The role of interleukin 1β in the anti-adipogenic action of macrophages on human preadipocytes

Gagnon, AnneMarie; Foster, Charlie; Landry, Anne; Sorisky, Alexander

doi:10.1530/joe-12-0565

Cited by 35 publications

(19 citation statements)

References 36 publications

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“…Thus, as has been shown recently, insulin-dependent induction of CCL2 (MCP-1) could be an early step in the recruitment of additional inflammatory cells into the expanded adipose tissue (24). IL-1␤ released from macrophages has been envisaged as major factor causing insulin resistance in adipocytes (2) and is a strong inhibitor of adipocyte differentiation (8). An insulin-induced production of IL-1␤ might thus contribute to the unfavorable phenotype of adipose tissue with large lipid-overloaded and insulinresistant adipocytes found in obese patients.…”

Section: Discussionmentioning

confidence: 88%

Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes

Manowsky

Camargo

Kipp

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Manowsky J, Camargo RG, Kipp AP, Henkel J, Püschel GP. Insulininduced cytokine production in macrophages causes insulin resistance in hepatocytes. Am J Physiol Endocrinol Metab 310: E938-E946, 2016. First published April 19, 2016 doi:10.1152/ajpendo.00427.2015.-Overweight and obesity are associated with hyperinsulinemia, insulin resistance, and a low-grade inflammation. Although hyperinsulinemia is generally thought to result from an attempt of the ␤-cell to compensate for insulin resistance, there is evidence that hyperinsulinaemia itself may contribute to the development of insulin resistance and possibly the low-grade inflammation. To test this hypothesis, U937 macrophages were exposed to insulin. In these cells, insulin induced expression of the proinflammatory cytokines IL-1␤, IL-8, CCL2, and OSM. The insulin-elicited induction of IL-1␤ was independent of the presence of endotoxin and most likely mediated by an insulin-dependent activation of NF-B. Supernatants of the insulin-treated U937 macrophages rendered primary cultures of rat hepatocytes insulin resistant; they attenuated the insulin-dependent induction of glucokinase by 50%. The cytokines contained in the supernatants of insulin-treated U937 macrophages activated ERK1/2 and IKK␤, resulting in an inhibitory serine phosphorylation of the insulin receptor substrate. In addition, STAT3 was activated and SOCS3 induced, further contributing to the interruption of the insulin receptor signal chain in hepatocytes. These results indicate that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues. metabolic syndrome; type 2 diabetes; inflammation; macrophage; insulin; cytokines DESPITE TREMENDOUS EFFORTS to raise public awareness about potential health hazards, the prevalence of overweight and obesity continues to increase (22). Concurrently, the incidence of impaired glucose tolerance, insulin resistance, and the often ensuing type 2 diabetes is rising at a stunning rate. Several molecular mechanisms have been proposed to explain the development of insulin resistance in obese patients. Thus, accrual of lipids with second-messenger properties in the course of ectopic triglyceride accumulation, namely diacylglycerol, can activate protein kinases, e.g., protein kinase C. This may result in the interruption of the intracellular insulin receptor signal chain by an inhibitory serine phosphorylation of the first relay protein in this chain, the insulin receptor sub-

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Section: Discussionmentioning

confidence: 88%

Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes

Manowsky

Camargo

Kipp

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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“…Previous studies have shown that macrophage-conditioned medium inhibited adipogenesis in 3T3-L1 and human preadipocytes (11, 17). Moreover, IL-1β KO mice being high-fat fed (HFF) had lower mRNA levels of proinflammatory factors, increased expression of the adipogenic genes ( Pparγ, Cebpα, Cebpβ, Fabp4 ) in adipose tissue and less hepatic steatosis compared with wild-type HFF mice, which suggests that IL-1β could impair fat storage and promote ectopic fat accumulation by limiting adipose tissue expandability (37).…”

