Research
My team studies the molecular and physiological pathways involved in the regulation of human appetite and body weight and their disruption in obesity. Some of the molecular pathways involved in regulating weight also regulate blood pressure and lipid metabolism, and affect an individual's risk of cardiovascular diseases.
One of the links between obesity and cardiovascular disease is leptin. We have identified mutations in leptin gene using candidate gene approach in patients with severe, early onset obesity, and have demonstrated that leptin contributes to hypertension in obese individuals. These results suggest that pharmacological approaches that modulate leptin’s effects on cells could represent a useful therapeutic strategy for the treatment of obesity-associated hypertension and might help prevent a subset of obesity-associated cardiovascular disease.
Publications
Leptin mediates the increase in blood pressure associated with obesity. Simonds SE, Pryor JT, Ravussin E, Greenway FL, Dileone R, Allen AM, Bassi J, Elmquist JK, Keogh JM, Henning E, Myers MG Jr, Licinio J, Brown RD, Enriori PJ, O'Rahilly S, Sternson SM, Grove KL, Spanswick DC, Farooqi IS, Cowley MA. Cell. 2014 Dec 4;159(6):1404-16.
20 years of leptin: human disorders of leptin action. Farooqi IS, O'Rahilly S. J Endocrinol. 2014 Oct;223(1):T63-70.
Obesity-associated melanocortin-4 receptor mutations are associated with changes in the brain response to food cues. van der Klaauw AA, von dem Hagen EA, Keogh JM, Henning E, O'Rahilly S, Lawrence AD, Calder AJ, Farooqi IS. J Clin Endocrinol Metab. 2014 Oct;99(10):E2101-6.
Functional characterization of obesity-associated variants involving the α and β isoforms of human SH2B1. Pearce LR, Joe R, Doche ME, Su HW, Keogh JM, Henning E, Argetsinger LS, Bochukova EG, Cline JM, Garg S, Saeed S, Shoelson S, O'Rahilly S, Barroso I, Rui L, Farooqi IS, Carter-Su C. Endocrinology. 2014 Sep;155(9):3219-26.
KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation. Pearce LR, Atanassova N, Banton MC, Bottomley B, van der Klaauw AA, Revelli JP, Hendricks A, Keogh JM, Henning E, Doree D, Jeter-Jones S, Garg S, Bochukova EG, Bounds R, Ashford S, Gayton E, Hindmarsh PC, Shield JP, Crowne E, Barford D, Wareham NJ; UK10K consortium, O'Rahilly S, Murphy MP, Powell DR, Barroso I, Farooqi IS. Cell. 2013 Nov 7;155(4):765-77.
Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Azizan EA, Poulsen H, Tuluc P, Zhou J, Clausen MV, Lieb A, Maniero C, Garg S, Bochukova EG, Zhao W, Shaikh LH, Brighton CA, Teo AE, Davenport AP, Dekkers T, Tops B, Küsters B, Ceral J, Yeo GS, Neogi SG, McFarlane I, Rosenfeld N, Marass F, Hadfield J, Margas W, Chaggar K, Solar M, Deinum J, Dolphin AC, Farooqi IS, Striessnig J, Nissen P, Brown MJ. Nat Genet. 2013 Sep;45(9):1055-60.
Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Asai M, Ramachandrappa S, Joachim M, Shen Y, Zhang R, Nuthalapati N, Ramanathan V, Strochlic DE, Ferket P, Linhart K, Ho C, Novoselova TV, Garg S, Ridderstråle M, Marcus C, Hirschhorn JN, Keogh JM, O'Rahilly S, Chan LF, Clark AJ, Farooqi IS, Majzoub JA. Science. 2013 Jul 19;341(6143):275-8.
