Interactions of Noradrenalin and Tumour Necrosis Factor Α, Interleukin 4 and Interleukin 6 in the Control of Lipolysis From Adipocytes Around Lymph Nodes

Mattacks, Christine A.; Pond, Caroline M.

doi:10.1006/cyto.1998.0442

Cited by 70 publications

(63 citation statements)

References 32 publications

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“…This fact may give a clue to the ontological development of leptin, a hormone with a cytokine structure having major effects on the hypothalamus but whose relation to inflammation appears to be somewhat peripheral. Pond, whose work is described elsewhere in the present symposium (Pond, 2001), has shown that there is a tight coupling of adipocyte metabolic activity with their distance to the nearest lymph node (Pond, 1999), and that TNF-α, and IL-4 and IL-6 may be part of this interaction (Mattacks & Pond, 1999). These facts demonstrate the linkage between adipose tissue and the immune system.…”

Section: Interactions Between Adipose Tissue Stores and Immunologymentioning

confidence: 79%

Pro-inflammatory cytokines and adipose tissue

2001

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Cytokines appear to be major regulators of adipose tissue metabolism. Therapeutic modulation of cytokine systems offers the possibility of major changes in adipose tissue behaviour. Cytokines within adipose tissue originate from adipocyte, preadipocyte and other cell types. mRNA expression studies show that adipocytes can synthesise both tumour necrosis factor a (TNF-a) and several interleukins (IL), notably IL-1b and IL-6. Other adipocyte products with ‘immunological’ actions include complement system products and macrophage colony-stimulating factor. Cytokine secretion within adipocytes appears similar to that of other cells. There is general agreement that circulating TNF-a and IL-6 concentrations are mildly elevated in obesity. Most studies suggest increased TNF-a mRNA expression or secretion in vitro in adipose tissue from obese subjects. The factors regulating cytokine release within adipose tissue appear to include usual ‘inflammatory‘ stimuli such as lipopolysaccaride, but also the size of the fat cells per se and catecholamines. There is conflicting data about whether insulin and cortisol regulate TNF-a. The effects of cytokines within adipose tissue include some actions that might be characterised as metabolic. TNF-a and IL-6 inhibit lipoprotein lipase, and TNF-a additionally stimulates hormone-sensitive lipase and induces uncoupling protein expression. TNF-a also down regulates insulin-stimulated glucose uptake via effects on glucose transporter 4, insulin receptor autophosphorylation and insulin receptor substrate-1. All these effects will tend to reduce lipid accumulation within adipose tissue. Other effects appear more ‘trophic’, and include the induction of apoptosis, regulation of cell size and induction of de-differentiation (the latter involving reduced peroxisome proliferator-activated receptor g). Cytokines are important stimulators and repressors of other cytokines. In addition, cytokines appear to modulate other regulatory systems. Examples of the latter include effects on leptin secretion (probably stimulation followed by inhibition) and reduction of b3-adrenoceptor expression. There seems to be no clear agreement as to which cytokines derived from adipose tissue act as remote regulators, i.e. hormones. Leptin, which is structurally a cytokine, is also a hormone. IL-6 appears to be released systemically by adipose tissue, but TNF-a is probably not. Both leptin and IL-6 appear to act on the hypothalamus, IL-6 acts on the liver, while leptin may have actions on the pancreas. The importance of the immune system in whole-body energy balance provides a rationale for the links between cytokines and adipose tissue. It seems clear that TNF-a is a powerful autocrine and paracrine regulator of adipose tissue. Other cytokines, notably leptin, and possibly IL-6, have lesser actions on adipose tissue. These cytokines act as hormones, reporting the state of adipose tissue stores throughout the body.

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Section: Interactions Between Adipose Tissue Stores and Immunologymentioning

confidence: 79%

Pro-inflammatory cytokines and adipose tissue

2001

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“…37 Both TNF-a and IL-6 applied alone stimulated lipolysis in perinodal adipocytes. 38 Intravenous injection of recombinant TNF-a to rats increased serum triacylglycerol, which was mainly due to an increased secretion of triacylglycerol by the liver. 39 Studies on adipocytes from mice lacking TNF receptor (TNFR) [TNFR1 (TNFR1(À/À)), TNFR2 (TNFR2(À/À)), or both (TNFR1(À/À) R2(À/À))] revealed that this effect was mediated mainly via TNFR1 40 and dependent on downregulation of lipid droplet-associated protein perilipin (PLIN).…”

