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Sihem Boudina

Associate Professor of Nutrition and Integrative Physiology and Adjunct Associate Professor of Biochemistry, Adjunct Associate Professor of Internal Medicine, and Adjunct Assistant Professor Surgery

Director of the Metabolic Phenotyping Core Facility

Obesity, Oxidative Stress, Insulin Resistance, Autophagy, Adipose Progenitors

Boudina Photo


Molecular Biology Program


B.S. University of Science and Technology, Algeria

M.S. University of Bordeaux 2, France

Ph.D. University of Bordeaux 2, France



The prevalence of obesity has increased in the United States and in most of the Westernized World over recent decades, reaching worldwide epidemics. Since obesity worsens most of the cardiovascular disease (CVD) risk factors, most CVD, including hypertension, coronary heart disease, heart failure, and atrial fibrillation, are all increased in the setting of obesity. My laboratory is dedicated to understanding the molecular mechanisms controlling the formation and the expansion of visceral obesity and to deciphering its role in the pathogenesis of CVD.

Redox-Regulation of Adipocyte Function
Oxidative stress (OS) occurs when reactive oxygen species (ROS) production exceeds their rate of detoxification in the cell, which promotes damage to various biomolecules such as nucleic acids, lipids and proteins. Obesity is one of multiple conditions associated with OS. In addition to increased systemic biomarkers of OS, obese humans and animals exhibit increased adipose tissue OS as evidenced by higher hydrogen peroxide (H2O2) production, reduced antioxidant defense mechanisms, enhanced adenine dinucleotide phosphate (NADPH) oxidase activity and elevated oxidative damage to proteins. While the link between OS and obesity has been established, the causal role for mitochondrial ROS in fat accumulation in vivo is not known. We utilized mouse models of gain and loss of function of major antioxidant defense systems in adipocytes to investigate the mechanisms underlying redox-regulation of adipocytes function.

Regulation of Visceral Adipose Tissue Mass in Health and Disease
Visceral (VIS) obesity is a predictor of adverse metabolic and cardiovascular outcomes independently of body mass index (BMI). VIS obesity is associated with the development of cardiometabolic abnormalities such as insulin resistance, glucose intolerance, type 2 diabetes, atherogenic dyslipidemia, inflammation, altered cytokine profile, impaired fibrinolysis, increased risk of thrombosis and endothelial dysfunction. White adipose tissue (WAT) expansion occurs by adipocyte hypertrophy or by de novo recruitment and differentiation of adipose progenitors (hyperplasia). The hypertrophic growth of VIS adipose tissue has been involved in the genesis of unhealthy obesity that is associated with altered systemic metabolism and increased cardiovascular risk. Research in our lab is aimed to provide mechanistic insights into the development of hypertrophic VIS obesity through the functional characterization of novel VIS adipose progenitors (APs).


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Insulin Resistance and Cardiac Dysfunction
Heart disease is the major cause of morbidity and mortality in patients with diabetes, with the incidence of cardiovascular disease in diabetic patients being twice that of non-diabetic men and three times that of non-diabetic women. More than two-thirds of diabetic patients die from cardiovascular complications including diabetic cardiomyopathy and heart failure but the underlying mechanisms remain poorly understood. Although diabetic cardiomyopathy is caused by both type 1 and type 2 diabetes, the latest accounts for 90% of diabetic patients worldwide and is characterized by the combination of inadequate insulin secretion and insulin resistance. Several mechanisms have been proposed to mediate diabetic cardiac injury including altered metabolism and mitochondrial dysfunction, enhanced oxidative stress, impaired calcium signaling and altered autophagy. Our research is focused on understanding the signaling pathways downstream of the insulin and the IGF-1 receptors that regulate autophagy and to examine the functional consequences of altered autophagy in the heart.


