Stephen O’Rahilly

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Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many expression quantitative trait locus (eQTL) studies, typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a(More)
The close correspondence between energy intake and expenditure over prolonged time periods, coupled with an apparent protection of the level of body adiposity in the face of perturbations of energy balance, has led to the idea that body fatness is regulated via mechanisms that control intake and energy expenditure. Two models have dominated the discussion(More)
Peroxisome proliferator-activated receptor-γ co-activator-1α (PPARGC1A) is a transcriptional co-activator with a central role in energy expenditure and glucose metabolism. Several studies have suggested that the common PPARGC1A polymorphism Gly482Ser may be associated with risk of type 2 diabetes, with conflicting results. To clarify the role of Gly482Ser(More)
Stearoyl-CoA desaturase (SCD) is emerging as a key regulator of lipid and carbohydrate metabolism. Scd-null mice display a beneficial metabolic phenotype characterised by resistance to obesity, diabetes and hyperlipidaemia. The human homologue, SCD, maps to a region of chromosome 10 linked to type 2 diabetes, and SCD activity correlates with insulin(More)
*Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge, U.K., †Cardiovascular and Gastrointestinal Discovery Research Department, AstraZeneca Pharmaceuticals, Macclesfield, U.K., ‡MRC Dunn Human Nutrition Unit, Cambridge, U.K., and §Departments of(More)
OBJECTIVE Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macrophage (ATM) polarization, in the(More)
Obesity is associated with increased blood pressure (BP), which in turn increases the risk of cardiovascular diseases. We found that the increase in leptin levels seen in diet-induced obesity (DIO) drives an increase in BP in rodents, an effect that was not seen in animals deficient in leptin or leptin receptors (LepR). Furthermore, humans with(More)
To the Editor: Dunnigan-Köbberling syndrome or familial partial lipodystrophy (FPL) is an inherited form of partial lipodystrophy characterised by selective loss of subcutaneous limb and gluteal fat, and excess facial fat deposition [1]. Some authors have suggested that FPL be subclassified into Dunnigan and Köbberling subtypes [2], the key difference being(More)
Recent studies suggest that wingless-type MMTV integration site family, member 10B (WNT10B) may play a role in the negative regulation of adipocyte differentiation in vitro and in vivo. In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene. We(More)