Lipoprotein lipase suppression in 3T3-L1 cells by an endotoxin-induced mediator from exudate cells.

Kawakami, Masanobu; Pekala, Phillip H.; Lane, M. Daniel; Cerami, Anthony

doi:10.1073/pnas.79.3.912

Cited by 227 publications

(82 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, it is also documented that TNF-␣ decreases the synthesis and activity of several proteins essential for lipogenesis and triglyceride accumulation in adipocytes. These include lipoprotein lipase (5,(7)(8)(9), acetyl-coenzyme A carboxylase (4,10,11), acyl-coenzyme A synthetase (12), stearoyl-coenzyme A desaturase (12), and the insulin-sensitive glucose transporter GLUT4 (13,14).…”

mentioning

confidence: 99%

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Hadri

Courtalon

Gauthereau

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

Modulation of ␤-adrenoreceptor expression by tumor necrosis factor-␣ (TNF-␣) was investigated in murine 3T3-F442A adipocytes. TNF-␣ treatment of mature adipocytes decreased ␤ 3 -adrenoreceptor mRNA content in a time-and concentration-dependent manner, with a 8.5-fold decrease observed after a 6-h exposure to 300 pM TNF-␣. ␤ 1 -Adrenoreceptor mRNA abundance was slightly decreased by TNF-␣ treatment, while ␤ 2 -adrenoreceptor mRNA levels were potently induced (6-fold increase at 6 h). (؊)-[ 125 I]Iodocyanopindolol saturation and competition binding experiments indicated that TNF-␣ induced a 2-fold decrease in ␤ 3 -adrenoreceptor number, a nonsignificant reduction in ␤ 1 -subtype population, and a ϳ4.5-fold increase in ␤ 2 -adrenoreceptor density. This correlated with a lower EC 50 value measured for epinephrine in stimulating adenylyl cyclase, whereas the EC 50 value for norepinephrine increased. Nuclear run-on assays on isolated nuclei and mRNA stability measurements showed that TNF-␣ increased both ␤ 2 -adrenoreceptor gene transcription and ␤ 2 -adrenoreceptor mRNA half-life, while ␤ 1 -and ␤ 3 -adrenoreceptor gene expression was modulated only at the transcriptional level by the cytokine. These findings demonstrate a differential modulation by TNF-␣ of the three ␤-adrenoreceptor subtypes in adipocytes, which may contribute to metabolic disorders induced by the cytokine in the adipocyte.Tumor necrosis factor-␣ (TNF-␣) 1 is a multifunctional cytokine that was originally identified as a tumoricidal protein (1). Subsequent investigations have shown that TNF-␣ was fundamentally involved in control of the growth, differentiation, and metabolism in several normal cells and tissues.A sum of work has been focused on the role of TNF-␣ in the regulation of adipocyte development and metabolism (1, 2). Thus, TNF-␣ strongly inhibits adipose conversion and even causes a dramatic dedifferentiation of adipocytes in culture (3-6). Moreover, it is also documented that TNF-␣ decreases the synthesis and activity of several proteins essential for lipogenesis and triglyceride accumulation in adipocytes. These include lipoprotein lipase (5, 7-9), acetyl-coenzyme A carboxylase (4, 10, 11), acyl-coenzyme A synthetase (12), stearoyl-coenzyme A desaturase (12), and the insulin-sensitive glucose transporter GLUT4 (13,14).In addition to the above effects on adipogenesis and reduction of de novo fatty acid synthesis, TNF-␣ also depletes triglycerides from adipocytes by directly increasing lipolysis (15-17). So far, the molecular mechanism by which the cytokine potentiates lipolysis remains unclear (17).Through activation of three ␤-AR subtypes, catecholamines exert a key role in the regulation of lipid metabolism in adipocytes. They modulate cAMP-dependent processes such as lipolysis and the genetic control of the lipogenic and thermogenic pathways. As regards the pleiotropic effects of TNF-␣ on several metabolic pathways in adipocytes, and to the key role of the ␤-AR system in lipid mobilization, it is possible that an interplay between TNF...

show abstract

mentioning

confidence: 99%

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Hadri

Courtalon

Gauthereau

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The observation of the correct relaxation time course and amplitude after the application of crude monocyte IL-1 is interesting in that context because LPS-stimulated monocytes also produce TNF-a and IL-6 (Kawakami et al, 1982;Ritchie et al, 1983). Classical bioassays of IL-1 based on thymocyte proliferation are prone to much interference from (Helle et al, 1988;Mizutani et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Human interleukin‐1 induces a rapid relaxation of the rabbit isolated mesenteric artery

