title: Involvement of sympathetic nervous system and brown fat in endotoxin-induced fever in rats.
abstract: The object of this study was to assess the role of brown adipose tissue (BAT) and the sympathetic nervous system in the rise in heat production associated with endotoxin-induced fever. Oxygen consumption (VO2) was found to be significantly increased (28%) over a 4-h period after two doses of endotoxin (Escherichia coli lipopolysaccharide, 0.3 mg/100 g body wt) given 24 h apart. Injection of a mixed beta-adrenoceptor antagonist (propranolol) reduced VO2 by 14% in endotoxin-treated rats, whereas the selective beta 1- (atenolol) or beta 2- (ICI 118551) antagonists suppressed VO2 by 10%. These drugs did not affect VO2 in control animals. BAT thermogenic activity assessed from measurements of in vitro mitochondrial guanosine 5'-diphosphate (GDP) binding was elevated by 54% in interscapular BAT and by 171% in other BAT depots. Surgical denervation of one lobe of the interscapular depot prevented these responses. Endotoxin failed to stimulate GDP binding in rats fed protein-deficient diets. This may have been because BAT thermogenic activity was already elevated in control rats fed these diets or because endotoxin caused a marked suppression of food intake in the protein-deficient animals. The results indicate that sympathetic activation of BAT is involved in the thermogenic responses to endotoxin and that these can be modified by dietary manipulation.
authors.affiliation: Nutrition Research Unit, London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: M M
authors.initials: MM
authors.lastname: Jepson
authors.forename: D J
authors.initials: DJ
authors.lastname: Millward
authors.forename: N J
authors.initials: NJ
authors.lastname: Rothwell
authors.forename: M J
authors.initials: MJ
authors.lastname: Stock
mesh_terms: D002001:Adipose Tissue, Brown / Q000502:physiology*; D000818:Animals; D004044:Dietary Proteins / Q000008:administration & dosage; D004731:Endotoxins; D004926:Escherichia coli; D005334:Fever / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D004044:Dietary Proteins; D004731:Endotoxins