Static mechanical stretching accelerates lipid production in 3T3-L1 adipocytes by activating the MEK signaling pathway

Shoham, Naama; Gottlieb, Ronald H.; Sharabani-Yosef, Orna; Zaretsky, Uri; Benayahu, Dafna; Gefen, Amit

doi:10.1152/ajpcell.00167.2011

Cited by 82 publications

(83 citation statements)

References 81 publications

(96 reference statements)

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“…As opposed to these studies, using a non-destructive imageprocessing-based method, we have recently reported that delivering static mechanical stretching by applying substrate tensile strain (STS) of 12% to 3T3-L1 preadipocytes during the timecourse of differentiation (for about 4 weeks), accelerates the lipid production. 28 We further found that the accelerated adipogenesis in the stretched cultures was associated with activation of the mitogen-activated protein kinase kinase (MEK) signaling pathway. 28 However, it remained unclear which specific levels of STS trigger the accelerated adipogenic response.…”

Section: Introductionmentioning

confidence: 90%

“…28 We further found that the accelerated adipogenesis in the stretched cultures was associated with activation of the mitogen-activated protein kinase kinase (MEK) signaling pathway. 28 However, it remained unclear which specific levels of STS trigger the accelerated adipogenic response.…”

Section: Introductionmentioning

confidence: 90%

“…20,28 When cultures reached 90% confluence, differentiation was induced by changing the GM to differentiation medium (DM) consisting of the GM supplemented with 5 mg/mL insulin (Sigma), 1 mM dexamethasone (Sigma) and 0.5 mM 3-isobutyl-1-methylxanthine (Sigma). Three days after differentiation was first induced, the DM was replaced with supporting medium (SM) consisting of GM supplemented with 5 mg/mL insulin only.…”

Section: Cell Culturesmentioning

confidence: 99%

“…The SM was then changed every 2-3 days during the period of experiments (4 weeks). 20,28 Experimental Design Cells (always younger than passage #11) were subjected to STS of 0%, 3%, 6%, 9%, or 12%, using a cell stretching apparatus (CSA) (Fig. 1) which have been described in our previous publications.…”

Section: Cell Culturesmentioning

confidence: 99%

“…However, it is yet unclear what the effects of the magnitude of the sustained static tensile strains are on adipogenesis, despite the relevance of static (tensile) strains to a sedentary lifestyle (which connects to overweight and obesity), or even to wheelchair-bound individuals in which muscle tissues in the buttocks are gradually being replaced by fat. 31 In other words, given that 12% STS enhanced adipogenesis in adipocytes, 28 it is currently unknown what is the specific level of strain within the 0-12% range which is required to trigger the accelerated adipogenic response. We hence hypothesize that the extent of the adipogenic response to the static strain will depend on the level of the strain delivered to the cultures, and that there may be critical strain values above which adipogenesis accelerates.…”

Section: Introductionmentioning

confidence: 99%

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Large, but not Small Sustained Tensile Strains Stimulate Adipogenesis in Culture

et al. 2011

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Understanding the mechanoresponsiveness of adipocytes and the characteristics of the mechanical stimuli that regulate adipogenesis is critically important in establishing knowledge in regard to the long-term effects of a sedentary lifestyle (or immobility in extreme medical conditions) as well as concerning obesity and related diseases. In this study we subjected 3T3-L1 preadipocytes cultured on elastic substrata to different levels of static equiaxial tensile strains within the physiological range, up to substrate tensile strain (STS) of 12%, while inducing differentiation in the cultures. Based on prior work which revealed that adipogenesis is accelerated in cultures subjected to STS of 12% by activating the mitogen-activated protein kinase kinase signaling pathway, we were specifically interested in identifying the STS levels which trigger this process. We hence monitored the production and accumulation of lipid droplets (LDs) using a non-destructive, image-processing-based method that we have previously developed, for a period of 4 weeks. The experimental data demonstrated accelerated adipogenesis in the cultures subjected to STS levels of 6%, 9%, and 12% with respect to cultures subjected to STS of 3% and (non-stretched) control cultures. This accelerated adipogenic response to the large sustained STS manifested in significantly larger numbers and greater sizes of LDs in the cultures that were stretched to large STS levels (p < 0.05), starting at approximately day 14 following induction of differentiation. Hence, indeed, there appears to be a certain tensile strain threshold, or domain-which is found within the physiological range-above which the responsiveness of adipocytes to sustained static stretching increases and is manifested in accelerated adipogenesis.

