title: High-fat diet induces increased tissue expression of TNF-alpha.
abstract: In several strains of genetically obese and insulin resistant rodents, adipose tissue over expresses mRNA for tumor necrosis factor alpha (TNF-alpha). Our purpose was to determine whether tissue expression of TNF-alpha protein is elevated in rats that are made obese and insulin resistant by administration of a high-fat diet. Young Wistar rats weighing approximately 50 g were fed for 39 days with either normal rat chow (12.4% fat) or a high-fat diet (50% fat). After 33 days, glucose tolerance was assessed and after 39 days, insulin-stimulated transport of [3H]-2-deoxyglucose was assessed in isolated strips of soleus muscle. Rats on the high-fat diet consumed slightly fewer calories but became obese, displaying significant approximately 2-fold increases in the mass of both visceral and subcutaneous fat depots. High-fat feeding also caused a moderate degree of insulin resistance. Fasting serum insulin was significantly increased, as were insulin and glucose concentrations following glucose loading. In isolated strips of soleus muscle, the high-fat diet produced a trend toward a 33% decrease in the insulin-stimulated component of glucose transport (p=0.064). Western analysis of muscle, liver and fat revealed two forms of TNF-alpha, a soluble 17 Kd form (sTNF-alpha) and a 26 Kd membrane form (mTNF-alpha). Both sTNF-alpha and mTNF-alpha were relatively abundant in fat; whereas sTNF-alpha was the predominant form present in muscle and liver. High-fat feeding caused a significant 2-fold increase in muscle sTNF-alpha, along with a trend toward a 54% increase in visceral fat sTNF-alpha (p=0.055). TNF-alpha was undetectable in serum. We conclude that muscle over expression of TNF-alpha occurs during the development of diet-induced obesity and may, in part cause insulin resistance by an autocrine mechanism.
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32608-1197, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Borst
authors.forename: Christine F
authors.initials: CF
authors.lastname: Conover
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D003847:Deoxyglucose / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D003847:Deoxyglucose