Effects of interleukin-15 (IL-15) on adipose tissue mass in rodent obesity models: evidence for direct IL-15 action on adipose tissue

Álvarez, Belén; Carbó, Neus; López‐Soriano, Joaquín; Drivdahl, Rolf H.; Busquets, Sı́lvia; López‐Soriano, Francisco J.; Argilés, Josep Μ.; Quinn, LeBris S.

doi:10.1016/s0304-4165(02)00148-4

Cited by 93 publications

(69 citation statements)

References 21 publications

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“…147880) maps to chromosome 1q21 in a region of replicated linkage to type 2 diabetes (11,12). The common genetic variants in IL-6R have been identified recently, and a more general pattern of linkage disequilibrium of these variant needs to be established (380).…”

Section: B the Genes Encoding Il-6 And The Il-6 Receptormentioning

confidence: 99%

Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6

Pedersen¹,

Febbraio²

2008

Physiological Reviews

1,791

1,646

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Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as “myokines.” Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.

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Section: B the Genes Encoding Il-6 And The Il-6 Receptormentioning

confidence: 99%

Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6

Pedersen¹,

Febbraio²

2008

Physiological Reviews

1,791

1,646

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“…16,17 In addition, there is important reciprocal regulation between adipose tissue and skeletal muscle; one example is myocyte-secreted IL-6 and IL-15, which play a critical role in regulating adipose tissue function. 18,19 Given the fact that hepatocytes overproduce a variety of metabolites, including homocysteine following prolonged alcohol exposure, we postulated that alcohol-induced overproduction of homocysteine represented such a pathway and played a role in the inhibition of adiponectin expression and secretion in ALD. We conducted both in vivo and in vitro experiments to test our hypothesis.…”

mentioning

confidence: 99%

Inhibition of adiponectin production by homocysteine: A potential mechanism for alcoholic liver disease

Song¹,

Zhou²,

Deaciuc³

et al. 2007

Hepatology

114

125

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Although recent evidence suggests that down-regulation of production of the adipocyte hormone adiponectin has pathophysiological consequences for the development of alcoholic liver disease (ALD), the underlying mechanisms are elusive. Abnormal hepatic methionine-homocysteine metabolism induced by prolonged alcohol exposure has been reported both in clinical and experimental studies of ALD. Here, we conducted both in vivo and in vitro experiments to examine the effects of prolonged alcohol exposure on homocysteine levels in adipose tissue, its potential involvement in regulating adiponectin production, and the consequences for ALD. Chronic alcohol exposure decreased the circulating adiponectin concentration and adiponectin messenger RNA (mRNA) and protein levels in epididymal fat pads. Alcohol feeding induced modest hyperhomocysteinemia and increased homocysteine levels in the epididymal fat pad, which was associated with decreased mRNA levels of cystationine ␤-synthase. Betaine supplementation (1.5%, wt/vol) in the alcohol-fed mice reduced homocysteine accumulation in adipose tissue and improved adiponectin levels. Moreover, exogenous homocysteine administration reduced gene expression, protein levels, and secretion of adiponectin in primary adipocytes. Furthermore, rats fed a high-methionine diet (2%, wt/wt) were hyperhomocysteinemic and had decreased adiponectin levels in both plasma and adipose tissue, which was associated with suppressed AMP-activated protein kinase activation in the liver. Mechanistic studies revealed that both inactivation of the extracellular signal regulated kinase 1/2 pathway and induction of endoplasmic reticulum stress response, specifically C/EBP homologous protein expression, may contribute to the inhibitory effect exerted by homocysteine. Conclusion: Chronic alcohol feeding caused abnormal accumulation of homocysteine in adipocytes, which contributes to decreased adiponectin production in ALD. (HEPATOLOGY 2008;47:867-879.)

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“…Interestingly, in the course of in vivo studies, it was observed that IL-15 treatment causes an important reduction in WAT mass, parallel to the effects on protein metabolism (16). These effects seem to be direct in adipose tissue (17), and are partially mediated by a lower uptake of triacylglycerols (16) and a reduction of lipogenesis (21). Additionally, it was mentioned that indirect mechanisms by which lipid deposition in WAT could be affected, like a decrease on intestinal lipid absorption (22) and changes in liver lipogenic rate, leading to lipoproteins with a lower content in triacylglycerols.…”

Section: Intracellular Camentioning

confidence: 99%

“…In the course of in vivo studies regarding the effects of IL-15 on skeletal muscle, a 33% decrease in white adipose tissue (WAT) mass was observed in rats, with no changes in food intake (15,16). In another study using obese rodent models, a correlation was found between the sensitivity to the fat-inhibiting effects of IL-15 and the mRNA expression of key signalling subunits of the IL-15 receptor in WAT (17), suggesting that IL-15 has a direct effect on this tissue. Additionally, Quinn et al (18) reported a direct inhibition of adipogenesis in 3T3-L1 cells, which is linked to a decrease in PPARÁ2, confirming the direct action of the cytokine on WAT.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-15 increases calcineurin expression in 3T3-L1 cells: Possible involvement on in vivo adipocyte differentiation

Almendro

Fuster²,

Ametller³

et al. 2009

Int J Mol Med

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Abstract. Different studies have revealed that the Ca 2+ -dependent serine/threonine phosphatase calcineurin is involved in the regulation of adipocyte differentiation. Calcineurin acts as a Ca 2+ -dependent molecular switch that negatively regulates the ability of 3T3-L1 cells to undergo adipocyte differentiation by preventing the expression of critical proadipogenic transcription factors. In this study we investigated the role of interleukin-15 (IL-15), a cytokine previously known to be involved in the control of fat accretion by adipose cells, in the differentiation of the 3T3-L1 preadipose cell line. We found that IL-15 is able to increase ·-calcineurin mRNA content in white adipose tissue of rats chronically treated with the cytokine and also in the 3T3-L1 preadipose cell line. Moreover, IL-15 promoted a decrease in both leptin mRNA expression and lipid accumulation, as estimated by Red Oil O staining. Cotreatment with IL-15 and FK506 (a calcineurin inhibitor) resulted in no changes in lipid content compared with the non-treated group. These data suggest that IL-15 directly inhibits adipogenesis, possibly by upregulating ·-calcineurin and preventing the induction of adipocyte differentiation.

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Effects of interleukin-15 (IL-15) on adipose tissue mass in rodent obesity models: evidence for direct IL-15 action on adipose tissue

Cited by 93 publications

References 21 publications

Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6

Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6

Inhibition of adiponectin production by homocysteine: A potential mechanism for alcoholic liver disease

Interleukin-15 increases calcineurin expression in 3T3-L1 cells: Possible involvement on in vivo adipocyte differentiation

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