Search

Leptin has been implicated in the regulation of anorexia associated with cachexia in rodents and humans. Regulation of leptin expression is under complex endocrine and metabolic control. To determine if leptin expression is regulated by acute inflammation and to define the endocrine and metabolic factor(s) that regulates leptin expression during acute inflammation, castrate male pigs (ad libitum fed, used as their own controls) were treated with saline (control period) and endotoxin (lipopolysaccharide [LPS] period). Frequent blood samples were collected to identify dynamic changes in hormones and metabolites that are known to regulate leptin expression. LPS caused fever and elevated plasma cortisol (p < 0.0004), tumor necrosis factor-alpha (TNF-alpha) (p < 0.0001), and plasma nonesterified fatty acids (NEFA) (p < 0.001) compared with control. Circulating insulin (p < 0.01), glucose (p < 0.003), and insulin-like growth factor-1 (IGF-1) (p < 0.0001), as well as adipose leptin mRNA abundance (p < 0.01), were profoundly reduced following LPS treatment compared with control. Our data indicate that during acute endotoxemia (1-10 h after injection), leptin gene expression is decreased compared with ad libitum fed animals and is more closely related to energy homeostasis than cytokine profiles in plasma.

The physiologic response to infection includes reductions in tissue concentrations of anabolic growth factors as a means of reducing growth and conserving nutrients for immunologic processes. This repartitioning of nutrients is accompanied by anorexia, which has been linked to increased leptin expression. Furthermore, leptin and growth hormone (GH) concentrations are inversely related, with leptin being required for normal GH release. The objective of this study was to determine if pretreatment with GH would influence endotoxin-induced changes in leptin expression or attenuate endotoxin-induced reductions in serum insulin-like growth factor-1 (IGF-1) and IGF-1 expression in liver and longissimus muscle. In experiment 1, 40 pigs were assigned to four treatments (n = 10 per treatment) arranged as a 2x2 factorial with GH (s.c. injection, 2 mg 1 h before challenge and 2 mg 2 h after challenge) and endotoxin (single i.m. injection, 25 microg/kg body weight) as main effect variables. Pretreatment with GH resulted in a marked increase (p<0.001) in serum GH within 1 h that was sustained throughout the study. Endotoxin challenge reduced (p<0.003) serum IGF-1 independent of GH (GH x endotoxin, p>0.682), and reduced (p<0.05) IGF-1 expression in longissimus muscle but not liver. Leptin mRNA abundance was reduced 56% (p<0.005) by GH but was not affected by endotoxin (p>0.81). In experiment 2, 36 pigs (n = 12 per treatment) were either allowed ad libitum feed consumption with no injection or deprived of feed and injected twice with either saline or endotoxin 24 h apart. Feed deprivation reduced leptin expression (p<0.05). However, endotoxin did not change leptin expression but markedly increased (p<0.05) serum haptoglobin. These data indicate that changes in IGF-1 status in endotoxin-challenged pigs are independent of serum GH and that leptin expression is not increased by endotoxin challenge in the pig. These data also indicate a regulatory linkage between GH and leptin in vivo.