Characterization of subcutaneous and omental adipose tissue in patients with obesity and with different degrees of glucose impairment

Belligoli, Anna; Compagnin, Chiara; Sanna, Marta; Favaretto, Francesca; Fabris, Roberto; Busetto, Luca; Foletto, Mirto; Prà, Chiara Dal; Serra, Roberto; Prevedello, Luca; Re, Chiara; Bardini, Romeo; Mescoli, Claudia; Rugge, Massimo; Fioretto, Paola; Conci, Scilla; Bettini, Silvia; Milan, Gabriella; Vettor, Roberto

doi:10.1038/s41598-019-47719-y

Cited by 53 publications

(50 citation statements)

References 38 publications

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“…This vicious cycle continues with tumor necrosis factor-alpha and IL-1β secreted by M1 macrophages, further impairing adipogenic differentiation, with reduced adipogenic gene expression in subcutaneous AT and, in some cases, increased numbers of small adipocytes ( 48 , 57 , 58 ). In contrast, normoglycemic obese individuals show an increase in the percent of adipose progenitors within their tissue compared with both pre-diabetic and T2D obese subjects ( 59 ). MHO individuals benefit from a positive insulin sensitizing cycle, where anti-inflammatory signals from adipocytes result in M2 macrophage polarization, which promotes healthy adipocyte hyperplasia and further anti-inflammatory signaling from adipocytes.…”

Section: Adipocyte Function and Adipogenesismentioning

confidence: 99%

“…Increased interstitial fibrosis due to excess collagen deposition likely decreases ECM flexibility and reduces tissue plasticity, which leads to adipocyte dysfunction and immune cell infiltration ( 66 ). Insulin-resistant individuals demonstrate aberrant ECM deposition and insufficient ECM breakdown ( 59 , 67 ).…”

Section: Extracellular Matrix Remodelingmentioning

confidence: 99%

“…Individuals with worsening glycemic control exhibit excess AT deposition of collagens I, III, IV, and VI ( 59 ). Collagen VI gene expression coincides with more visceral adipose mass and pro-inflammatory macrophage accumulation ( 75 , 76 ).…”

Section: Extracellular Matrix Remodelingmentioning

confidence: 99%

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Adipose Tissue Macrophage Polarization in Healthy and Unhealthy Obesity

2021

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Over 650 million adults are obese (body mass index ≥ 30 kg/m2) worldwide. Obesity is commonly associated with several comorbidities, including cardiovascular disease and type II diabetes. However, compiled estimates suggest that from 5 to 40% of obese individuals do not experience metabolic or cardiovascular complications. The existence of the metabolically unhealthy obese (MUO) and the metabolically healthy obese (MHO) phenotypes suggests that underlying differences exist in both tissues and overall systemic function. Macrophage accumulation in white adipose tissue (AT) in obesity is typically associated with insulin resistance. However, as plastic cells, macrophages respond to stimuli in their microenvironments, altering their polarization between pro- and anti-inflammatory phenotypes, depending on the state of their surroundings. The dichotomous nature of MHO and MUO clinical phenotypes suggests that differences in white AT function dictate local inflammatory responses by driving changes in macrophage subtypes. As obesity requires extensive AT expansion, we posit that remodeling capacity with adipose expansion potentiates favorable macrophage profiles in MHO as compared with MUO individuals. In this review, we discuss how differences in adipogenesis, AT extracellular matrix deposition and breakdown, and AT angiogenesis perpetuate altered AT macrophage profiles in MUO compared with MHO. We discuss how non-autonomous effects of remote organ systems, including the liver, gastrointestinal tract, and cardiovascular system, interact with white adipose favorably in MHO. Preferential AT macrophage profiles in MHO stem from sustained AT function and improved overall fitness and systemic health.

