Non-invasive Assessments of Adipose Tissue Metabolism In Vitro

Abbott, Rosalyn D.; Borowsky, Francis E.; Quinn, Kyle P.; Bernstein, Douglas A.; Georgakoudi, Irene

doi:10.1007/s10439-015-1438-9

Cited by 7 publications

(7 citation statements)

References 62 publications

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“…For SHG imaging, photons emitted at 400 ± 10 nm were detected using a non-descanned photomultiplier tube detector. Endogenous TPEF emitted by chondrocytes was detected at 525 ± 25 nm [48][49][50][51][52]. A water-immersion 63x objective (NA 1.2; 220 μm working distance) was used for articular cartilage imaging.…”

Section: Light Microscopymentioning

confidence: 99%

“…Thus, we performed SHG imaging to investigate changes in collagen fibers in OA progression. To visualize chondrocytes, we performed two-photon excited fluorescence microscopy imaging at the same time, in which endogenous fluorescence from the coenzyme FAD could be obtained, indicating cells within the matrix [48,49,[53][54][55][56] (Fig. 4a).…”

Section: Second Harmonic Generation Imaging Indicates Reduced Collagementioning

confidence: 99%

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Bioluminescence and second harmonic generation imaging reveal dynamic changes in the inflammatory and collagen landscape in early osteoarthritis

Mingalone¹,

Liu²,

Hollander³

et al. 2018

Laboratory Investigation

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Osteoarthritis (OA) is a leading cause of chronic disability whose mechanism of pathogenesis is largely elusive. Local inflammation is thought to play a key role in OA progression, especially in injury-associated OA. While multiple inflammatory cytokines are detected, the timing and extent of overall inflammatory activities in early OA and the manner by which joint inflammation correlates with cartilage structural damage are still unclear. We induced OA via destabilization of the medial meniscus (DMM) in NFκB luciferase reporter mice, whose bioluminescent signal reflects the activity of NFκB, a central mediator of inflammation. Bioluminescence imaging data showed that DMM and sham control joints had a similar surge of inflammation at 1-week post-surgery, but the DMM joint exhibited a delay in resolution of inflammation in subsequent weeks. A similar trend was observed with synovitis, which we found to be mainly driven by synovial cell density and inflammatory infiltration rather than synovial lining thickness. Interestingly, an association between synovitis and collagen structural damage was observed in early OA. Using Second Harmonic Generation (SHG) imaging, we analyzed collagen fiber organization in articular cartilage. Zonal differences in collagen fiber thickness and organization were observed as soon as OA initiated after DMM surgery, and persisted over time. Even at 1-week post-surgery, the DMM joint showed a decrease in collagen fiber thickness in the deep zone and an increase in collagen fiber disorganization in the superficial zone. Since we were able detect and quantify collagen structural changes very early in OA development by SHG imaging, we concluded that SHG imaging is a highly sensitive tool to evaluate pathological changes in OA. In summary, this study uncovered a dynamic profile of inflammation and joint cartilage damage during OA initiation and development, providing novel insights into OA pathology.

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Section: Light Microscopymentioning

confidence: 99%

Section: Second Harmonic Generation Imaging Indicates Reduced Collagementioning

confidence: 99%

Bioluminescence and second harmonic generation imaging reveal dynamic changes in the inflammatory and collagen landscape in early osteoarthritis

Mingalone¹,

Liu²,

Hollander³

et al. 2018

Laboratory Investigation

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“…For use as a patient‐specific model, non‐destructive analyses are essential for obtaining data without increasing the sample size of the study and to track multiple data points on the same sample. In particular, non‐destructive monitoring techniques show promise for adipose tissue systems (Abbott et al, ). For exploring treatment strategies, adverse effects to drugs, disease mechanisms, and other responses that vary between patients, non‐destructive techniques will be essential to validate that each tissue construct is properly seeded and maintains the proper mature unilocular adipocyte phenotype before proceeding with other tests.…”

