scholarly journals Single-Cell Proteomics Reveals the Defined Heterogeneity of Resident Macrophages in White Adipose Tissue

2021 ◽  
Vol 12 ◽  
Author(s):  
Inês Félix ◽  
Heli Jokela ◽  
Joonas Karhula ◽  
Noora Kotaja ◽  
Eriika Savontaus ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
White Adipose Tissue ◽  
Antigen Processing ◽  
Dietary Intervention ◽  
Cell Mass ◽  
Genetic Lineage ◽  
Developmental Origin ◽  
Mhc Ii ◽  
Macrophage Subpopulations

Adipose tissue macrophages (ATMs) regulate homeostasis and contribute to the metabolically harmful chronic inflammation in obese individuals. While evident heterogeneity of resident ATMs has been described previously, their phenotype, developmental origin, and functionality remain inconsistent. We analyzed white adipose tissue (WAT) during homeostasis and diet interventions using comprehensive and unbiased single-cell mass cytometry and genetic lineage tracking models. We now provide a uniform definition of individual subsets of resident ATMs. We show that in lean mice, WAT co-harbors eight kinetically evolving CD206+ macrophage subpopulations (defined by TIM4, CD163, and MHC II) and two CD206– macrophage subpopulations. TIM4–CD163+, TIM4–CD163– and CD206– macrophage populations are largely bone marrow-derived, while the proliferating TIM4+CD163+ subpopulation is of embryonic origin. All macrophage subtypes are active in phagocytosis, endocytosis, and antigen processing in vitro, whereas TIM4+CD163+ cells are superior in scavenging in vivo. A high-fat diet induces massive infiltration of CD206– macrophages and selective down-regulation of MHC II on TIM4+ macrophages. These changes are reversed by dietary intervention. Thus, the developmental origin and environment jointly regulate the functional malleability of resident ATMs.

scholarly journals Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity

2021 ◽  
Vol 22 (5) ◽  
pp. 639-653
Author(s):  
Andrew D. Hildreth ◽  
Feiyang Ma ◽  
Yung Yu Wong ◽  
Ryan Sun ◽  
Matteo Pellegrini ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
White Adipose Tissue ◽  
Single Cell Sequencing

scholarly journals Single cell atlas of beige remodeling of white adipose tissue reveals a myeloid to lymphoid shift during cold exposure compared to beta 3 adrenergic stimulation

2020 ◽  
Author(s):  
Nabil Rabhi ◽  
Anna C. Belkina ◽  
Kathleen Desevin ◽  
Briana Noel Cortez ◽  
Stephen R. Farmer
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
White Adipose Tissue ◽  
Cold Exposure ◽  
Immune Cells ◽  
Drug Targets ◽  
Stromal Vascular Fraction ◽  
Adrenergic Stimulation ◽  
Cellular Dynamics ◽  
Metabolic Complications

SUMMARYWhite adipose tissue (WAT) is a dynamic tissue, which responds to environmental stimuli and dietary cues by changing its morphology and metabolic capacity. The ability of WAT to undergo a beige remodeling has become an appealing strategy to combat obesity and its related metabolic complications. Within the cell mixture that constitutes the stromal vascular fraction (SVF), WAT beiging is initiated through expansion and differentiation of adipocytes progenitor cells, however, the extent of the SVF cellular changes is still poorly understood. Additionally, direct beta 3 adrenergic receptor (Adrb3) stimulation has been extensively used to mimic physiological cold- induced beiging, yet it is still unknown whether Adrb3 activation induces the same WAT remodeling as cold exposure. Here, by using single cell RNA sequencing, we provide a comprehensive atlas of the cellular dynamics during beige remodeling within white adipose tissue. We reveal drastic changes both in the overall cellular composition and transcriptional states of individual cell subtypes between Adrb3- and cold-induced beiging. Moreover, we demonstrate that cold exposure induces a myeloid to lymphoid shift of the immune compartment compared to Adrb3 activation. Further analysis, showed that Adrb3 stimulation leads to activation of the interferon/Stat1 pathways favoring infiltration of myeloid immune cells, while repression of this pathway by cold promotes lymphoid immune cells recruitment. These findings provide new insight into the cellular dynamics during WAT beige remodeling and could ultimately lead to novel strategies to identify translationally-relevant drug targets to counteract obesity and T2D.

scholarly journals Antilipolytic and antilipogenic effects of the CPT-1b inhibitor oxfenicine in the white adipose tissue of rats

2016 ◽  
Vol 311 (4) ◽  
pp. R779-R787 ◽  
Author(s):  
Diane M. Sepa-Kishi ◽  
Michelle V. Wu ◽  
Abinas Uthayakumar ◽  
Arta Mohasses ◽  
Rolando B. Ceddia
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
White Adipose Tissue ◽  
Dietary Intervention ◽  
Specific Inhibitor ◽  
Whole Body ◽  
Sprague Dawley ◽  
Ambulatory Activity ◽  
Fat Depots

