In the obese adipose tissue produces proinflammatory molecules as tumor necrosis factor-alpha, which has local effects on adipocyte physiology and systemic effects in other organs. Many studies linking TNF-alpha, obesity, insulin resistance and lipid metabolism have been conducted in rats, rabbits and dogs, but the results observed in several of these studies have been conflicting and many of them have not been able to reproduce in humans, which on human makes difficult the interpretation of the effect of TNF-alpha on human metabolism. Objective: To conduct a systematic review of human studies which relates, TNF-alpha insulin resistance and lipoprotein metabolism. Methods: We searched the PubMed database for studies in humans, human tissue and human cell lines linking TNF-alpha, obesity, insulin resistance and lipoprotein. Results: There is a increased production of TNF-alpha on adipose tissue of obese. TNF-alpha decreases the cellular response to insulin in adipocytes, hepatocytes and human muscle cells. There is an increase of TNF-alpha in patients with dyslipidemia, and inactivation of TNF-alpha affects lipid metabolism. In human hepatocytes, TNF-alpha inhibits expression of APO AI, which may decrease the secretion of high density lipoproteins. TNF-alpha affects the excretion of cholesterol by inhibiting the enzyme cholesterol-7 alpha-hydroxylase in hepatocytes. Conclusion: TNF-alpha decreases the cellular response to insulin, and has effects on the metabolism of cholesterol and lipoproteins in humans. A better understanding of the mechanisms of the inflammatory response induced obesity in humans, can lead to identifying new therapeutic targets that can prevent the complications associated with obesity. (Nutr Hosp. 2012;27:1751-1757) DOI:10.3305/nh.2012.27.6.6004