4-1BBL signaling promotes cell proliferation through reprogramming of glucose metabolism in monocytes/macrophages

Thai H. Tu, Chu Sook Kim, Il S. Nam-Goong, Chang W. Nam, Young Il Kim, Tsuyoshi Goto, Teruo Kawada, Taesun Park, Jung H. Yoon Park, Zae Y. Ryoo, Jeong W. Park, Hye Seon Choi, Rina Yu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Obesity-induced monocyte/macrophage proliferation and activation play a crucial role in various chronic inflammatory metabolic disorders, such as insulin resistance, diabetes mellitus, and atherosclerosis. 4-1BBL, a member of the tumor necrosis factor superfamily expressed on monocytes/macrophages, provides inflammatory signals to modulate their proliferation, survival, and cytokine release. Previously, we demonstrated that 4-1BBL signaling promotes adipose inflammation through enhancement of macrophage activation. Here, we show that 4-1BBL stimulation on monocytes/macrophages enhanced reprogramming of glucose metabolism in the cells, and that this was accompanied by cell proliferation. 4-1BBL stimulation on macrophages increased glucose uptake, transcript/protein levels of glucose transporter 1 and glycolytic enzymes, and lactate production. It also enhanced transcript levels of genes involved in the pentose phosphate pathway and lipogenesis. The 4-1BBL-induced metabolic reprogramming was mediated by AKT-mammalian target of rapamycin signaling. The effect of 4-1BBL-induced macrophage proliferation was completely abolished by 2-deoxyglucose, a glycolytic inhibitor. These findings suggest that 4-1BBL signaling promotes cell proliferation through reprogramming of glucose metabolism in monocytes/macrophages to support their energy demands and biomass production. The 4-1BBL signaling pathway may be a valid target for controlling macrophage-mediated chronic inflammation in obesity and metabolic diseases.

Original languageEnglish
Pages (from-to)1468-1480
Number of pages13
JournalFEBS Journal
Volume282
Issue number8
DOIs
Publication statusPublished - 2015 Apr 1

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Macrophages
Cell proliferation
Metabolism
Monocytes
Cell Proliferation
Glucose
Macrophage Activation
Obesity
Inflammation
Pentose Phosphate Pathway
Lipogenesis
Facilitative Glucose Transport Proteins
Chemical activation
Metabolic Diseases
Deoxyglucose
Sirolimus
Pentoses
Biomass
Insulin Resistance
Lactic Acid

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tu, T. H., Kim, C. S., Nam-Goong, I. S., Nam, C. W., Kim, Y. I., Goto, T., ... Yu, R. (2015). 4-1BBL signaling promotes cell proliferation through reprogramming of glucose metabolism in monocytes/macrophages. FEBS Journal, 282(8), 1468-1480. https://doi.org/10.1111/febs.13236
Tu, Thai H. ; Kim, Chu Sook ; Nam-Goong, Il S. ; Nam, Chang W. ; Kim, Young Il ; Goto, Tsuyoshi ; Kawada, Teruo ; Park, Taesun ; Yoon Park, Jung H. ; Ryoo, Zae Y. ; Park, Jeong W. ; Choi, Hye Seon ; Yu, Rina. / 4-1BBL signaling promotes cell proliferation through reprogramming of glucose metabolism in monocytes/macrophages. In: FEBS Journal. 2015 ; Vol. 282, No. 8. pp. 1468-1480.
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Tu, TH, Kim, CS, Nam-Goong, IS, Nam, CW, Kim, YI, Goto, T, Kawada, T, Park, T, Yoon Park, JH, Ryoo, ZY, Park, JW, Choi, HS & Yu, R 2015, '4-1BBL signaling promotes cell proliferation through reprogramming of glucose metabolism in monocytes/macrophages', FEBS Journal, vol. 282, no. 8, pp. 1468-1480. https://doi.org/10.1111/febs.13236

4-1BBL signaling promotes cell proliferation through reprogramming of glucose metabolism in monocytes/macrophages. / Tu, Thai H.; Kim, Chu Sook; Nam-Goong, Il S.; Nam, Chang W.; Kim, Young Il; Goto, Tsuyoshi; Kawada, Teruo; Park, Taesun; Yoon Park, Jung H.; Ryoo, Zae Y.; Park, Jeong W.; Choi, Hye Seon; Yu, Rina.

In: FEBS Journal, Vol. 282, No. 8, 01.04.2015, p. 1468-1480.

Research output: Contribution to journalArticle

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T1 - 4-1BBL signaling promotes cell proliferation through reprogramming of glucose metabolism in monocytes/macrophages

AU - Tu, Thai H.

AU - Kim, Chu Sook

AU - Nam-Goong, Il S.

AU - Nam, Chang W.

AU - Kim, Young Il

AU - Goto, Tsuyoshi

AU - Kawada, Teruo

AU - Park, Taesun

AU - Yoon Park, Jung H.

AU - Ryoo, Zae Y.

AU - Park, Jeong W.

AU - Choi, Hye Seon

AU - Yu, Rina

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Obesity-induced monocyte/macrophage proliferation and activation play a crucial role in various chronic inflammatory metabolic disorders, such as insulin resistance, diabetes mellitus, and atherosclerosis. 4-1BBL, a member of the tumor necrosis factor superfamily expressed on monocytes/macrophages, provides inflammatory signals to modulate their proliferation, survival, and cytokine release. Previously, we demonstrated that 4-1BBL signaling promotes adipose inflammation through enhancement of macrophage activation. Here, we show that 4-1BBL stimulation on monocytes/macrophages enhanced reprogramming of glucose metabolism in the cells, and that this was accompanied by cell proliferation. 4-1BBL stimulation on macrophages increased glucose uptake, transcript/protein levels of glucose transporter 1 and glycolytic enzymes, and lactate production. It also enhanced transcript levels of genes involved in the pentose phosphate pathway and lipogenesis. The 4-1BBL-induced metabolic reprogramming was mediated by AKT-mammalian target of rapamycin signaling. The effect of 4-1BBL-induced macrophage proliferation was completely abolished by 2-deoxyglucose, a glycolytic inhibitor. These findings suggest that 4-1BBL signaling promotes cell proliferation through reprogramming of glucose metabolism in monocytes/macrophages to support their energy demands and biomass production. The 4-1BBL signaling pathway may be a valid target for controlling macrophage-mediated chronic inflammation in obesity and metabolic diseases.

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