Fever responses of Zucker rats with and without fatty mutation of the leptin receptor.
Leptin is thought to be involved in febrigenic signaling from the periphery to the brain. Zucker obese rats have a so-called fatty mutation in the leptin receptor gene and express a dysfunctional protein. Studies comparing the fever responses of fatty (fa/fa) rats and of their lean (Fa/Fa and Fa/fa) counterparts yield contradictory results. To resolve these contradictions, we evaluated the effect of fatty mutation on infectious and stress-associated fevers at thermoneutrality (29 degrees C) and in a cool environment (20 degrees C). Zucker fa/fa and Fa/? rats were infused with Escherichia coli lipopolysaccharide (LPS; 10 microg/kg) through a jugular catheter (infectious fever) or with saline through the catheter (control) or received a painful intramuscular injection of saline (stress fever). At thermoneutrality, the colonic temperature (T(c)) responses of fatty rats to all stimuli tested were no different from the responses of lean rats. In a cool environment, T(c) responses of fatty rats to all stimuli were ~0.5 degrees C lower than those of lean rats. The observed attenuation of LPS-induced and stress-associated fevers in Zucker fatty rats in the cold agrees with the literature data showing that brown adipose tissue (the major heat production effector) is morphologically and functionally defective in these rats. The normal febrile responses of fatty Zucker rats to pyrogenic stimuli at thermoneutrality indicate that fatty mutation does not interrupt febrigenic signaling from the periphery to the brain.
Ivanov
Andrei I
AI
Trauma Research, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA.
Romanovsky
Andrej A
AA
D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics*; D003080:Cold Temperature; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology*; D008070:Lipopolysaccharides; D008297:Male; D009154:Mutation / Q000502:physiology; D009765:Obesity / Q000503:physiopathology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012965:Sodium Chloride; D013312:Stress, Physiological / Q000503:physiopathology
D002352:Carrier Proteins; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012965:Sodium Chloride