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Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 90%

Section: Cell Culturesmentioning

confidence: 99%

Section: Cell Culturesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Large, but not Small Sustained Tensile Strains Stimulate Adipogenesis in Culture

et al. 2011

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Establishment and characterization of a primary murine adipose tissue‐chip

Tanataweethum

Zelaya

Yang

et al. 2018

Biotech & Bioengineering

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Better experimental models are needed to enhance our understanding of metabolic regulation which is seen in obesity and metabolic disorders, such as type 2 diabetes. In vitro models based on microfluidics enable physiological representations of tissues with several advantages over conventional culture systems, such as perfused flow to better mimic the physiological environment. Although cell lines such as 3T3-L1 have been incorporated in microfluidic devices, murine primary preadipocytes have not been differentiated and maintained for long-term monitoring in these culture systems. We describe the differentiation of these cells into white adipose depots on a perfused microfluidic chip. We compare the effects of shear flow on these cells, and show with a direct comparison of high/low shear conditions that direct shear is detrimental to the viability of preadipocytes. We further develop a dual-chamber microfluidic chip that enables perfusion while at the same time protects the cells from direct fluidic shear. We show that the dual-layer microfluidic device enables long-term culture of cells and allows stimulation of cells through perfusion-we can culture, differentiate, and maintain the differentiated adipose tissue for over multiple weeks in the device. Both triglycerides and lipolytic glycerol production increased significantly by several folds during differentiation. After successful differentiation, the adipocytes had upregulated expression of leptin and adiponectin, which are important makers of the final stage of adipogenic differentiation. In conclusion, the dual-layer microfluidic device incorporated with primary adipocytes improves the understanding of adipose differentiation under dynamic conditions and is positioned to serve as a disease model for studying obesity and other metabolic disorders.

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Cell shape alteration during adipogenesis is associated with coordinated matrix cues

Moldovan

Lustig

Naftaly

et al. 2018

Journal Cellular Physiology

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Obesity has become one of the leading pathophysiologic disorders in recent years. Adipose tissue is the main tissue related to obesity and is known to play a role in various physiological complications, including type 2 diabetes. To better understand how the fat tissue develops, we used an in vitro live cell imaging system to quantify the adipogenesis by means of nondestructive digital imaging to monitor the accumulation of intracellular lipid droplets (LDs), a hallmark of adipogenesis, from the macro- to the micro-scale. Analyzing the cells' shape at the single-cell level allows to quantify the cells' shape change from a fibroblast to spherical morphology, indicating the start of adipogenesis. To reveal the molecular alterations, we applied a proteomic approach using high-resolution mass spectrometry of the proliferation, confluent fibroblasts and of adipocytes. During this process, we noted the reorganization of the cells' extracellular matrix (ECM) network microenvironment from fibrillary collagen types I, III and V to collagens IV and VI, which affected the cells niche. The changes in ECM are translated for cytoskeleton remodeling according to cell fate-determining mechanisms. We quantified the cytoskeleton rearrangement of long oriented actin fibers or short cortical and disorganized fibers, associated with LDs accumulation in adipocytes. Developing in vitro models and analytical methods enable us to study differentiation into adipocytes that will advance our understanding regarding the niche conditions that affect adipogenesis. Consequently, this will enable the development of new modalities to prevent obesity and its deleterious outcomes and to develop potential treatments to battle pathophysiology-related diseases.

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Static mechanical stretching accelerates lipid production in 3T3-L1 adipocytes by activating the MEK signaling pathway

Cited by 82 publications

References 81 publications

Large, but not Small Sustained Tensile Strains Stimulate Adipogenesis in Culture

Large, but not Small Sustained Tensile Strains Stimulate Adipogenesis in Culture

Establishment and characterization of a primary murine adipose tissue‐chip

Cell shape alteration during adipogenesis is associated with coordinated matrix cues

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