Leptin produces anorexia and weight loss without inducing an acute phase response or protein wasting.
The ob gene product leptin is known to produce anorexia and loss of body fat when chronically administered to both lean and genetically obese mice. The current study was undertaken to examine whether administration of recombinant leptin in quantities sufficient to produce decreases in food intake and body weight and alterations in body composition would elicit either an hepatic acute phase protein response or preferential loss of carcass lean tissue. Mice were administered increasing quantities of recombinant human leptin or human tumor necrosis factor-alpha as a positive control. Although leptin (at 10 mg/kg body wt) produced significant anorexia and weight loss (both P < 0.05), human leptin administration did not appear to induce an hepatic acute phase protein response in either lean or genetically obese mice, as determined by protein synthetic rates in the liver or changes in the plasma concentration of the murine acute phase protein reactants, amyloid A, amyloid P, or seromucoid (alpha1-acid glycoprotein). In addition, human leptin administration did not induce a loss of fat-free dry mass (protein) in lean or obese animals. The findings suggest that at doses adequate to alter food intake and body weight leptin is not a significant inducer of the hepatic acute phase response nor does leptin promote the preferential loss of somatic protein characteristic of a chronic inflammatory process.
Kaibara
A
A
Department of Surgery, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
Moshyedi
A
A
Auffenberg
T
T
Abouhamze
A
A
Copeland
E M
EM
Kalra
S
S
Moldawer
L L
LL
D000210:Acute-Phase Reaction / Q000139:chemically induced*; D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D001835:Body Weight / Q000187:drug effects*; D002100:Cachexia / Q000139:chemically induced*; D005260:Female; D006801:Humans; D020738:Leptin; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000494:pharmacology*; D013997:Time Factors
D020738:Leptin; D011506:Proteins