Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix

Baker, Nicki A.; Muir, Lindsey A.; Washabaugh, Alexandra R.; Neeley, Christopher K.; Chen, Yu Pu; Flesher, Carmen G.; Vorwald, John; Finks, Jonathan F.; Ghaferi, Amir A.; Mulholland, Michael W.; Varban, Oliver A.; Lumeng, Carey N.; O’Rourke, Robert W.

doi:10.1210/jc.2016-2915

Cited by 34 publications

(39 citation statements)

References 38 publications

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“…Especially the non-cellular structure of the extracellular matrix seems to have a major impact on adipocyte metabolisms and is thus remodeled in diseases (e.g. in diabetes) pointing out the complexity of adipose tissue and the shortcomings of frequently used cell culture models [49,50].…”

Section: Introductionmentioning

confidence: 99%

Examination of ex-vivo viability of human adipose tissue slice culture

et al. 2020

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Obesity is associated with significantly higher mortality rates, and excess adipose tissue is involved in respective pathologies. Here we established a human adipose tissue slice cultures (HATSC) model ex vivo. HATSC match the in vivo cell composition of human adipose tissue with, among others, mature adipocytes, mesenchymal stem cells as well as stroma tissue and immune cells. This is a new method, optimized for live imaging, to study adipose tissue and cell-based mechanisms of obesity in particular. HATSC survival was tested by means of conventional and immunofluorescence histological techniques, functional analyses and live imaging. Surgery-derived tissue was cut with a tissue chopper in 500 μm sections and transferred onto membranes building an air-liquid interface. HATSC were cultured in six-well plates filled with Dulbecco's Modified Eagle's Medium (DMEM), insulin, transferrin, and selenium, both with and without serum. After 0, 1, 7 and 14 days in vitro, slices were fixated and analyzed by morphology and Perilipin A for tissue viability. Immunofluorescent staining against IBA1, CD68 and Ki67 was performed to determine macrophage survival and proliferation. These experiments showed preservation of adipose tissue as well as survival and proliferation of monocytes and stroma tissue for at least 14 days in vitro even in the absence of serum. The physiological capabilities of adipocytes were functionally tested by insulin stimulation and measurement of Phospho-Akt on day 7 and 14 in vitro. Viability was further confirmed by live imaging using Calcein-AM (viable cells) and propidium iodide (apoptosis/necrosis). In conclusion, HATSC have been successfully established by preserving the monovacuolar form of adipocytes and surrounding macrophages and connective tissue. This model allows further analysis of mature human adipose tissue biology ex vivo.

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Section: Introductionmentioning

confidence: 99%

Examination of ex-vivo viability of human adipose tissue slice culture

et al. 2020

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“…Nucleases (DNase, RNase, etc .) cleave nucleotide sequences after cell membrane rupture and help remove nucleic acid residues[ 83 , 84 , 96 - 99 ]. Trypsin and a chelator (such as EDTA) are often used in combination.…”

Section: Different Preparations Of Dammentioning

confidence: 99%

Decellularized adipose matrix provides an inductive microenvironment for stem cells in tissue regeneration

Yang

Qiu

Xiong

et al. 2020

WJSC

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Stem cells play a key role in tissue regeneration due to their self-renewal and multidirectional differentiation, which are continuously regulated by signals from the extracellular matrix (ECM) microenvironment. Therefore, the unique biological and physical characteristics of the ECM are important determinants of stem cell behavior. Although the acellular ECM of specific tissues and organs (such as the skin, heart, cartilage, and lung) can mimic the natural microenvironment required for stem cell differentiation, the lack of donor sources restricts their development. With the rapid development of adipose tissue engineering, decellularized adipose matrix (DAM) has attracted much attention due to its wide range of sources and good regeneration capacity. Protocols for DAM preparation involve various physical, chemical, and biological methods. Different combinations of these methods may have different impacts on the structure and composition of DAM, which in turn interfere with the growth and differentiation of stem cells. This is a narrative review about DAM. We summarize the methods for decellularizing and sterilizing adipose tissue, and the impact of these methods on the biological and physical properties of DAM. In addition, we also analyze the application of different forms of DAM with or without stem cells in tissue regeneration (such as adipose tissue), repair (such as wounds, cartilage, bone, and nerves), in vitro bionic systems, clinical trials, and other disease research.

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“…A consequence of obesity is accumulation of ECM with subsequent impairment of adapting to metabolic changes, resulting in reduced glucose uptake 6 and insulin sensitivity 5 . The ECM composition is modified by a number of ECM degrading enzymes, like matrix metalloproteinases (MMPs), of which MMP-9 is one that are produced and released by adipocytes 7 .…”

Section: Introductionmentioning

confidence: 99%

Markers of remodeling in subcutaneous adipose tissue are strongly associated with overweight and insulin sensitivity in healthy non-obese men

Åkra¹,

Aksnes²,

Flaa³

et al. 2020

Preprint

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Background Alteration in extracellular matrix (ECM) in adipose tissues (AT) has been associated with insulin resistance, diabetes and obesity. Aim To investigate whether selected biomarkers of ECM remodeling in AT associate with the amount and distribution of abdominal AT and with insulin sensitivity and other glucometabolic variables. Materials and Methods Subcutaneous AT and fasting blood samples were collected in 103 middle-aged healthy non-obese men. Gene expression in AT was determined by RT-PCR and distribution of AT by computed tomography, separated into subcutaneous, deep subcutaneous and visceral AT. Circulating levels were determined by ELISA, and insulin sensitivity was measured by glucose clamp technique, assessing glucose disposal rate (GDR). Results Metalloproteinase (MMP)-9, tissue inhibitor of MMP (TIMP)-1 and plasminogen activator inhibitor (PAI)-1 expression in AT correlated significantly to the amount of AT in all compartments (r s =0.41-0.53, all p ≤0.01), and to insulin sensitivity, insulin, C-peptide, waist circumference and body mass index (BMI) (r s =0.25–0.57, all p ≤0.05). When dichotomizing the glucometabolic variables at median levels the expression of MMP-9 was 5.3 fold higher in subjects with insulin sensitivity below median (GDR<6.3mg/kg/min) ( p =0.002) and 3.1 fold higher in subjects with BMI above median level (>23.5kg/m 2 ) ( p =0.013). Galectin-3 did not associate with the amount of AT, but inversely with insulin and c.peptide ((p<0.01m both). Conclusion In our healthy non-obese middle-aged population AT-expressed genes, central in remodeling of ECM, associated strongly with the amount of abdominal AT, overweight and insulin sensitivity, indicating AT-remodeling to be important also in non-obese individuals. The remodeling process seems furthermore to play a central role for glucometabolic disturbances.

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Diabetes-Specific Regulation of Adipocyte Metabolism by the Adipose Tissue Extracellular Matrix

Cited by 34 publications

References 38 publications

Examination of ex-vivo viability of human adipose tissue slice culture

Examination of ex-vivo viability of human adipose tissue slice culture

Decellularized adipose matrix provides an inductive microenvironment for stem cells in tissue regeneration

Markers of remodeling in subcutaneous adipose tissue are strongly associated with overweight and insulin sensitivity in healthy non-obese men

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