Introduction Resistin is a novel cysteine rich peptide hormone encoded at the RSTN gene secreted by the adipocyte. Since its discovery it has proposed link with obesity related insulin re- sistance and type 2 diabetes 1 . It is unclear whether resistin production is increased 1,2 or decreased in obesity 3 . Expression of resistin levels have been reported to be decreased in white adipose tissue of several animal models of obesity 3,4 . Additionally, Way et al reported that administration of PPAR-gamma ligands actually increased resistin expression in both obese mice and Zucker diabetic fatty rats 3 . The physiologic role of resistin in humans remains unknown. Recently, it is suggested that circulating resistin levels are not associat- ed with obesity or insulin resistance in hu- mans 5,6 . However, these are cross-sectional studies and effects of weight loss were not studied. In order to better understand the physiologic role of resistin in human obesity, we measured the serum resistin concentra- tions in patients with severe obesity to test the hypothesis that serum resistin concentrations are elevated amongst individuals with severe obesity (defined as BMI > 35 kg/m 2 ), and weight loss would reduce these levels. Recent- ly we have published our findings of effects of weight loss 7 in patients with severe obesity by using either low carbohydrate or low fat diets. Here we are presenting our data on serum re- sistin levels in obese individuals before and after 6-months of dietary intervention. European Review for Medical and Pharmacological Sciences 161 Abstract. – Background: Resistin has proposed link with obesity related insulin resis- tance and type 2 diabetes. The physiologic role of resistin in humans remains unknown. It is suggested that circulating resistin levels are not associated with obesity or insulin resistance in humans. However, the effects of weight loss on serum resistin concentration has not been stud- ied. In order to better understand the physiolog- ic role of resistin in human obesity, we mea- sured the serum resistin concentration in sub- jects with severe obesity (before and after 6- months of dietary intervention) to test the hy- pothesis that serum resistin concentrations are elevated amongst individuals with severe obesi- ty and weight loss would reduce these levels. Methods: Seventy-one obese subjects (de- fined as BMI > 35 kg/m 2 ) who were randomized to low fat (LF) vs low carbohydrates (LC) diets and who completed the 6-month follow-up were studied. Their baseline demographic information was collected and serum resistin, insulin, glu- cose were measured at baseline and at 6- months. Results: Subjects in LC diet lost more weight than LF (-19.54 ± 7.87 lbs vs -7.83 ± 11.23 lbs., p = 0.001). Insulin sensitivity (HOMA) improved in LC group compared with LF group [-3.72 ± 9.84 (LC) vs +1.31 ± 7.31 (LF), p = 0.006]. Serum re- sistin levels did not decrease in either diet. Conclusions: Our study found that despite a significant weight loss and improvement in in- sulin sensitivity there was no reduction in serum resistin concentration in morbidly obese men with metabolic syndrome suggesting that re- sistin does not play a central role in obesity re- lated insulin resistance. Key Words: Obesity, Resistin, Weight loss, Diet, Insulin. 2005; 9: 161-165 Serum resistin is not associated with obesity or insulin resistance in humans N. IQBAL 1,2 , P. SESHADRI 1,2 , L. STERN 1 , J. LOH 2 , S. KUNDU 3 , T. JAFAR 4 , F.F. SAMAHA 5 1 Department of Medicine, Section of Endocrinology Diabetes and Metabolism, Philadelphia VA Medical Center, Philadelphia, Pennsylvania (USA) 2 Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (USA) 3 Department of Medicine, Pennsylvania Hospital, Philadelphia, PA (USA) 4 Department of Medicine, Section of Nephrology, Aga Khan University, Karachi (Pakistan) 5 Department of Medicine, Section of Cardiology, Philadelphia, VA Medical Center, Philadelphia, Pennsylvania (USA)