Oxfenicine is a carnitine-palmitoyl transferase 1b (CPT-1b)-specific inhibitor that has been shown to improve whole body insulin sensitivity while suppressing fatty acid (FA) oxidation and increasing circulating FA. Because the white adipose tissue (WAT) is an organ that stores and releases FAs, this study investigated whether oxfenicine-induced inhibition of FA oxidation affected adiposity and WAT metabolism in rats fed either low (LF) or high-fat (HF) diets. Following 8 wk of dietary intervention, male Sprague-Dawley rats were given a daily intraperitoneal injection of oxfenicine (150 mg/kg body wt) or vehicle (PBS) for 3 wk. Oxfenicine treatment reduced whole body fat oxidation, body weight, and adiposity, and improved insulin sensitivity in HF-fed rats. All of these effects occurred without alterations in food intake, energy expenditure, and ambulatory activity. In vivo oxfenicine treatment reduced FA oxidation and lipolysis in subcutaneous inguinal (SC Ing) adipocytes, whereas glucose incorporation into lipids (lipogenesis) was significantly reduced in both SC Ing and epididymal (Epid) adipocytes. In summary, our results show that oxfenicine-induced inhibition of CPT-1b markedly affects WAT metabolism, leading to reduced adiposity through a mechanism that involves reduced lipogenesis in the SC Ing and Epid fat depots of rats.

scholarly journals A single cell atlas of human and mouse white adipose tissue

2021 ◽  
Author(s):  
Margo P Emont ◽  
Christopher Jacobs ◽  
Adam L Essene ◽  
Deepti Pant ◽  
Danielle Tenen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Cell Types ◽  
Pressure Control ◽  
Specific Cell ◽  
Nutritional Conditions ◽  
Increased Risk ◽  
Stem And Progenitor Cells

White adipose tissue (WAT), once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic, heterogenous, and involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control, and host defense. High fat feeding and other metabolic stressors cause dramatic changes in adipose morphology, physiology, and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia, and type 2 diabetes (T2D). Here, we provide detailed cellular atlases of human and murine subcutaneous and visceral white fat at single cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells (ASPCs), vascular, and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease, and we provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits, and cell types in the function of WAT across species, depots, and nutritional conditions.

scholarly journals High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2439 ◽  
Author(s):  
Wenbiao Shi ◽  
Maria A. Hegeman ◽  
Atanaska Doncheva ◽  
Melissa Bekkenkamp-Grovenstein ◽  
Vincent C. J. de Boer ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Dietary Intervention ◽  
Metabolic Health ◽  
Sirtuin 1 ◽  
Metabolic Flexibility ◽  
High Dose ◽  
Gene Markers ◽  
Nicotinamide Riboside ◽  
Obesogenic Diet

Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD+) precursor vitamin. The scarce reports on the adverse effects on metabolic health of supplementation with high-dose NR warrant substantiation. Here, we aimed to examine the physiological responses to high-dose NR supplementation in the context of a mildly obesogenic diet and to substantiate this with molecular data. An 18-week dietary intervention was conducted in male C57BL/6JRccHsd mice, in which a diet with 9000 mg NR per kg diet (high NR) was compared to a diet with NR at the recommended vitamin B3 level (control NR). Both diets were mildly obesogenic (40 en% fat). Metabolic flexibility and glucose tolerance were analyzed and immunoblotting, qRT-PCR and histology of epididymal white adipose tissue (eWAT) were performed. Mice fed with high NR showed a reduced metabolic flexibility, a lower glucose clearance rate and aggravated systemic insulin resistance. This was consistent with molecular and morphological changes in eWAT, including sirtuin 1 (SIRT1)-mediated PPARγ (proliferator-activated receptor γ) repression, downregulated AKT/glucose transporter type 4 (GLUT4) signaling, an increased number of crown-like structures and macrophages, and an upregulation of pro-inflammatory gene markers. In conclusion, high-dose NR induces the onset of WAT dysfunction, which may in part explain the deterioration of metabolic health.

scholarly journals Single cell approaches to address adipose tissue stromal cell heterogeneity

2020 ◽  
Vol 477 (3) ◽  
pp. 583-600 ◽  
Author(s):  
Elizabeth A. Rondini ◽  
James G. Granneman
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
Energy Homeostasis ◽  
Therapeutic Benefit ◽  
Lineage Tracing ◽  
Cellular Heterogeneity ◽  
Genetic Lineage ◽  
Immune Functions ◽  
Dynamic Interactions ◽  
Central Function

A central function of adipose tissue is in the management of systemic energy homeostasis that is achieved through the co-ordinated regulation of energy storage and mobilization, adipokine release, and immune functions. With the dramatic increase in the prevalence of obesity and obesity-related metabolic disease over the past 30 years, there has been extensive interest in targeting adipose tissue for therapeutic benefit. However, in order for this goal to be achieved it is essential to establish a comprehensive atlas of adipose tissue cellular composition and define mechanisms of intercellular communication that mediate pathologic and therapeutic responses. While traditional methods, such as fluorescence-activated cell sorting (FACS) and genetic lineage tracing, have greatly advanced the field, these approaches are inherently limited by the choice of markers and the ability to comprehensively identify and characterize dynamic interactions among stromal cells within the tissue microenvironment. Single cell RNA sequencing (scRNAseq) has emerged as a powerful tool for deconvolving cellular heterogeneity and holds promise for understanding the development and plasticity of adipose tissue under normal and pathological conditions. scRNAseq has recently been used to characterize adipose stem cell (ASC) populations and has provided new insights into subpopulations of macrophages that arise during anabolic and catabolic remodeling in white adipose tissue. The current review summarizes recent findings that use this technology to explore adipose tissue heterogeneity and plasticity.

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