Adipose tussue and homocysteine metabolism

Homocysteine (Hcy) is a non-protein aminoacid which is an intermediate of methionine metabolism. Elevated homocysteine level (hyperhomocysteinemia) is a risk factor of cardiovascular diseases. In addition, obesity and metabolic syndrome are associated with greater prevalence of atherosclerosis. The purpose of this article is to discuss the relationship between adipose tissue and Hcy metabolism. All enzymes involved in the synthesis and metabolism of Hcy are expressed in adipose tissue, and recent studies suggest that adipose tissue may be an important source of circulating homocysteine. The effect of obesity on Hcy level is controversial, however, most experimental and clinical studies indicate that Hcy is elevated in the metabolic syndrome in the absence of diabetes. Homocysteine elevation in the metabolic syndrome may result from either hyperinsulinemia or the impairment of renal function. In contrast, plasma Hcy is reduced in both type 1 and type 2 diabetes if renal function is normal, but becomes elevated when diabetic nephropathy develops. Leptin, which is markedly elevated in obese patients, has no effect on total plasma Hcy, but increases the level of homocysteine thiolactone - a cyclic thioester of homocysteine which plays an important role in complications of hyperhomocysteinemia. The effect of leptin is accounted for by the inhibition of paraoxonase 1 (PON1) - the HDL-associated esterase, which hydrolyzes homocysteine thiolactone to Hcy. In addition, recent studies indicate that homocysteine may induce insulin resistance in adipose tissue by promoting endoplasmic reticulum stress and/or disrupting adipokine production; e.g. enhancing resistin and suppressing adiponectin. Biomedical Reviews 2009; 20: 7-15.