Macrophage-induced preadipocyte survival depends on signaling through Akt, ERK1/2, and reactive oxygen species

Molgat, André S.D.; Gagnon, AnneMarie; Sorisky, Alexander

doi:10.1016/j.yexcr.2010.10.024

Cited by 15 publications

(14 citation statements)

References 52 publications

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“…It has to be mentioned that treatment of 3T3-L1 cells with conditioned media from J774 macrophages protected fat cells from apoptosis induction (Molgat et al, 2011). This apparent discrepancy to our findings can be explained by differences in apoptosis sensitivity between murine 3T3-L1 cells and human fat cells.…”

Section: Discussioncontrasting

confidence: 99%

“…We suggest that 3T3-L1 cells benefit from macrophagesecreted factors such as PDGF (Molgat et al, 2009) which are known to rescue cells from apoptosis. In M a n u s c r i p t 15 addition, it has been shown that macrophage media stimulate Akt phosphorylation in 3T3-L1 cells (Molgat et al, 2011), further supporting the differences between murine and human cells.…”

Section: Discussionmentioning

confidence: 75%

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An inflammatory micro-environment promotes human adipocyte apoptosis

Keuper

Blüher

Schön

et al. 2011

Molecular and Cellular Endocrinology

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Obesity-associated macrophage infiltration into adipose tissue is responsible for both local and systemic inflammation. Recent findings suggest fat cell apoptosis as an initiator of macrophage recruitment.Here, we investigated the effects of an inflammatory micro-environment on fat cells by using human THP-1 macrophages and SGBS adipocytes. Macrophage-secreted factors induced insulin resistance, inhibited insulin-stimulated Akt phosphorylation, and induced apoptosis of adipocytes. The apoptosisinducing effect was even more pronounced in direct co-cultures of adipocytes and macrophages. Our data suggest a link between insulin resistance and apoptosis sensitivity. Accordingly, pharmacological and genetic inhibition of insulin signaling at the level of Akt2 sensitized adipocytes to apoptosis induction by macrophage-secreted factors.In conclusion, we describe here a novel interaction of macrophages and fat cells, i.e. induction of apoptosis. Our data suggest a feed-forward cycle in which macrophages further drive the inflammatory process by inducing insulin resistance and concomitant apoptosis of adipocytes.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 75%

An inflammatory micro-environment promotes human adipocyte apoptosis

Keuper

Blüher

Schön

et al. 2011

Molecular and Cellular Endocrinology

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“…While 3T3-L1 preadipocytes and adipocytes are sensitive to apoptosis induction by serum deprivation (Magun et al, 1998), human SGBS preadipocytes and adipocytes and also human primary adipocytes are characterized by a general resistance to apoptosis stimuli including serum withdrawal (Fischer-Posovszky et al, 2004). While macrophage-conditioned media stimulated Akt phosphorylation in 3T3-L1 cells (Molgat et al, 2011), Akt phosphorylation was inhibited in our human model system (Keuper et al, 2011) further supporting the differences between murine and human cells.…”

Section: The Past – Summary Of Existing Model Systemssupporting

confidence: 66%

THP-1 Macrophages and SGBS Adipocytes ? A New Human in vitro Model System of Inflamed Adipose Tissue

Keuper¹,

Dzyakanchuk²,

Amrein³

et al. 2011

Front. Endocrin.

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Obesity is associated with an accumulation of macrophages in adipose tissue. This inflammation of adipose tissue is a key event in the pathogenesis of several obesity-related disorders, particularly insulin resistance. Here, we summarized existing model systems that mimic the situation of inflamed adipose tissue in vitro, most of them being murine. Importantly, we introduce our newly established human model system which combines the THP-1 monocytic cell line and the preadipocyte cell strain Simpson–Golabi–Behmel syndrome (SGBS). THP-1 cells, which originate from an acute monocytic leukemia, differentiate easily into macrophages in vitro. The human preadipocyte cell strain SGBS was recently introduced as a unique tool to study human fat cell functions. SGBS cells are characterized by a high capacity for adipogenic differentiation. SGBS adipocytes are capable of fat cell-specific metabolic functions such as insulin-stimulated glucose uptake, insulin-stimulated de novo lipogenesis and β-adrenergic-stimulated lipolysis and they secrete typical adipokines including leptin, adiponectin, and RBP4. Applying either macrophage-conditioned medium or a direct co-culture of macrophages and fat cells, our model system can be used to distinguish between paracrine and cell-contact dependent effects. In conclusion, we propose this model as a useful tool to study adipose inflammation in vitro. It represents an inexpensive, highly reproducible human system. The methods described here can be easily extended for usage of primary human macrophages and fat cells.

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“…How prokineticin-2 contributes to the AT remodeling [41], how it modulates the interaction between the adipocytes, macrophages and endothelial cells to regulate AT expansion [42] remains also to be determined. Circulating prokineticin levels in obese, diabetic and heart failure patients remain to be explored.…”

Section: Resultsmentioning

confidence: 99%

Obesity Peptide: Prokineticin

Nebigil¹

2017

Adiposity - Omics and Molecular Understanding

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Obesity confers an increased risk for cardiovascular renal diseases, diabetes mellitus, nonalcoholic steatohepatitis, musculoskeletal disorders, and cancers. Prokineticin-2 is a peptide hormone, which exists as both a circulating hormone system and a local paracrine-signaling mechanism within various tissues including the brain, kidney, and adipose. It acts on the G-protein-coupled receptors (GPCRs) PKR1 and PKR2. The role of prokineticin-2 in the central nervous system is the control of food intake. Its anorexigenic effect is at least partly through the hypothalamic melanocortin system. Prokineticin-2 also prevents adipose tissue expansion by limiting preadipocyte proliferation and differentiation capacity. Prokineticin-2 signaling is important for insulin capillary passages. It also regulates heart and kidney development and function. Here, we discuss a new obesity peptide prokineticin signaling in central regulation of food intake, adipocyte tissue development, and cardiovascular function. Prokineticin may play a key role in the association between obesity and cardiovascular diseases. We also outline the potential of prokineticin receptor-1 as target for the treatment of obesity and cardiovascular diseases.

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Macrophage-induced preadipocyte survival depends on signaling through Akt, ERK1/2, and reactive oxygen species

Cited by 15 publications

References 52 publications

An inflammatory micro-environment promotes human adipocyte apoptosis

An inflammatory micro-environment promotes human adipocyte apoptosis

THP-1 Macrophages and SGBS Adipocytes ? A New Human in vitro Model System of Inflamed Adipose Tissue

Obesity Peptide: Prokineticin

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