Section: Discussionmentioning

confidence: 91%

Interleukin-1β mediates macrophage-induced impairment of insulin signaling in human primary adipocytes

Gao

Madi

Ding

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

172

127

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Adipose tissue expansion during obesity is associated with increased macrophage infiltration. Macrophage-derived factors significantly alter adipocyte function, inducing inflammatory responses and decreasing insulin sensitivity. Identification of the major factors that mediate detrimental effects of macrophages on adipocytes may offer potential therapeutic targets. IL-1β, a proinflammatory cytokine, is suggested to be involved in the development of insulin resistance. This study investigated the role of IL-1β in macrophage-adipocyte cross-talk, which affects insulin signaling in human adipocytes. Using macrophage-conditioned (MC) medium and human primary adipocytes, we examined the effect of IL-1β antagonism on the insulin signaling pathway. Gene expression profile and protein abundance of insulin signaling molecules were determined, as was the production of proinflammatory cytokine/chemokines. We also examined whether IL-1β mediates MC medium-induced alteration in adipocyte lipid storage. MC medium and IL-1β significantly reduced gene expression and protein abundance of insulin signaling molecules, including insulin receptor substrate-1, phosphoinositide 3-kinase p85α, and glucose transporter 4 and phosphorylation of Akt. In contrast, the expression and release of the proinflammatory markers, including IL-6, IL-8, monocyte chemotactic protein-1, and chemokine (C-C motif) ligand 5 by adipocytes were markedly increased. These changes were significantly reduced by blocking IL-1β activity, its receptor binding, or its production by macrophages. MC medium-inhibited expression of the adipogenic factors and -stimulated lipolysis was also blunted with IL-1β neutralization. We conclude that IL-1β mediates, at least in part, the effect of macrophages on insulin signaling and proinflammatory response in human adipocytes. Blocking IL-1β could be beneficial for preventing obesity-associated insulin resistance and inflammation in human adipose tissue.

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“…The mean age of the patients was 53 ± 9 years and the mean body mass index was 33 ± 10 ( ± SD). The stromal preadipocytes were isolated as previously described [18]. Connective tissue and capillaries were removed by dissection and tissue was digested with collagenase CLS type 1 (200 U/g of tissue; Worthington), followed by sequential size filtration through 200, 100, 50, and 25 μm filters.…”

Section: Human Subcutaneous Preadipocyte Isolation and Culturementioning

confidence: 99%

Interacting Effects of TSH and Insulin on Human Differentiated Adipocytes

2014

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Subclinical hypothyroidism, characterized by an isolated rise in TSH serum levels with normal thyroid function, is a pro-inflammatory state associated with insulin resistance. Adipocytes express TSH receptors, but it is not known if TSH can directly inhibit insulin signaling. Using primary human differentiated adipocytes, we examined the effects of TSH on insulin-stimulated Akt phosphorylation, and whether conventional PKC (cPKC) were involved. The effect of insulin on TSH-stimulated lipolysis was also investigated. TSH inhibited insulin-stimulated Akt phosphorylation in adipocytes by 54%. TSH activated cPKC, and Gö6976, a PKCα and -β1 inhibitor, prevented the inhibitory effect of TSH on the insulin response. Insulin reduced the ability of TSH to activate cPKC and to stimulate lipolysis.Our data reveal novel interactions between TSH and insulin. TSH inhibits insulin-stimulated Akt signaling in a cPKC-dependent fashion, whereas insulin blocks TSH-stimulated cPKC activity and lipolysis. TSH and insulin act on differentiated human adipocytes to modulate their respective intracellular signals.

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The role of interleukin 1β in the anti-adipogenic action of macrophages on human preadipocytes

Cited by 35 publications

References 36 publications

Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes

Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes

Interleukin-1β mediates macrophage-induced impairment of insulin signaling in human primary adipocytes

Interacting Effects of TSH and Insulin on Human Differentiated Adipocytes

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