Relation between Age of Onset of Obesity and Size and Number of Adipose Cells

Brook, C. G. D.; Lloyd, June K.; Wolf, Olivia

doi:10.1136/bmj.2.5804.25

Cited by 208 publications

(84 citation statements)

References 15 publications

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“…49 The plausibility of this hypothesis becomes evident when one considers the fact that, during the development of obesity, adipocytes can hypertrophy to diameters nearly twice the diffusion limit of oxygen into cells. 50,51 We first tested this premise indirectly by quantifying the expression of adipose genes known to be upregulated by hypoxic conditions, namely HIF-1a, HIF-2a and GLUT-1. [52][53][54][55] Consistent with our hypothesis, we noted their expression to be increased by quantitative real-time PCR in the adipose tissue of both DIO and ob/ob mice as compared to lean controls.…”

Section: Discussionmentioning

confidence: 99%

Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration

et al. 2007

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Background: Obesity is currently viewed as a state of chronic low-grade inflammation in which there is a pro-inflammatory alteration in the serum adipocytokine profile as well as an infiltration of white adipose tissue by activated macrophages. The etiology of this inflammation, however, is poorly understood. Methods: Hypothesizing that local hypoxia within expanding white adipose tissue depots may contribute to obesity-related inflammation, we compared body composition, serum inflammatory marker concentrations and the expression of several hypoxia-regulated genes in white adipose tissue derived from lean, dietary-induced obese (DIO) and ob/ob male C57BL/6J mice. We also examined white adipose tissue for the presence of hypoxia using both a pimonidazole-based antibody system and a fiberoptic sensor for real-time pO 2 quantification in vivo. Finally, using cell-specific leukocyte antibodies, we performed immunohistochemistry and flow cytometric analyses to further characterize the cellular nature of adipose inflammation. Results: We determined that obesity in male C57BL/6J mice is associated with increased expression of HIF (hypoxia-inducible factor) isoforms and GLUT-1, and that white adipose tissue hypoxia was present in the obese mice. Immunohistochemistry revealed hypoxic areas to colocalize predominantly with F4/80 þ macrophages. Interestingly, CD3 þ T cells were present in large numbers within the adipose of both DIO and ob/ob obese mice, and flow cytometry revealed their adipose to possess significantly more CD8 þ T cells than their lean cohort. Conclusions: White adipose hypoxia and cytotoxic T-cell invasion are features of obesity in C57BL/6J mice and are potential contributors to their local and generalized inflammatory state.

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Section: Discussionmentioning

confidence: 99%

Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration

et al. 2007

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“…Accordingly, adipocytes are emerging as a potential therapeutic target for obesity, type 2 diabetes and cardiovascular disease (15). Adipose tissue mass reflects the number and average volume of adipocytes, in particular the balance between cell acquisition and cell loss (16)(17)(18). The proliferation of adipocyte precursors and their differentiation into mature adipocytes contribute to the development of obesity in mammals.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of C10orf116 promotes proliferation, inhibits apoptosis and enhances glucose transport in 3T3-L1 adipocytes

Chen

Zhou

et al. 2013

Molecular Medicine Reports

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Abstract. Data from our previous study demonstrated thatC10orf116 is an adipocyte lineage-specific nuclear factor, which regulates master adipogenesis transcription factors during early differentiation. However, the precise functional properties of this gene have yet to be identified and further investigation is required. In the present study, we report the effects of C10orf116 expression on cell proliferation and apoptosis in vitro and observed that the overexpression of C10orf116 stimulates proliferation and inhibits apoptosis in preadipocytes. Furthermore, we investigated the effects of C10orf116 on glucose uptake and demonstrated that the ectopic expression of C10orf116 significantly increases insulin-stimulated glucose uptake in adipocytes by increasing glucose transporter type 4 (GLUT4) expression levels. Collectively, these data further support the hypothesis that C10orf116 is important in regulating glucose transport in adipocytes as well as the number of preadipocytes. The results of the present study may also provide insights into the complex mechanisms involved in the development of obesity.

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“…Studies show that markers of ER stress and UPR are elevated in tissues from diabetic and/or obese humans and rodents [78,[82][83][84]. The enormous adipocyte size, accumulation of lipids and increased cellularity of adipose tissue in obesity are thought to contribute to local tissue hypoxia [85].…”

Section: Proteotoxic Stress In the Pathogenesis Of Diseases Not Formementioning

confidence: 99%

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond

et al. 2015

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Cells have a number of mechanisms to maintain protein homeostasis, including proteasomemediated degradation of ubiquitinated proteins and autophagy, a regulated process of 'self-eating' where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by tolllike receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses.Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis.3 Cells must maintain a delicate balance between the demands for protein synthesis and the need to avoid accumulation of incompletely processed or unfolded proteins that can accumulate under normal conditions and even more so when cells face a variety of stresses. The unfolded protein response (UPR) is an evolutionarily conserved mechanism to maintain cellular homeostasis by preventing the accumulation of misfolded proteins in the endoplasmic reticulum (ER). Disturbed protein folding in the ER is primarily detected by three transmembrane (TM) proteins: activating transcription factor 6 (ATF6), inositol-requiring transmembrane kinase/endonuclease 1 (IRE1) and pancreatic ER kinase (PERK). The combined action of these sensors reduces global protein synthesis while upregulating the production of chaperone proteins that can stabilize misfolded proteins. Apart from ER homeostasis, the UPR can modulate other biological functions, including apoptosis, protein secretion, and as we will discuss further, inflammatory responses [1,2].A series of molecular changes are initiated in response to cellular stressors in order to minimize damage caused by unfavorable environmental conditions, such as temperature changes, toxins (e.g. bacterial, chemical), radiation, mechanical damage, nutritional status as well as incompletely folded proteins intracellularly (Figure 1). The UPR serves the adaptive purpose of protecting the cell by activating a series of mechanisms including the induction of molecular chaperones to assist with correct folding -e.g. heat shock proteins and foldases. Interestingly there are a number of connections between the UPR and inflammatory signaling pat...

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Relation between Age of Onset of Obesity and Size and Number of Adipose Cells

Cited by 208 publications

References 15 publications

Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration

Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration

Overexpression of C10orf116 promotes proliferation, inhibits apoptosis and enhances glucose transport in 3T3-L1 adipocytes

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond

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