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The metabolic syndrome, in which cardiovascular disease and obesity play major roles, has become an important healthcare issue. Systemic concentrations of asymmetric dimethylarginine (ADMA) correlate with obesity and insulin resistance and it is considered to be an independent marker of cardiovascular disease. Currently, ADMA is understood to be an endogenous inhibitor of nitric oxide synthase; however, the direct effect of ADMA on adipocytes and in obesity has not been investigated. Here, we establish that ADMA in adipocytes regulates the expression and activity of the mTOR lipid synthesis pathway which results in adipocyte hypertrophy both in vitro and in vivo. Treatment of 3T3-L1 adipocytes with ADMA (10μM) resulted in adipocyte hypertrophy (control 27μm2 ±1.4, 10μM ADMA 33μm2± 1.6). This could not be mimicked through the blockade of NO by L-NAME (28μm2 ± 1.5) and PB-ITU (25μm2± 1.2). Hypertrophy was driven by an increase in mTOR expression (x2.4 ± 0.4) which upregulates ACC (x4.6 ± 0.8) and FASN (x1.4 ± 0.1) suggesting ADMA increases lipid production in an NO-independent manner. Investigations in vivo were explored through the genetic manipulation of DDAH1, an enzyme responsible for ADMA breakdown. Specific deletion of DDAH1 within adipocytes increased intracellular ADMA concentrations. This in turn caused an upregulation of mTOR, ACC and FASN expression and resulted in adipocyte hypertrophy. Conversely, genetic overexpression of DDAH1 reduced ADMA production within adipocytes and caused a down-regulation in mTOR expression. These data suggests that ADMA is a novel regulator of mTOR expression and activity at physiological concentrations. Pathological concentrations of ADMA are associated with adipocyte hypertrophy a known risk factor for insulin resistance and inflammation.