Section: Tnf-a Induces Lipolysismentioning

confidence: 98%

TNF‐α, a potent lipid metabolism regulator

Chen

Xun

Chen³

et al. 2009

Cell Biochemistry & Function

193

120

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As a multifunctional cytokine, tumor necrosis factor alpha (TNF-a) exerts a series of biological actions in different cells, tissues, organs, and species and has been demonstrated to regulate and interfere with energy metabolism, especially lipid homeostasis. A large body of researches suggested that the effects of TNF-a on lipid metabolism mainly include five aspects: (1) suppresses free fatty acid (FFA) uptake and promotes lipogenesis; (2) induces lipolysis; (3) inhibits lipid-metabolism-related enzymes activity; (4) regulates cholesterol metabolism; (5) regulates other adipocyte-derived adipokines. The molecular mechanisms underlying these actions are complex and several signal transduction pathways might be involved. Regulation of metabolism-related gene expression at transcriptional and protein levels and impact on enzymes activity might be of importance. Identification and verification of these pathways might provide novel potential strategies and drug targets for dyslipidemia therapy. However, the inconsistent and even conflict conclusions on lipid profile drawn from human subjects after infliximab therapy poses the possibility that the effect of TNF-a on lipid metabolism might be more complicated than it appeared to be.

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“…IL-6 is secreted by adipose tissue at rest [12,13] and plasma IL-6 levels are elevated in insulin-resistant states [14,15]. IL-6 exerts lipolytic effects in adipocytes [16,17] and recombinant human (rh) IL-6 infusion increases adipose tissue lipolysis in healthy humans [18,19], resulting in increased plasma NEFA after prolonged (>2 h) infusion. Notably, the increased lipolysis occurs in the absence of changes in other hormones known to affect lipolysis [19].…”

Section: Introductionmentioning

confidence: 99%

Hormone-sensitive lipase is reduced in the adipose tissue of patients with type 2 diabetes mellitus: influence of IL-6 infusion

et al. 2004

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Aims/hypothesis: Type 2 diabetes mellitus is characterised by increased plasma NEFA and IL-6 concentrations, and IL-6 increases lipolysis in healthy men. We assessed the adipose tissue hormone-sensitive lipase (HSL) mRNA expression, protein expression and HSL activity in patients with type 2 diabetes mellitus, and determined the effect of IL-6 administration on these measures. Methods: Seven patients with type 2 diabetes mellitus (age 67±4 years, weight 87±7 kg) and six age-and weight-matched individuals visited the laboratory on two occasions. Subcutaneous adipose tissue biopsies and blood samples were obtained prior to and during 3 h of either saline or recombinant human IL-6 infusion. Results: HSL mRNA was reduced (p<0.05) by ∼40% in type 2 diabetes mellitus relative to control subjects, while HSL protein expression showed a tendency to be decreased (35%, p=0.09). HSL activity averaged 8.87±1.25 and 6.91±1.20 nmol min −1 mg −1 protein for control and type 2 diabetic subjects respectively (p<0.05). IL-6 administration increased (p<0.05) HSL mRNA 2-fold at 60 min in both groups, whereas HSL protein and activity were unaffected by IL-6. Plasma insulin was elevated (p<0.05) in patients with type 2 diabetes mellitus at rest and was blunted (p<0.05) during IL-6 infusion in both groups. Plasma glucagon and cortisol were elevated (p<0.05) by IL-6 in both groups. Conclusions/interpretation: Our data demonstrate that basal HSL is decreased in patients with type 2 diabetes mellitus, and this may be a consequence of elevated plasma insulin levels. We have also shown that IL-6 administration increases HSL gene expression, although it exerted no effect on HSL protein and activity. This disparity between mRNA, protein and enzyme activity may be a function either of the marked alterations in the hormonal milieu induced by IL-6 administration and/or of post-transcriptional events.

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Interactions of Noradrenalin and Tumour Necrosis Factor Α, Interleukin 4 and Interleukin 6 in the Control of Lipolysis From Adipocytes Around Lymph Nodes

Cited by 70 publications

References 32 publications

Pro-inflammatory cytokines and adipose tissue

Pro-inflammatory cytokines and adipose tissue

TNF‐α, a potent lipid metabolism regulator

Hormone-sensitive lipase is reduced in the adipose tissue of patients with type 2 diabetes mellitus: influence of IL-6 infusion

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