Proteome analysis of human adipocytes identifies depot-specific heterogeneity at metabolic control points

Raajendiran, Arthe; Souza, David P De; Ooi, Geraldine; Burton, Paul R.; Taylor, Renea A.; Molloy, Mark P.; Watt, Matthew J.

doi:10.1152/ajpendo.00473.2020

Cited by 24 publications

(5 citation statements)

References 76 publications

(86 reference statements)

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“…Previous studies have characterized the proteome of isolated human adipocytes and found massive depot-specific differences ( 43 , 44 ). However, the context of adipocytes in their native environment and the interplay with other cell types is crucial to understand the state of adipose tissue in health and disease.…”

Section: Resultsmentioning

confidence: 99%

High-throughput proteomics uncovers exercise training and type 2 diabetes–induced changes in human white adipose tissue

Larsen,

Kruse,

Sahebekhtiari

et al. 2023

Sci. Adv.

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White adipose tissue (WAT) is important for metabolic homeostasis. We established the differential proteomic signatures of WAT in glucose-tolerant lean and obese individuals and patients with type 2 diabetes (T2D) and the response to 8 weeks of high-intensity interval training (HIIT). Using a high-throughput and reproducible mass spectrometry–based proteomics pipeline, we identified 3773 proteins and found that most regulated proteins displayed progression in markers of dysfunctional WAT from lean to obese to T2D individuals and were highly associated with clinical measures such as insulin sensitivity and HbA1c. We propose that these distinct markers could serve as potential clinical biomarkers. HIIT induced only minor changes in the WAT proteome. This included an increase in WAT ferritin levels independent of obesity and T2D, and WAT ferritin levels were strongly correlated with individual insulin sensitivity. Together, we report a proteomic signature of WAT related to obesity and T2D and highlight an unrecognized role of human WAT iron metabolism in exercise training adaptations.

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Section: Resultsmentioning

confidence: 99%

High-throughput proteomics uncovers exercise training and type 2 diabetes–induced changes in human white adipose tissue

Larsen,

Kruse,

Sahebekhtiari

et al. 2023

Sci. Adv.

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“…The heterogeneity of adipose tissue is driven by differences in sex, genetics and environment, but also by the various depots existing in humans and their cellular composition [57]. It is well known that diversity in morphology, metabolism and function shapes metabolic status, negatively influencing the entire energy balance and controlling the appearance of metabolic diseases [58]. On the other hand, the dynamic interactions of the SVF cells with the milieu through paracrine and endocrine signaling can positively impact the local and systemic responses stimulating anti-inflammatory and proangiogenic activity [59].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Human Subcutaneous Adipose Tissue and Validation of the Banking Procedure for Autologous Transplantation

Favaretto

Compagnin

Cogliati

et al. 2023

IJMS

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Adipose tissue (AT) is composed of a heterogeneous population which comprises both progenitor and differentiated cells. This heterogeneity allows a variety of roles for the AT, including regenerative functions. In fact, autologous AT is commonly used to repair soft tissue defects, and its cryopreservation could be a useful strategy to reduce the patient discomfort caused by multiple harvesting procedures. Our work aimed to characterize the cryopreserved AT and to validate its storage for up to three years for clinical applications. AT components (stromal vascular fraction-SVF and mature adipocytes) were isolated in fresh and cryopreserved samples using enzymatic digestion, and cell viability was assessed by immunofluorescence (IF) staining. Live, apoptotic and necrotic cells were quantified using cytometry by evaluating phosphatidylserine binding to fluorescent-labeled Annexin V. A multiparametric cytometry was also used to measure adipogenic (CD34+CD90+CD31−CD45−) and endothelial (CD34+CD31+CD45−) precursors and endothelial mature cells (CD34−CD31+CD45−). The maintenance of adipogenic abilities was evaluated using in vitro differentiation of SVF cultures and fluorescent lipid staining. We demonstrated that AT that is cryopreserved for up to three years maintains its differentiation potential and cellular composition. Given our results, a clinical study was started, and two patients had successful transplants without any complications using autologous cryopreserved AT.

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“…Adipose tissue plays a central role in energy homeostasis and metabolic function [reviewed in (2,53)], and its development and functions are regulated by insulin signaling (54). Metabolic and functional characteristics differ between adipose tissue depots and their specific contribution to metabolic health and disease is extensively studied (9,14,(55)(56)(57).…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model

et al. 2021

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Adipose tissue (AT) is no longer considered to be responsible for energy storage only but is now recognized as a major endocrine organ that is distributed across different parts of the body and is actively involved in regulatory processes controlling energy homeostasis. Moreover, AT plays a crucial role in the development of metabolic disease such as diabetes. Recent evidence has shown that adipokines have the ability to regulate blood glucose levels and improve metabolic homeostasis. While AT has been studied extensively in the context of type 2 diabetes, less is known about how different AT types are affected by absolute insulin deficiency in type 1 or permanent neonatal diabetes mellitus. Here, we analyzed visceral and subcutaneous AT in a diabetic, insulin-deficient pig model (MIDY) and wild-type (WT) littermate controls by RNA sequencing and quantitative proteomics. Multi-omics analysis indicates a depot-specific dysregulation of crucial metabolic pathways in MIDY AT samples. We identified key proteins involved in glucose uptake and downstream signaling, lipogenesis, lipolysis and β-oxidation to be differentially regulated between visceral and subcutaneous AT in response to insulin deficiency. Proteins related to glycogenolysis, pyruvate metabolism, TCA cycle and lipogenesis were increased in subcutaneous AT, whereas β-oxidation-related proteins were increased in visceral AT from MIDY pigs, pointing at a regionally different metabolic adaptation to master energy stress arising from diminished glucose utilization in MIDY AT. Chronic, absolute insulin deficiency and hyperglycemia revealed fat depot-specific signatures using multi-omics analysis. The generated datasets are a valuable resource for further comparative and translational studies in clinical diabetes research.

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Proteome analysis of human adipocytes identifies depot-specific heterogeneity at metabolic control points

Cited by 24 publications

References 76 publications

High-throughput proteomics uncovers exercise training and type 2 diabetes–induced changes in human white adipose tissue

High-throughput proteomics uncovers exercise training and type 2 diabetes–induced changes in human white adipose tissue

Characterization of Human Subcutaneous Adipose Tissue and Validation of the Banking Procedure for Autologous Transplantation

Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model

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