Isoform and tissue dependent impact of apolipoprotein E on adipose tissue metabolic activation: The role of apolipoprotein A1

Background: Estrogen receptor β (ERβ) plays an important role in human metabolism and some of its metabolic actions are mediated by a positive “cross-talk” with Nuclear Factor of Activated T cells (NFAT) and the key metabolic transcriptional coregulator Transcriptional Intermediary Factor 2 (TIF2). Introduction: Our study is an “in situ” morphological evaluation of the communication between ERβ, NFAT and TIF2 in morbid obesity. Potential correlations with clinicopathological parameters and with the presence of diabetes and non-alcoholic fatty liver disease (NAFLD) were also explored. The aim of the present study was to determine the role of ERβ and NFAT in the underlying pathophysiology of obesity and related comorbidities. We have investigated the expression of specific proteins using immunochemistry methodologies. Methods: Our population consists of 50 morbidly obese patients undergoing planned bariatric surgery, during which biopsies were taken from visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and liver and the differential protein expression was evaluated by immunohistochemistry. Results: We demonstrated an extensive intra- and inter-tissue co-expression network, which confirms the tissue-specific and integral role of each one of the investigated proteins in morbid obesity. Moreover, a beneficial role of ERβ and NFATc1 against NAFLD is implicated, whereas the distinct roles of TIF2 still remain an enigma. Conclusions: We believe that our findings will shed light on the complex underlying mechanisms and that the investigated biomarkers could represent future targets for the prevention and therapy of obesity and its comorbidities.

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Transglutaminases and Obesity in Humans: Association of F13A1 to Adipocyte Hypertrophy and Adipose Tissue Immune Response

International Journal of Molecular Sciences ◽

10.3390/ijms21218289 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8289

Author(s):

Mari T. Kaartinen ◽

Mansi Arora ◽

Sini Heinonen ◽

Aila Rissanen ◽

Jaakko Kaprio ◽

...

Keyword(s):

Immune Response ◽

Adipose Tissue ◽

Family Members ◽

Enrichment Analysis ◽

Human Adipose Tissue ◽

Adipocyte Size ◽

Gene Enrichment ◽

Adipocyte Hypertrophy ◽

Mz Twins

Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of TGM family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy–lean twin pairs. We report that F13A1 is the only TGM family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte F13A1 to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of F13A1 to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of F13A1 (ΔHeavy–Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of F13A1 in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation.

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Dihydrotanshinone I Attenuates Plaque Vulnerability in Apolipoprotein E-Deficient Mice: Role of Receptor-Interacting Protein 3

Antioxidants and Redox Signaling ◽

10.1089/ars.2019.7796 ◽

2020 ◽

Author(s):

Wenwen Zhao ◽

Chunxia Li ◽

Hao Zhang ◽

Qihui Zhou ◽

Xuehong Chen ◽

...

Keyword(s):

Apolipoprotein E ◽

Plaque Vulnerability ◽

Interacting Protein ◽

Deficient Mice

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Adipose Tissue Immunomodulation and Treg/Th17 Imbalance in the Impaired Glucose Metabolism of Children with Obesity

Children ◽

10.3390/children8070554 ◽

2021 ◽

Vol 8 (7) ◽

pp. 554

Author(s):

Stefania Croce ◽

Maria Antonietta Avanzini ◽

Corrado Regalbuto ◽

Erika Cordaro ◽

Federica Vinci ◽

...

Keyword(s):

Adipose Tissue ◽

Glucose Metabolism ◽

Th17 Cells ◽

Metabolic Disorders ◽

Potential Role ◽

Immune Monitoring ◽

Metabolic Dysfunction ◽

Impaired Glucose Metabolism ◽

T Cell Infiltration

In the last few decades, obesity has increased dramatically in pediatric patients. Obesity is a chronic disease correlated with systemic inflammation, characterized by the presence of CD4 and CD8 T cell infiltration and modified immune response, which contributes to the development of obesity related diseases and metabolic disorders, including impaired glucose metabolism. In particular, Treg and Th17 cells are dynamically balanced under healthy conditions, but imbalance occurs in inflammatory and pathological states, such as obesity. Some studies demonstrated that peripheral Treg and Th17 cells exhibit increased imbalance with worsening of glucose metabolic dysfunction, already in children with obesity. In this review, we considered the role of adipose tissue immunomodulation and the potential role played by Treg/T17 imbalance on the impaired glucose metabolism in pediatric obesity. In the patient care, immune monitoring could play an important role to define preventive strategies of pediatric metabolic disease treatments.

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An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity

International Journal of Molecular Sciences ◽

10.3390/ijms22157975 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7975

Author(s):

Saioa Gómez-Zorita ◽

Iñaki Milton-Laskibar ◽

Laura García-Arellano ◽

Marcela González ◽

María P. Portillo

Keyword(s):

Adipose Tissue ◽

Protective Role ◽

Inflammatory Factors ◽

Current Evidence ◽

Disease Outcomes ◽

Lower Activation ◽

Two Factors ◽

Obese Subjects ◽

Ace2 Gene

The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.

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