Section: Resultsmentioning

confidence: 99%

Variability in responses observed in human white adipose tissue models

Abbott

Borowsky

Alonzo

et al. 2017

J Tissue Eng Regen Med

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Obesity is a risk factor for a myriad of diseases including diabetes, cardiovascular dysfunction, cirrhosis, and cancer, and there is a need for new systems to study how excess adipose tissue relates to the onset of disease processes. This study provides proof-of-concept patient-specific tissue models of human white adipose tissue to accommodate the variability in human samples. Our 3D tissue engineering approach established lipolytic responses and changes in insulin-stimulated glucose uptake from small volumes of human lipoaspirate, making this methodology useful for patient specific sample source assessments of treatment strategies, drug responses, disease mechanisms, and other responses that vary between patients. Mature unilocular cells were maintained ex vivo in silk porous scaffolds for up to a month of culture and imaged non-invasively with coherent anti-Stokes Raman scattering. Interestingly, differences in responsiveness between tissues were observed in terms of magnitude of lipolysis, ability to suppress lipolysis, differences in glucose uptake, and lipid droplet size. Body mass index was not a factor in determining tissue responsiveness; rather, it is speculated that other unknown variables in the backgrounds of different patients (ethnicity, athleticism, disease history, lifestyle choices, etc.) likely had a more significant effect on the observed differences. This study reinforces the need to account for the variability in backgrounds and genetics within the human population to determine adipose tissue responsiveness. In the future, this tissue system could be used to inform individualized care strategies-enhancing therapeutic precision, improving patient outcomes, and reducing clinical costs.

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“…However, a protective role of the adipose tissue in certain clinical conditions has been described, giving rise to the "obesity paradox", de ned as the duality behavior of the adipose tissue [18]. Until now, most of the studies carried out on AT have been performed by using non-invasive imaging technologies such as MRI, X-ray or ultrasound [19][20][21] as well as in different animal models. However, some limitations appear when animal ndings are translated to human studies [22,23].…”

Section: Discussionmentioning

confidence: 99%

Untargeted and Targeted Proteomic Analysis of the Impact of Diabetes Mellitus on Two Adipose Tissue Depots and Blood of Obese Patients

Arderiu

Lambert

Padró

et al. 2020

Preprint

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Background: Obesity has increased over the last years and it is one of the most common cardiovascular risk factors. In addition obesity is associated with the development of other metabolic disorders such as insulin resistance and type-2 diabetes mellitus (T2DM). Here, we have investigated two adipose tissue depots (AT) proteome and secreted serum proteins in obese patients to understand fat tissue characteristics in metabolic syndrome and T2DM.Methods: We used an untargeted proteomic approach to compare white AT of subcutaneous (SAT) and visceral (VAT) depots in type 3 obese patients. In silico analysis and bioinformatics were applied to proteomic data to gain systems biology information. By bead-based targeted multiplex assay system, we simultaneously detected and quantified multiple targets in qualified complex samples and analyzed the changes produced in the adipokine serum composition due to obesity and T2DM.Results: Protein composition in SAT and VAT showed significant differences. There was upregulation of proteins related with the endocrine regulation system in SAT, whereas proteins upregulated in VAT were related to metabolic disorders. VAT protein composition was more sensitive to the presence of diabetes than SAT. A pro-inflammatory state, caused by the secretion of cytokines and related adypokines, was observed in the serum protein composition of both obese and diabetic patients.Conclusions: Our results show a synergic alteration in the metabolic and inflammatory state in both VAT and serum due to the presence of diabetes, whereas changes in SAT were related with endocrine regulation.

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Non-invasive Assessments of Adipose Tissue Metabolism In Vitro

Cited by 7 publications

References 62 publications

Bioluminescence and second harmonic generation imaging reveal dynamic changes in the inflammatory and collagen landscape in early osteoarthritis

Bioluminescence and second harmonic generation imaging reveal dynamic changes in the inflammatory and collagen landscape in early osteoarthritis

Variability in responses observed in human white adipose tissue models

Untargeted and Targeted Proteomic Analysis of the Impact of Diabetes Mellitus on Two Adipose Tissue Depots and Blood of Obese Patients

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