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Section: Adipocyte Function and Adipogenesismentioning

confidence: 99%

Section: Extracellular Matrix Remodelingmentioning

confidence: 99%

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Adipose Tissue Macrophage Polarization in Healthy and Unhealthy Obesity

2021

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“…Immunofluorescence (IF) analyses have shown decreased capillary density in the sWAT (number of capillaries/tissue area and number of capillaries/adipocyte) [ 4 ] and vWAT (number of capillaries/tissue area) [ 5 ] of patients with obesity compared to lean subjects. Similarly, immunohistochemical (IHC) analyses showed lower capillary density (number of capillaries/tissue area) in the sWAT and vWAT of normoglycemic, prediabetic and type 2 diabetes mellitus (T2DM) patients with obesity compared to lean subjects [ 6 ]. Moreover, IHC analyses showed lower capillary density (number of capillaries/tissue area and number of capillaries/adipocyte) in the sWAT of patients with obesity compared to overweight patients and ex vivo experiments revealed reduced number of capillary branches in sWAT explants from patients with obesity compared to explants from overweight patients [ 7 ].…”

Section: Obesity-induced Capillary Rarefaction In Different Tissuementioning

confidence: 99%

Capillary Rarefaction in Obesity and Metabolic Diseases—Organ-Specificity and Possible Mechanisms

Paavonsalo

Hariharan

Lackman

et al. 2020

Cells

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Obesity and its comorbidities like diabetes, hypertension and other cardiovascular disorders are the leading causes of death and disability worldwide. Metabolic diseases cause vascular dysfunction and loss of capillaries termed capillary rarefaction. Interestingly, obesity seems to affect capillary beds in an organ-specific manner, causing morphological and functional changes in some tissues but not in others. Accordingly, treatment strategies targeting capillary rarefaction result in distinct outcomes depending on the organ. In recent years, organ-specific vasculature and endothelial heterogeneity have been in the spotlight in the field of vascular biology since specialized vascular systems have been shown to contribute to organ function by secreting varying autocrine and paracrine factors and by providing niches for stem cells. This review summarizes the recent literature covering studies on organ-specific capillary rarefaction observed in obesity and metabolic diseases and explores the underlying mechanisms, with multiple modes of action proposed. It also provides a glimpse of the reported therapeutic perspectives targeting capillary rarefaction. Further studies should address the reasons for such organ-specificity of capillary rarefaction, investigate strategies for its prevention and reversibility and examine potential signaling pathways that can be exploited to target it.

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“…Consistent with this, when adipocyte size is sorted based on size distribution instead of average size, elevated frequency of very small SAT adipocytes and reduced numbers of larger adipocytes were reported in overweight subjects with IR and T2D [ 41 , 44 , 45 ]. However, other studies have also shown increased mean adipocyte size, particularly in VAT, in obese subjects with abnormal metabolic phenotype [ 46 , 47 , 48 ].…”

Section: Healthy and Unhealthy Responses Of Adipose Tissue To Excementioning

confidence: 99%

Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity

Dagpo

Nolan

Delghingaro-Augusto

2020

Cells

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The prevalence of obesity and obesity-related metabolic comorbidities are rapidly increasing worldwide, placing a huge economic burden on health systems. Excessive nutrient supply combined with reduced physical exercise results in positive energy balance that promotes adipose tissue expansion. However, the metabolic response and pattern of fat accumulation is variable, depending on the individual’s genetic and acquired susceptibility factors. Some develop metabolically healthy obesity (MHO) and are resistant to obesity-associated metabolic diseases for some time, whereas others readily develop metabolically unhealthy obesity (MUO). An unhealthy response to excess fat accumulation could be due to susceptibility intrinsic factors (e.g., increased likelihood of dedifferentiation and/or inflammation), or by pathogenic drivers extrinsic to the adipose tissue (e.g., hyperinsulinemia), or a combination of both. This review outlines the major transcriptional factors and genes associated with adipogenesis and regulation of adipose tissue homeostasis and describes which of these are disrupted in MUO compared to MHO individuals. It also examines the potential role of pathogenic insulin hypersecretion as an extrinsic factor capable of driving the changes in adipose tissue which cause transition from MHO to MUO. On this basis, therapeutic approaches currently available and emerging to prevent and reverse the transition from MHO to MUO transition are reviewed.

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Characterization of subcutaneous and omental adipose tissue in patients with obesity and with different degrees of glucose impairment

Cited by 53 publications

References 38 publications

Adipose Tissue Macrophage Polarization in Healthy and Unhealthy Obesity

Adipose Tissue Macrophage Polarization in Healthy and Unhealthy Obesity

Capillary Rarefaction in Obesity and Metabolic Diseases—Organ-Specificity and Possible Mechanisms

Exploring Therapeutic Targets to Reverse or Prevent the Transition from Metabolically Healthy to Unhealthy Obesity

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