Phenotypic and functional features of B cells from two different human subcutaneous adipose depots

Frasca, Daniela; Garcia, Denisse; Diaz, Alain; Romero, Maria; Thaller, Seth R.; Blomberg, Bonnie B.

doi:10.1371/journal.pone.0285025

Cited by 7 publications

(7 citation statements)

References 76 publications

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“…We previously demonstrated that activated splenic B cells isolated from obese mice secreted less IgM and IgG relative to naive controls [39]. Others have also shown that B cell functional responses and phenotypes are dysregulated with obesity or obesity-related complications relative to controls [7,10,[40][41][42][43][44][45][46]. The objective here was to establish a proof of concept that sets the stage for future experiments focused on how obesity impairs mitochondrial respiratory activity of specific B cell subsets to impair humoral immunity and drive inflammation and insulin resistance.…”

Section: Discussionmentioning

confidence: 96%

High Fat Diet-Induced Obesity Dysregulates Splenic B Cell Mitochondrial Activity

Pal,

Lin,

Boykov

et al. 2023

Nutrients

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Diet-induced obesity impairs mitochondrial respiratory responses in tissues that are highly metabolically active, such as the heart. However, less is known about the impact of obesity on the respiratory activity of specific cell types, such as splenic B cells. B cells are of relevance, as they play functional roles in obesity-induced insulin resistance, inflammation, and responses to infection. Here, we tested the hypothesis that high-fat-diet (HFD)-induced obesity could impair the mitochondrial respiration of intact and permeabilized splenic CD19+ B cells isolated from C57BL/6J mice and activated ex vivo with lipopolysaccharide (LPS). High-resolution respirometry was used with intact and permeabilized cells. To reveal potential mechanistic targets by which HFD-induced obesity dysregulates B cell mitochondria, we conducted proteomic analyses and 3D serial block face scanning electron microscopy (SBFEM). High-resolution respirometry revealed that intact LPS-stimulated B cells of obese mice, relative to controls, displayed lower ATP-linked, as well as maximal uncoupled, respiration. To directly investigate mitochondrial function, we used permeabilized LPS-stimulated B cells, which displayed increased H2O2 emission and production with obesity. We also examined oxidative phosphorylation efficiency simultaneously, which revealed that oxygen consumption and ATP production were decreased in LPS-stimulated B cells with obesity relative to controls. Despite minimal changes in total respiratory complex abundance, in LPS-stimulated B cells of obese mice, three of the top ten most downregulated proteins were all accessory subunits of respiratory complex I. SBFEM showed that B cells of obese mice, compared to controls, underwent no change in mitochondrial cristae integrity but displayed increased mitochondrial volume that was linked to bioenergetic function. Collectively, these results establish a proof of concept that HFD-induced obesity dysregulates the mitochondrial bioenergetic metabolism of activated splenic B cells.

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Section: Discussionmentioning

confidence: 96%

High Fat Diet-Induced Obesity Dysregulates Splenic B Cell Mitochondrial Activity

Pal,

Lin,

Boykov

et al. 2023

Nutrients

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“…It was recently demonstrated that phenotypic and functional features of B cells from two different human subcutaneous adipose depots may differ significantly [ 224 ]. Analyses of the B cells from the breast and abdominal subcutaneous AT revealed that in obese women, B cells from the abdominal AT are “more inflammatory” than those from the breast.…”

Section: Inflammatory Response and Ir (See Also The Summary In ...mentioning

confidence: 99%

Molecular Mechanisms for the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity

Szukiewicz

2023

IJMS

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The comprehensive anabolic effects of insulin throughout the body, in addition to the control of glycemia, include ensuring lipid homeostasis and anti-inflammatory modulation, especially in adipose tissue (AT). The prevalence of obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, has been increasing worldwide on a pandemic scale with accompanying syndemic health problems, including glucose intolerance, insulin resistance (IR), and diabetes. Impaired tissue sensitivity to insulin or IR paradoxically leads to diseases with an inflammatory component despite hyperinsulinemia. Therefore, an excess of visceral AT in obesity initiates chronic low-grade inflammatory conditions that interfere with insulin signaling via insulin receptors (INSRs). Moreover, in response to IR, hyperglycemia itself stimulates a primarily defensive inflammatory response associated with the subsequent release of numerous inflammatory cytokines and a real threat of organ function deterioration. In this review, all components of this vicious cycle are characterized with particular emphasis on the interplay between insulin signaling and both the innate and adaptive immune responses related to obesity. Increased visceral AT accumulation in obesity should be considered the main environmental factor responsible for the disruption in the epigenetic regulatory mechanisms in the immune system, resulting in autoimmunity and inflammation.

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“…It was recently demonstrated that phenotypic and functional features of B cells from two different human subcutaneous adipose depots may differ significantly [214]. Analyses of the B cells from the breast and abdominal subcutaneous AT revealed that in obese women, B cells from the abdominal AT are "more inflammatory" than those from the breast.…”

Section: B Cellsmentioning

confidence: 99%

Molecular Mechanisms of the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity

Szukiewicz¹

2023

Preprint

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The comprehensive anabolic effects of insulin throughout the body, in addition to the control of glycemia, also include ensuring lipid homeostasis and anti-inflammatory modulation, especially in adipose tissue (AT). The prevalence of obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, has been increasing worldwide on a pandemic scale with accompanying syndemic health problems, including glucose intolerance, insulin resistance (IR) and diabetes. Impaired tissue sensitivity to insulin or IR paradoxically leads to diseases with an inflammatory component despite hyperinsulinemia. Therefore, an excess of visceral AT in obesity initiates chronic low-grade inflammatory conditions that interfere with insulin signaling via insulin receptor (INSR). Moreover, in response to IR, hyperglycemia itself stimulates a primarily defensive inflammatory response associated with the subsequent release of numerous inflammatory cytokines and a real threat of organ function deterioration. In this review, all components of this vicious cycle are characterized with particular emphasis on the interplay between insulin signaling and both the innate and adaptive immune responses related to obesity. Increased visceral AT accumulation in obesity should be considered the main environmental factor responsible for the disruption in the epigenetic regulatory mechanisms in the immune system, resulting in autoimmunity and inflammation.

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Phenotypic and functional features of B cells from two different human subcutaneous adipose depots

Cited by 7 publications

References 76 publications

High Fat Diet-Induced Obesity Dysregulates Splenic B Cell Mitochondrial Activity

High Fat Diet-Induced Obesity Dysregulates Splenic B Cell Mitochondrial Activity

Molecular Mechanisms for the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity

Molecular Mechanisms of the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity

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