Marceau

Petitclerc

deBlois

et al. 1991

British J Pharmacology

View full text Add to dashboard Cite

1 Strips of rabbit superior mesenteric artery, precontracted with phenylephrine, relaxed when exposed to human recombinant interleukin-1 (IL-1) of the a or fi types. The effect was observed within 10min, was optimal 32 min after the application of the cytokines and concentration-dependent (12-290 pM).2 IL-la and IL-1i were equipotent in relaxing the rabbit mesenteric artery. A synthetic fragment corresponding to [163][164][165][166][167][168][169][170][171] was approximately one million fold less active than IL-ifl. The tripeptide Lys-D-Pro-Thr, an analogue of was inactive as an antagonist of IL-1if on the preparation.3 Indomethacin (2.8pM) prevented or acutely reversed IL-1-induced relaxations in the rabbit mesenteric artery. Purified haemoglobin (10piM) or the removal of endothelium had no effect on relaxations elicited by IL-if,. 4 The preparation exhibited some selectivity for IL-1 as recombinant human tumour necrosis factor-a (TNF-a), IL-2 or IL-6 failed to influence it. TNF-a was not synergistic with a subthreshold concentration of IL-ifl. 5Immunoreactive 6-keto-prostaglandin Fl, and prostaglandin E2 were increased in the bathing fluid of isolated mesenteric arteries exposed to IL-if? as compared to controls. 6 A supernatant of lipopolysaccharide-stimulated human monocytes produced a relaxation of the preparation with a profile similar to that produced with IL-Is and there was a good quantitative agreement between the extent of the relaxation and the enzyme immunoassay measurements of IL-la and IL-1if in the supernatant. Furthermore the relaxation of crude monocyte IL-i was prevented by preincubating with antibodies to IL-la and IL-1if. This experiment illustrates the possible use of the preparation for bioassay of IL-1. 7 It is concluded that either form of IL-I relaxes the precontracted rabbit mesenteric artery by a prostaglandin-dependent, nitric oxide-independent mechanism. The model is also useful for distinguishing the mechanism of IL-1-induced hypotension in vivo in rabbits.

show abstract

“…Previous studies have shown that this hyperlipidemia, which is due to the accumulation of very low densitylipoproteins (VLDL) is the result of the loss of the enzyme lipoprotein lipase (3)(4)(5). We have recently demonstrated that the hyperlipidemia associated with endotoxemia is mediated by an endotoxin-induced macrophage product (4,5), which markedly suppresses the activity of lipoprotein lipase. In attempting to elucidate the biochemical mechanism by which this occurs we have utilized the 3T3-L1 murine preadipocyte cell line (6).…”

mentioning

confidence: 99%

“…The biochemical basis for this phenomenon is not understood, but presumably once triggered it is of a universal nature. In order to gain insight into the mechanism of this process, we have been studying as a model system the hyperlipidemia that occurs with infection or endotoxemia (3)(4)(5). Previous studies have shown that this hyperlipidemia, which is due to the accumulation of very low densitylipoproteins (VLDL) is the result of the loss of the enzyme lipoprotein lipase (3)(4)(5).…”

mentioning

confidence: 99%

“…In order to gain insight into the mechanism of this process, we have been studying as a model system the hyperlipidemia that occurs with infection or endotoxemia (3)(4)(5). Previous studies have shown that this hyperlipidemia, which is due to the accumulation of very low densitylipoproteins (VLDL) is the result of the loss of the enzyme lipoprotein lipase (3)(4)(5). We have recently demonstrated that the hyperlipidemia associated with endotoxemia is mediated by an endotoxin-induced macrophage product (4,5), which markedly suppresses the activity of lipoprotein lipase.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Selective inhibition of synthesis of enzymes for de novo fatty acid biosynthesis by an endotoxin-induced mediator from exudate cells.

Pekala¹,

Kawakami²,

Angus³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

125

View full text Add to dashboard Cite

An endotoxin-induced mediator from exudate cells markedly suppresses the activities of the key enzymes for de novo fatty acid biosynthesis-acetyl-CoA carboxylase [acetyl-CoA:carbon dioxide ligase (ADP-forming), EC 6.4.1.2] and fatty acid synthetase-in differentiating 3T3-L1 murine preadipocytes. The loss in activity, at least in part, appears to be due to a specific effect on the synthesis of the enzymes, as determined by a decreased incorporation of [mS] The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S.C. §1734 solely to indicate this fact.

show abstract

Lipoprotein lipase suppression in 3T3-L1 cells by an endotoxin-induced mediator from exudate cells.

Cited by 227 publications

References 28 publications

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Human interleukin‐1 induces a rapid relaxation of the rabbit isolated mesenteric artery

Selective inhibition of synthesis of enzymes for de novo fatty acid biosynthesis by an endotoxin-induced mediator from exudate cells.

Contact Info

Product

Resources

About