Leukemia inhibitory factor induces changes in lipid metabolism in cultured adipocytes.

Abstract

Cytokines induce a number of changes in lipid metabolism that can produce hyperlipidemia. Leukemia inhibitory factor (LIF), a recently discovered cytokine, has been suggested to play a role in the cancer cachexia syndrome through its ability to decrease lipoprotein lipase (LPL) activity. This study explores the mechanism by which LIP decreases LPL activity in cultured adipocytes and determines its effects on fatty acid synthesis and lipolysis to see if it shares the same catabolic effects on fat cells as seen with other cytokines, such as tumor necrosis factor (TNF). LIF decreased LPL activity in cultured adipocytes by 44% compared with an 85% decrease produced by TNF. Although the percent decrease in LPL activity is not as great in LIF-incubated adipocytes as in TNF-incubated adipocytes, the half-maximal doses for both cytokines are similar. LPL messenger RNA levels paralleled LPL activity in the LIF-treated adipocytes, suggesting that the effect of LIF on LPL activity is predominantly mediated through transcriptional regulation. In contrast to TNF, LIF tended to increase the de novo synthesis of fatty acids. Acetyl coenzyme-A carboxylase messenger RNA levels paralleled the changes seen in fatty acid synthesis for both cytokines. LIF caused a small increase in lipolysis, whereas TNF increased lipolysis by greater than 2-fold. These results demonstrate that the catabolic effects of LIF are weaker than those of TNF and are predominantly directed toward decreasing LPL activity, which may contribute to the hyperlipidemia associated with infection, inflammation, and cancer.

Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases

“…Several studies have described lipolytic actions in adipocytes for IL-6 ( 45 ) and other members of the gp130 ligand family of cytokines such as leukemia inhibitory factor ( 46 ). However, differential effects have been found among cytokines of this family.…”

Molecular analysis of lipid‐depleting factor in a colon‐26‐inoculated cancer cachexia model

“…In vitro studies revealed that LIF caused a small increase in lipolysis but tended to increase de novo synthesis of fatty acids in 3T3-L1 cells. 53 Lipolytic activity of IFN-␥ or IL-1 has been described on fully differentiated adipocytes. 19,49,54 Todorov et al 55,56 purified a lipid-mobilizing factor from a cachexia-inducing murine tumor (MAC16) and from the urine of patients with cancer cachexia.…”

Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters.

“…LPS, TNF, IL-1, the interferons, and leukemia inhibitor factor decrease the activity of lipoprotein lipase, decrease de novo fatty acid synthesis, and increase lipolysis in adipose cells (4,(33)(34)(35). Many of these effects are due to regulation of adipose tissue mRNA.…”