Leptin Expression Is Reduced with Acute Endotoxemia in the Pig: Correlation with Glucose, Insulin, and Insulin-like Growth Factor-1 (IGF-1)

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Abstract
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 (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.