An inflammatory micro-environment promotes human adipocyte apoptosis

Keuper, Michaela; Blüher, Matthias; Schön, Michael P.; Möller, Peter; Dzyakanchuk, Anna; Amrein, Kurt E.; Debatin, Klaus‐Michael; Wabitsch, Martin; Fischer‐Posovszky, Pamela

doi:10.1016/j.mce.2011.04.004

Cited by 53 publications

(49 citation statements)

References 48 publications

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“…For these studies, we used predominantly qPCR and FACS-based approaches to classify the infiltrating cells based on these markers [28]. Based on this analysis and consistent with the results reported here, we observed CLS formation with lipid resorbing macrophages.…”

Section: Discussionsupporting

confidence: 78%

Time course of histomorphological changes in adipose tissue upon acute lipoatrophy

Murano¹,

Rutkowski

Wang

et al. 2013

Nutrition, Metabolism and Cardiovascular Diseases

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SUMMARY Background and Aims Crown-like structures (CLS) are characteristic histopathology features of inflamed adipose tissues in obese mice and humans. In previous work, we suggested that these cells derived from macrophages primarily involved in the reabsorption of dead adipocytes. Here, we used a well-characterized transgenic mouse model in which the death of adipocytes in adult mice is inducible and highly synchronized. In this “FAT-ATTAC” model, apoptosis is induced through forced dimerization of a caspase-8 fusion protein. Methods and Results 0, 0.5, 1, 2, 3 and 10 days post induction of adipocyte cell death, we analyzed mesenteric and epididymal adipose depots by histology, immunohistochemistry and electron microscopy. Upon induction of caspase-8 dimerization, numerous adipocytes lost immunoreactivity for perilipin, a marker for live adipocytes. In the same areas, we found adipocytes with hypertrophic mitochondria and signs of organelle degeneration. Neutrophils and lymphocytes were the main inflammatory cells present in the tissue, and the macrophages were predominantly Mac-2 negative. Over the course of ablation, Mac-2 positive macrophages substituted for Mac-2 negative macrophages, followed by CLS formation. All perilipin-negative, dead adipocytes were surrounded by CLS structures. The time course of histopathology was similar in both fat pads studied, but occurred at earlier stages and was more gradual in mesenteric fat. Conclusion Our data demonstrate that CLS formation results as a direct consequence of adipocyte death, and that infiltrating macrophages actively uptake remnant lipids of dead adipocytes. Upon induction of adipocyte apoptosis, inflammatory cells infiltrate adipose tissue initially consisting of neutrophils followed by macrophages that are involved in CLS formation.

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Section: Discussionsupporting

confidence: 78%

Time course of histomorphological changes in adipose tissue upon acute lipoatrophy

Murano¹,

Rutkowski

Wang

et al. 2013

Nutrition, Metabolism and Cardiovascular Diseases

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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: 64%

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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“…Indeed, adipocyte apoptosis increases under high fat diet conditions in rodent models and in individuals with obesity [83,84]. Cellular components, cell-free DNA and/or the exposed lipid droplet may attract immune cells into adipose tissue.…”

Section: Autophagy Apoptosis and Immune Cell Infiltration In Adiposementioning

confidence: 99%

Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?

2016

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The worldwide obesity epidemic has become a major health concern, because it contributes to higher mortality due to an increased risk for noncommunicable diseases including cardiovascular diseases, type 2 diabetes, musculoskeletal disorders and some cancers. Insulin resistance may link accumulation of adipose tissue in obesity to metabolic diseases, although the underlying mechanisms are not completely understood. In the past decades, data from human studies and transgenic animal models strongly suggested correlative, but also causative associations between activation of proinflammatory pathways and insulin resistance. Particularly chronic inflammation in adipose tissue seems to play an important role in the development of obesity-related insulin resistance. On the other hand, adipose tissue inflammation has been shown to be essential for healthy adipose tissue expansion and remodelling. However, whether adipose tissue inflammation represents a consequence or a cause of impaired insulin sensitivity remains an open question. A better understanding of the molecular pathways linking excess adipose tissue storage to chronic inflammation and insulin resistance may provide the basis for the future development of anti-inflammatory treatment strategies to improve adverse metabolic consequences of obesity. In this review, potential mechanisms of adipose tissue inflammation and how adipose tissue inflammation may cause insulin resistance are discussed.

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An inflammatory micro-environment promotes human adipocyte apoptosis

Cited by 53 publications

References 48 publications

Time course of histomorphological changes in adipose tissue upon acute lipoatrophy

Time course of histomorphological changes in adipose tissue upon acute lipoatrophy

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

Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?

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