Exploring the activated adipogenic niche: Interactions of macrophages and adipocyte progenitors

Lee, Yun Hee; Thacker, Robert I.; Hall, Brian E.; Kong, Raymond; Granneman, James G.

doi:10.4161/cc.27647

Cited by 38 publications

(45 citation statements)

References 48 publications

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“…As mentioned above, it was previously reported that adipose tissue remodeling by β 3-adrenergic stimulation required non-inflammatory removal of dying adipocytes by macrophages to support proliferation and differentiation of adipocyte progenitors, 6, 22 which served as adipogenic niches. 22 Thus, it was hypothesized that if Alox15 expression is required for the clearance of adipocyte death, then remodeling of adipose tissue by β 3-adrenergic stimulation should be impaired in Alox15 KO mice.…”

Section: Resultsmentioning

confidence: 90%

The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling

et al. 2016

Cell Death Dis

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Cellular plasticity in adipose tissue involves adipocyte death, its clearance, and de novo adipogenesis, enabling homeostatic turnover and adaptation to metabolic challenges; however, mechanisms regulating these serial events are not fully understood. The present study investigated the roles of arachidonate 15-lipoxygenase (Alox15) in the clearance of dying adipocytes by adipose tissue macrophages. First, upregulation of Alox15 expression and apoptotic adipocyte death in gonadal white adipose tissue (gWAT) were characterized during adipose tissue remodeling induced by β3-adrenergic receptor stimulation. Next, an in vitro reconstruction of adipose tissue macrophages and apoptotic adipocytes recapitulated adipocyte clearance by macrophages and demonstrated that macrophages co-cultured with apoptotic adipocytes increased the expression of efferocytosis-related genes. Genetic deletion and pharmacological inhibition of Alox15 diminished the levels of adipocyte clearance by macrophages in a co-culture system. Gene expression profiling of macrophages isolated from gWAT of Alox15 knockout (KO) mice demonstrated distinct phenotypes, especially downregulation of genes involved in lipid uptake and metabolism compared to wild-type mice. Finally, in vivo β3-adrenergic stimulation in Alox15 KO mice failed to recruit crown-like structures, a macrophage network clearing dying adipocytes in gWAT. Consequently, in Alox15 KO mice, proliferation/differentiation of adipocyte progenitors and β3-adrenergic remodeling of gWAT were impaired compared to wild-type control mice. Collectively, our data established a pivotal role of Alox15 in the resolution of adipocyte death and in adipose tissue remodeling.

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Section: Resultsmentioning

confidence: 90%

The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling

et al. 2016

Cell Death Dis

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“…Although extensive evidence has demonstrated that imbalance in M1/M2 Mφs is involved in catabolic remodelling of adipose tissue and contributes to proinflammatory environments that might lead to insulin resistance , the effect of polarized Mφs on adipogenic differentiation of BMMSCs has to our knowledge not yet been reported. In the current study, we found that secreted factors derived from M1‐polarized Mφs enhanced the formation of lipid droplets and expression of adipogenesis‐related genes, such as adiponectin and PPAR‐ γ (Fig.…”

Section: Discussionmentioning

confidence: 98%

The effects of conditioned media generated by polarized macrophages on the cellular behaviours of bone marrow mesenchymal stem cells

Yin

et al. 2017

J Cellular Molecular Medi

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Macrophages (Mφs) are involved in a variety of physiological and pathological events including wound healing and tissue regeneration, in which they play both positive and negative roles depending on their polarization state. In this study, we investigated the cellular behaviours of bone marrow mesenchymal stem cells (BMMSCs) after incubation in different conditioned media (CMs) generated by unpolarized Mφs (M0) or polarized Mφs (M1 and M2). Mφ polarization was induced by stimulation with various cytokines, and CMs were obtained from in vitro Mφ cultures termed CM0, CM1 and CM2 based on each Mφ phenotype. We found that CM1 supported the proliferation and adipogenic differentiation of BMMSCs, whereas CM0 had a remarkable effect on cell osteogenic differentiation. To a certain degree, CM2 also facilitated BMMSC osteogenesis; in particular, cells incubated with CM2 exhibited an enhanced capacity to form robust stem cell sheets. Although incubation with CM1 also increased production of extracellular matrix components, such as fibronectin, COL-1 and integrin b1during sheet induction, the sheets generated by CM2-incubated cells were thicker than those generated by CM1-incubated cells (P < 0.001). Our data suggest that each Mφ phenotype has a unique effect on BMMSCs. Fine-tuning Mφ polarization following transplantation may serve as an effective method to modulate the therapeutic potential of BMMSCs.

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“…Differentiation of pre-adipocytes into beige adipocytes is an important way to increase hBAT activity [28, 29], and the ADRB3 signaling pathway also plays a role in this process. The present study also examined SV cell ADRB3 mRNA and protein expression in overweight individuals to explore whether a disorder of beige adipocyte differentiation was involved.…”

Section: Discussionmentioning

confidence: 99%

Adipocyte ADRB3 Down-Regulated in Chinese Overweight Individuals Adipocyte ADRB3 in Overweight

et al. 2018

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Objectives: Activation of β3-adrenoceptor (ADRB3) is essential in the process of human adipose tissue browning, but obese subjects suffered from reduced ability of brown adipose tissue activation. The present study aims to detect the adipocyte ADRB3 expression in overweight individuals and the relationship between adipocyte ADRB3 expression and adiposity in adults. Methods: Visceral adipose tissue samples were obtained from 85 subjects who underwent abdominal surgery. ADRB3 mRNA and protein expression levels in mature adipocytes and adipose tissue stromal vascular cells were examined by quantitative real-time PCR and Western blot assay, respectively. UCP-1mRNA expression levels in mature adipocytes were examined by quantitative real-time PCR. Results: The data revealed that ADRB3 mRNA (p = 0.021) and protein (p = 0.025) expression levels in mature adipocytes were significantly higher in the normal-weight than in the overweight group. Similar results were also found for ADRB3 mRNA (p = 0.041) and protein (p = 0.025) expressions of stromal vascular cells. An inverse correlation was verified between mature adipocyte ADRB3 mRNA expression and BMI (r = –0.362, p = 0.012). UCP-1 mRNA expression levels in mature adipocytes were higher in the normal-weight group compared with the overweight group (p = 0.045). Conclusion: Adipocyte ADRB3 expression levels were down-regulated before the onset of obesity, which indicated that the reduction of ADRB3 expression might be the cause of compromised adipose tissue browning and obesity rather than the result. Thus, the interference of the ADRB3 pathway in adipocytes may provide a potential treatment target for obesity.

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Exploring the activated adipogenic niche: Interactions of macrophages and adipocyte progenitors

Cited by 38 publications

References 48 publications

The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling

The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling

The effects of conditioned media generated by polarized macrophages on the cellular behaviours of bone marrow mesenchymal stem cells

Adipocyte ADRB3 Down-Regulated in Chinese Overweight Individuals Adipocyte ADRB3 in Overweight

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