Over the past decades, a dramatic increase in accumulation of abdominal fat in the general population worldwide, and its consequences, has been observed. This has motivated researcher to further study its associated implications, not only in obesity. Currently, the impact of liver adiposity is well recognized, and liver disease of non-alcoholic origin can be considered as the hepatic manifestation of metabolic syndrome. The liver seems to have a central role in insulin signaling dependent on the availability of nutrients and other factors, in which intermediates such as hepatokines –mainly fetuin-A, a product present in inflammation and hepatic steatosis are involved,. Numerous tests are currently used for the diagnosis of insulin resistance, without this providing information about implication of other organs, or the relationship with abnormal fatty tissue. Similarly, no evidence that establishes a relationship between hepatokines and adipokines in the development of adiposopathy has been identified. In this publication we postulate that the relationship between liver and adipose tissue in the generation of insulin resistance can be explained by the alteration of the hepato-adiposity axis in a proinflammatory environment that favors the establishment of insulin disruption, thus contributing as a link that leads to adiposopathy and the associated comorbidities.