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  1. Han YH, Buffolo M, Pires KM, Pei S, Scherer PE, Boudina S. Adipocyte-Specific Deletion of Manganese Superoxide Dismutase Protects from Diet-Induced Obesity Via Increased Mitochondrial Uncoupling and Biogenesis. Diabetes. 2016 PMID: 27284109
  2. Boudina S, Graham TE. Mitochondrial function/dysfunction in white adipose tissue. Exp Physiol. 2014 Sep;99(9):1168-78. PMID: 25128326.
  3. Silva FJ, Holt DJ, Vargas V, Yockman J, Boudina S, Atkinson D, Grainger DW, Revelo MP, Sherman W, Bull DA, Patel AN. Metabolically active human brown adipose tissue derived stem cells. Stem Cells. 2014 Feb;32(2):572-81. PMID: 24420906.
  4. Pires KM, Ilkun O, Valente M, Boudina S. Treatment with a SOD mimetic reduces visceral adiposity, adipocyte death, and adipose tissue inflammation in high fat-fed mice. Obesity (Silver Spring). 2014 Jan;22(1):178-87. PMCID: PMC3758415.
  5. Fullmer TM, Pei S, Zhu Y, Sloan C, Manzanares R, Henrie B, Pires KM, Cox JE, Abel ED, Boudina S. Insulin suppresses ischemic preconditioning-mediated cardioprotection through Akt-dependent mechanisms. J Mol Cell Cardiol. 2013 Nov;64:20-9. PMCID: PMC3835741.
  6. lkun O, Boudina S. Cardiac dysfunction and oxidative stress in the metabolic syndrome: an update on antioxidant therapies. Curr Pharm Des. 2013;19(27):4806-17. Review. PMCID: PMC3856187.
  7. Dodson MV, Boudina S, Albrecht E, Bucci L, Culver MF, Wei S, Bergen WG, Amaral AJ, Moustaid-Moussa N, Poulos S, Hausman GJ. A long journey to effective obesity treatments: is there light at the end of the tunnel? Exp Biol Med (Maywood). 2013 May;238(5):491-501. PMID: 23856900.
  8. Boudina S. Cardiac aging and insulin resistance: could insulin/insulin-like growth factor (IGF) signaling be used as a therapeutic target? Curr Pharm Des. 2013;19(32):5684-94. Review. PMCID: PMC3883087.
  9. Boudina S, Han YH, Pei S, Tidwell TJ, Henrie B, Tuinei J, Olsen C, Sena S, Abel ED. UCP3 regulates cardiac efficiency and mitochondrial coupling in high fat-fed mice but not in leptin-deficient mice. Diabetes. 2012 Dec;61(12):3260-9. PMCID: PMC3501860.
  10. Bricker DK, Taylor EB, Schell JC, Orsak T, Boutron A, Chen YC, Cox JE, Cardon CM, Van Vranken JG, Dephoure N, Redin C, Boudina S, Gygi SP, Brivet M, Thummel CS, Rutter J. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science. 2012 Jul 6;337(6090):96-100. PMCID: PMC3690818.
  11. Boudina S, Sena S, Sloan C, Tebbi A, Han YH, O’Neill BT, Cooksey RC, Jones D, Holland WL, McClain DA, Abel ED. Early mitochondrial adaptations in skeletal muscle to diet-induced obesity are strain dependent and determine oxidative stress and energy expenditure but not insulin sensitivity. Endocrinology. 2012 Jun;153(6):2677-88. PMCID: PMC3359615.
  12. Li Y, Wende AR, Nunthakungwan O, Huang Y, Hu E, Jin H, Boudina S, Abel ED, Jalili T. Cytosolic, but not mitochondrial, oxidative stress is a likely contributor to cardiac hypertrophy resulting from cardiac specific GLUT4 deletion in mice. FEBS J. 2012 Feb;279(4):599-611. PMCID: PMC3267000.
  13. Bugger H, Riehle C, Jaishy B, Wende AR, Tuinei J, Chen D, Soto J, Pires KM, Boudina S, Theobald HA, Luptak I, Wayment B, Wang X, Litwin SE, Weimer BC, Abel ED. Genetic loss of insulin receptors worsens cardiac efficiency in diabetes. J Mol Cell Cardiol. 2012 May;52(5):1019-26. PMCID: PMC3327790.
  14. Ishiwata T, Orosz A, Wang X, Mustafi SB, Pratt GW, Christians ES, Boudina S, Abel ED, Benjamin IJ. HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice. PLoS One. 2012;7(8):e42118. PMCID: PMC3411653.
Last Updated: 7/19/21