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Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia.

Sarraf P, Frederich RC, Turner EM, Ma G, Jaskowiak NT, Rivet DJ, Flier JS, Lowell BB, Fraker DL, Alexander HR - J. Exp. Med. (1997)

Bottom Line: Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions.IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels.After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased.

View Article: PubMed Central - PubMed

Affiliation: Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

ABSTRACT
Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions. In C57BL/6 female mice, the administration of TNF, IL-1, and, to a lesser extent, leukemia inhibitory factor (LIF), produced a prompt and dose-dependent increase in serum leptin levels and leptin mRNA expression in fat. IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels. After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased. These findings suggest that leptin levels may be one mechanism by which anorexia is induced during acute inflammatory conditions.

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Effect of LPS on ob  gene expression. After a 7-h fast  mice were injected i.p. with LPS  at the doses indicated and adipose tissue harvested 5 h later as  described. ob gene expression is  low in fasted animals treated  with PBS and increased in a  dose-dependent manner after LPS.
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Figure 3: Effect of LPS on ob gene expression. After a 7-h fast mice were injected i.p. with LPS at the doses indicated and adipose tissue harvested 5 h later as described. ob gene expression is low in fasted animals treated with PBS and increased in a dose-dependent manner after LPS.

Mentions: After a 7-h evening fast, mice were treated with a single intraperitoneal injection of LPS, or multiple cytokines at doses that have an anorectic effect (Ma, G. and H.R. Alexander, manuscript in preparation). Fig. 2 shows that leptin levels are significantly increased by LPS, TNF, IL-1, and LIF in a doserelated manner. LPS and TNF increased leptin levels nearly five fold to levels greater than that seen in animals acutely fasted and refed. IL-1 and LIF increased fasting leptin by approximately twofold, a level similar to that observed in fed animals. IL-6 had a trend to increase leptin, which did not reach significance. LPS administration at sublethal (1 and 10 mg/kg) and lethal doses (20 and 30 mg/kg) produced a dose-dependent increase in ob gene expression in fasted mice (Fig. 3). In this model, 20–30 mg/kg of LPS resulted in a 30–40% lethality by 72 h after adminstration (data not shown). These effects were specific, because IL-10 and IL-4, which generally exhibit anti-inflammatory characteristics, as well as IL-2 and ciliary neurotrophic factor (CNTF), had no effect on leptin mRNA expression in retroperitoneal fat (data not shown) or serum leptin levels (see Fig. 2).


Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia.

Sarraf P, Frederich RC, Turner EM, Ma G, Jaskowiak NT, Rivet DJ, Flier JS, Lowell BB, Fraker DL, Alexander HR - J. Exp. Med. (1997)

Effect of LPS on ob  gene expression. After a 7-h fast  mice were injected i.p. with LPS  at the doses indicated and adipose tissue harvested 5 h later as  described. ob gene expression is  low in fasted animals treated  with PBS and increased in a  dose-dependent manner after LPS.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196098&req=5

Figure 3: Effect of LPS on ob gene expression. After a 7-h fast mice were injected i.p. with LPS at the doses indicated and adipose tissue harvested 5 h later as described. ob gene expression is low in fasted animals treated with PBS and increased in a dose-dependent manner after LPS.
Mentions: After a 7-h evening fast, mice were treated with a single intraperitoneal injection of LPS, or multiple cytokines at doses that have an anorectic effect (Ma, G. and H.R. Alexander, manuscript in preparation). Fig. 2 shows that leptin levels are significantly increased by LPS, TNF, IL-1, and LIF in a doserelated manner. LPS and TNF increased leptin levels nearly five fold to levels greater than that seen in animals acutely fasted and refed. IL-1 and LIF increased fasting leptin by approximately twofold, a level similar to that observed in fed animals. IL-6 had a trend to increase leptin, which did not reach significance. LPS administration at sublethal (1 and 10 mg/kg) and lethal doses (20 and 30 mg/kg) produced a dose-dependent increase in ob gene expression in fasted mice (Fig. 3). In this model, 20–30 mg/kg of LPS resulted in a 30–40% lethality by 72 h after adminstration (data not shown). These effects were specific, because IL-10 and IL-4, which generally exhibit anti-inflammatory characteristics, as well as IL-2 and ciliary neurotrophic factor (CNTF), had no effect on leptin mRNA expression in retroperitoneal fat (data not shown) or serum leptin levels (see Fig. 2).

Bottom Line: Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions.IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels.After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased.

View Article: PubMed Central - PubMed

Affiliation: Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

ABSTRACT
Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions. In C57BL/6 female mice, the administration of TNF, IL-1, and, to a lesser extent, leukemia inhibitory factor (LIF), produced a prompt and dose-dependent increase in serum leptin levels and leptin mRNA expression in fat. IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels. After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased. These findings suggest that leptin levels may be one mechanism by which anorexia is induced during acute inflammatory conditions.

Show MeSH
Related in: MedlinePlus