The liver is the key organ for the development of metabolic syndrome.

The metabolic syndrome affects more than a third of the US and Mexican populations, predisposing to the development of some metabolic disorders.1,2 In fact, it is well recognized that subjects with generalized obesity suffer from a high risk of insulin resistance and its metabolic complications, such as type 2 diabetes mellitus, hypertriglyceridemia, low levels of high density lipoprotein cholesterol, hypertension, hepatic steatosis, hyperuricemia, and atherosclerotic vascular disease.3 Insulin resistance has long been considered to have a central role in the development of a range of metabolic disorders. Some of the links between components of the metabolic syndrome relate to insulin resistance, although about 30% of patients with the metabolic syndrome have normal insulin sensitivity. 4 Insulin resistance is characterized by high plasma insulin concentration that fails to suppress plasma glucose normally. Under normal conditions, insulin regulates uptake, oxidation, and storage of fuel within insulinsensitive tissues—liver, skeletal muscle, and adipose tissue. Insulin affects energy regulation via intracellular signalling cascades that originate at the insulin receptor. Binding of insulin to its receptor stimulates autophosphorylation of tyrosine residues that act as docking sites for ‘downstream’ signaling molecules; the latter include the janus-activated kinases (JAK) and insulin receptor substrates (IRS)-1 and IRS-2. Several disease processes alter the operation of these signalling pathways.5 What is not clear is the time course of the development of insulin resistance. It appears that hepatic insulin resistance may be the primary defect. Recent reports point to that effect.