Mice." Environmental health perspectives. 2015 Oct; 123(10):935-43. Epub 2015 Apr 10. |
2015 Jun
Farnsworth CW, Shehatou CT, Maynard R, Nishitani K, Kates SL, Zuscik MJ, Schwarz EM, Daiss JL, Mooney RA. "A humoral immune defect distinguishes the response to Staphylococcus aureus infections in mice with obesity and type 2 diabetes from that in mice with type 1 diabetes." Infection and immunity. 2015 Jun; 83(6):2264-74. Epub 2015 Mar 23. |
2015 Jun
Barry CT, Hazard C, Hah Z, Cheng G, Partin A, Mooney RA, Chuang KH, Cao W, Rubens DJ, Parker KJ. "Shear wave dispersion in lean versus steatotic rat livers." Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2015 Jun; 34(6):1123-9. |
