Rajagopal V. Sekhar, M.D.
Associate Professor of Medicine
One Baylor Plaza, Room R604 (MS: BCM185)
Houston, TX 77030
- Medical School: St. John's National Academy of Health Sciences, Bangalore, India, 1990
- Internship: St. John's National Academy of Health Sciences Hospital, India, 1991-92
- Research: Nutrition and Metabolism Research Institute, St. John's National Academy of Health Sciences, Bangalore, India, 1993-94
- Internal Medicine Residency: India 1992-93; United Kingdom 1995-98; United States 2001-03
- Clinical Fellowship (Diabetes, Endocrinology and Metabolism): 1998-2000, Baylor College of Medicine, Houston TX
- Research Fellowship (Metabolism): 2000-01, Baylor College of Medicine and USDA/ARS Children's Nutrition Research Center, Houston, TX
My lab is focused on understanding how abnormalities in the metabolism of fat, protein and glucose leads to defects in fuel and energy metabolism, and how this results in insulin resistance, obesity and dyslipidemia in diabetes, HIV associated lipodystrophy and aging. Our research approach is translational and begins at the bedside in human studies, and is complemented by rodent models in the lab, where we identify mechanisms and test interventions at the whole-body, cellular and mitochondrial levels, before returning to the bedside for human studies. Our methods include stable isotope protocols in humans and rodents, gas chromatograph mass spectrometry (GCMS), liquid chromatography (HPLC and MS), rodent and human calorimetry, and mitochondrial respiration studies. Our focus is on:
- Glutathione kinetics in aging and diabetes: we studied and found elderly humans and humans with poorly controlled diabetes to have severe deficiency of glutathione (GSH, a vital endogenous antioxidant protein). Further we found GSH deficiency to occur due to decreased synthesis of GSH, and associated with increased oxidative stress and oxidant damage. Short-term dietary supplementation with GSH precursor amino-acids completely restored GSH synthesis and significantly lowered oxidative stress and oxidant damage. We are now investigating the links between GSH, diabetic microvascular complications and abnormal fuel metabolism in mouse models of aging and diabetes, and translating this to human studies and therapy. These studies are expected to identify novel approaches to treat diabetic complications and insulin resistance.
- HIV associated lipodystrophy: this is a unique phenotype of patients with abnormal lipid kinetics including increased lipolytic rates and impaired fatty-acid oxidation. Our focus is on investigating novel mechanisms underlying increased risk of heart disease and dyslipidemia in HIV associated lipodystrophy.
- Obesity: we are studying abnormalities in fat metabolism to understand novel mechanisms contributing to obesity and diabesity.
- Growth hormone deficiency (GHD): we are studying how GHD affects protein, fat and glucose metabolism, and effects of GH replacement at physiological doses.
- Sekhar RV, McKay SV, Patel SG, Guthikonda AP, Reddy VT, Balasubramanyam A, Jahoor F. Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diab Care 2011 Jan;34(1):162-7. PMID: 20929994
- Balasubramanyam A, Coraza I, Smith EO, Scott LW, Patel P, Iyer D, Taylor AA, Giordano TP, Sekhar RV, Clark P, Cuevas-Sanchez E, Kamble S, Ballantyne CM, Pownall HJ. Combination of niacin and fenofibrate with lifestyle changes improves dyslipidemia and hypoadiponectinemia in HIV patients on antiretroviral therapy: results of "heart positive," a randomized, controlled trial. J Clin Endocrinol Metab. 2011 Jul;96(7):2236-47. PMID: 21565796
- Sekhar RV, Patel SG, Guthikonda AP, Reid M, Balasubramanyam A, Taffet GE, Jahoor F. Deficient synthesis of glutathione plays a key role in aging-related oxidative stress, and can be corrected by dietary cysteine and glycine supplementation Am J Clin Nutr. 2011; Sep;94(3):847-53. PMID: 21795440
- Sekhar RV, Patel SG, D’Amico S, Shi J, Balasubramanyam A, Rehman A, Jahoor F, Visnegarwala F. Effects of rosiglitazone on abnormal lipid kinetics in HIV associated dyslipidemic lipodystrophy: a stable isotope study. Metabolism Sep 9, 2010. PMID: 20832829
- Sekhar RV, Balasubramanyam A. Treatment of dyslipidemia in HIV-infected patients. Expert Opin Pharmacother. 2010 Aug;11(11):1845-54. PMID: 20486828
- Balasubramanyam A, Rao S, Misra R, Sekhar RV, Ballantyne CM. Prevalence of metabolic syndrome and associated risk factors in Asian Indians. J Immigr Minor Health. 2008 Aug;10(4):313-23. PMID: 18026838