Interleukin-15 mediates reciprocal regulation of adipose and muscle mass: a potential role in body weight control

Carbó, Neus; López‐Soriano, Joaquín; Costelli, Paola; Álvarez, Belén; Busquets, Sı́lvia; Baccino, Francesco M.; Quinn, LeBris S.; López‐Soriano, Francisco J.; Argilés, Josep Μ.

doi:10.1016/s0304-4165(00)00188-4

Cited by 157 publications

(155 citation statements)

References 38 publications

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“…This protective effect was also noticeable in terms of wet tissue weight for the skeletal muscles (Table 2). In agreement with previous observations (Carbó et al, 2000), IL-15 did not exert any trophic action (weight or protein increase) on muscles in non-tumour bearers (Tables 2 and 3).…”

Section: Resultssupporting

confidence: 93%

“…The lack of effect of IL-15 on adipose tissue in AH-130 hosts may thus reflect the fact that lipid mobilization was already occurring in these animals and could not easily be stimulated further. When the cytokine treatment was applied to control rats, however, adipose tissue mass decreased with respect to untreated controls (by 34%), in agreement with previous reports (Carbó et al, 2000).…”

Section: Discussionsupporting

confidence: 92%

“…Another important action of IL-15 is to reduce the body fat content by inhibiting lipogenesis (Carbó et al, 2000); tissuespecific modulations in lipoprotein lipase activity could provide an additional mechanism for promoting a decreased lipid accretion in adipose tissue. The present cachexia model is itself characterized by extensive lipid mobilization (Dessì et al, 1992;Carbó et al, 1994), associated with decreased activity of tissue lipoprotein lipase (Carbó et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

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Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats

et al. 2000

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Tissue protein hypercatabolism (TPH) is an important feature in cancer cachexia, particularly with regard to the skeletal muscle. The Yoshida AH-130 rat ascites hepatoma is a model system for studying the mechanisms involved in the processes that lead to tissue depletion, since it induces in the host a rapid and progressive muscle wasting, primarily due to TPH. The present study was aimed at investigating if IL-15, which is known to favour muscle fibre hypertrophy, could antagonize the enhanced muscle protein breakdown in this cancer cachexia model. Indeed, IL-15 treatment partly inhibited skeletal muscle wasting in AH-130-bearing rats by decreasing (8-fold) protein degradative rates (as measured by 14 C-bicarbonate pre-loading of muscle proteins) to values even lower than those observed in non-tumour-bearing animals. These alterations in protein breakdown rates were associated with an inhibition of the ATP-ubiquitin-dependent proteolytic pathway (35% and 41% for 2.4 and 1.2 kb ubiquitin mRNA, and 57% for the C8 proteasome subunit, respectively). The cytokine did not modify the plasma levels of corticosterone and insulin in the tumour hosts. The present data give new insights into the mechanisms by which IL-15 exerts its preventive effect on muscle protein wasting and seem to warrant the implementation of experimental protocols involving the use of the cytokine in the treatment of pathological states characterized by TPH, particularly in skeletal muscle, such as in the present model of cancer cachexia. © 2000 Cancer Research Campaign

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Section: Resultssupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats

et al. 2000

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“…In connection to lipid metabolism, in the course of in vivo studies regarding the effects of IL15 on skeletal muscle, a 33% decrease in WAT mass was observed in rats, with no changes in food intake (15). In another study using obese rodent models, a correlation was found between the sensitivity to the fatinhibiting effects of IL15 and the fat expression of mRNA for key signaling subunits of the IL15 receptor in WAT (16), suggesting that IL15 may have a direct effect on this tissue.…”

Section: Introductionmentioning

confidence: 99%

PPARδ mediates IL15 metabolic actions in myotubes: Effects of hyperthermia

Fuster

Busquets

Figueras³

et al. 2009

Int J Mol Med

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Abstract. C2C12 cells exposed to hyperthermia (41˚C) experienced an increase in both protein synthesis and degradation. The addition of IL15 under hyperthermic conditions resulted in an important increase in protein synthesis with no changes in protein degradation, except when cells overexpressed PPAR‰. The PPAR‰ agonist GW501516 exerted similar effects on protein synthesis to IL15. Expression of a mutant dominant negative form of PPAR‰ prevented the effect of the cytokine on protein synthesis, suggesting that this transcription factor is involved in the anabolic action of IL15. The present study also suggests that the effects of IL15 on lipid oxidation could be mediated by PPAR‰.

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“…We previously demonstrated that this cytokine can act as an autocrine anabolic factor for skeletal muscle (15). 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.…”

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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Interleukin-15 mediates reciprocal regulation of adipose and muscle mass: a potential role in body weight control

Cited by 157 publications

References 38 publications

Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats

Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats

PPARδ mediates IL15 metabolic actions in myotubes: Effects of hyperthermia

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

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