Effect of Angiotensin II Type 2 Receptor-Interacting Protein on Adipose Tissue Function via Modulation of Macrophage Polarization

Clinical and experimental evidences pointed to the role of immune cells and inflammatory mediators on the development of diseases in obese patients. Therefore, it is our objective to explore experimental studies that approach the relationship between the different types of inflammatory reaction inside the adipose tissue, particularly the macrophage polarization and the development of obesity complications. Further, we intend to speculate how to translate this knowledge, obtained from experimental studies, to treatments applicable to the human diseases. PubMed database was sought using the terms “obesity”, “macrophage” and “polarization”. After applying the filters “Language - English” and “Species - Animals”, we arrived to 90 references. Sixty-two were excluded for being reviews or not related to the main subject. Results in experimental models of obesity pointed a relevant correlation between the macrophage polarization to a type 1 response (M1) inside white adipose tissue and the development of insulin resistance, diabetes and other complications of obesity. Several articles report strategies to shift to a type 2 phenotype (M2), using drugs or lifestyle changes. How these findings could be translated to new human treatments is still an open question that only well designed researches could answer.

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ErbB4 deletion predisposes to development of metabolic syndrome in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00166.2018 ◽

2018 ◽

Vol 315 (4) ◽

pp. E583-E593 ◽

Cited By ~ 11

Author(s):

Fenghua Zeng ◽

Yinqiu Wang ◽

Lance A. Kloepfer ◽

Suwan Wang ◽

Raymond C. Harris

Keyword(s):

Metabolic Syndrome ◽

Adipose Tissue ◽

Glucose Uptake ◽

Egf Receptor ◽

Macrophage Polarization ◽

Wild Type ◽

M1 Macrophage ◽

Egf Receptor Family ◽

Diabetes And Obesity

ErbB4, a member of the EGF receptor family, plays a variety of roles in physiological and pathological states. Genetic studies have indicated a link between ErbB4 and type 2 diabetes and obesity, but its role in metabolic syndrome (MetS) has not been reported. In the current study we found that mice with ErbB4 deletion developed MetS after 24 wk on a medium-fat diet (MFD), as indicated by development of obesity, dyslipidemia, hepatic steatosis, hyperglycemia, hyperinsulinemia, and insulin resistance, compared with wild-type mice. ErbB4 deletion mice also exhibited increased amounts of subcutaneous and visceral fat, with increased serum leptin levels, compared with wild-type mice, whereas levels of adiponectin were not significantly different. Histologically, severe inflammation, indicated by F4/80 immunostaining and M1 macrophage polarization, was detected in inguinal and epididymal white adipose tissue in ErbB4 deletion mice. ErbB4 expression decreased during 3T3-L1 preadipocyte differentiation. Administration of neuroregulin 4, a specific ligand for ErbB4, to 3T3-L1 adipocytes had no effect on adipogenesis and lipolysis but significantly inhibited lipogenesis, promoted browning, induced GLUT4 redistribution to the cell membrane, and increased glucose uptake. Neuroregulin 4 also significantly increased glucose uptake in adipocytes isolated from wild-type mice, while these effects were significantly decreased in adipocytes isolated from ErbB4 deletion mice. In conclusion, our results indicate that ErbB4 may play an important role in glucose homeostasis and lipogenesis. ErbB4 deficiency-related obesity and adipose tissue inflammation may contribute to the development of MetS.

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Local angiotensin II promotes adipogenic differentiation of human adipose tissue mesenchymal stem cells through type 2 angiotensin receptor

Stem Cell Research ◽

10.1016/j.scr.2017.10.022 ◽

2017 ◽

Vol 25 ◽

pp. 115-122 ◽

Cited By ~ 11

Author(s):

Veronika Y. Sysoeva ◽

Liudmila V. Ageeva ◽

Pyotr A. Tyurin-Kuzmin ◽

George V. Sharonov ◽

Daniyar T. Dyikanov ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Angiotensin Ii ◽

Adipogenic Differentiation ◽

Human Adipose Tissue ◽

Angiotensin Receptor

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Angiotensin II type 2 receptor-interacting protein prevents vascular senescence

Journal of the American Society of Hypertension ◽

10.1016/j.jash.2012.01.006 ◽

2012 ◽

Vol 6 (3) ◽

pp. 179-184 ◽

Cited By ~ 13

Author(s):

Li-Juan Min ◽

Masaki Mogi ◽

Jun Iwanami ◽

Fei Jing ◽

Kana Tsukuda ◽

...

Keyword(s):

Angiotensin Ii ◽

Interacting Protein ◽

Vascular Senescence

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Deficiency of Angiotensin Type 2 Receptor Rescues Obesity But Not Hypertension Induced by Overexpression of Angiotensinogen in Adipose Tissue

Endocrinology ◽

10.1210/en.2008-1120 ◽

2008 ◽

Vol 150 (3) ◽

pp. 1421-1428 ◽

Cited By ~ 51

Author(s):

Laurent Yvan-Charvet ◽

Florence Massiéra ◽

Noël Lamandé ◽

Gérard Ailhaud ◽

Michèle Teboul ◽

...

Keyword(s):

Blood Pressure ◽

Adipose Tissue ◽

Angiotensin Ii ◽

Fat Mass ◽

Lipogenic Gene Expression ◽

Angiotensin Type 2 Receptor ◽

Adipocyte Hypertrophy ◽

Angiotensin Type

Increased angiotensinogen (AGT) production by white adipose tissue has been related to not only obesity but also hypertension. Several studies have highlighted the importance of the angiotensin II type 2 receptor (AT2) in the regulation of blood pressure and fat mass, but the relevance of this transporter in a physiopathological model of increased AGT production, as it occurs in obesity, has not yet been investigated. We used transgenic mice that display either a deletion of AT2 (AT2 KO), an overexpression of AGT (OVEX), or both compound mutants (KOVEX). Results demonstrated that adipocyte hypertrophy and increased lipogenic gene expression induced by adipose AGT overproduction was rescued by deletion of AT2. In line with AGT overexpression, KOVEX and OVEX mice have similar increased plasma AGT levels. However, KOVEX mice display a higher blood pressure than OVEX mice. In kidney, renin expression was clearly reduced in OVEX mice, and its expression was normalized in KOVEX mice. Taken together, we demonstrated that the loss of AT2 expression was sufficient to rescue obesity induced by adipose tissue AGT overexpression and confirmed the necessary role of AT2 for the onset of obesity in this model. Furthermore, despite a reduction of adipose mass in KOVEX, AT2 deficiency caused increased renin production, further worsening the hypertension caused by AGT overexpression. Angiotensin type 2 receptor shows antihypertensive function but promotes the angiotensin II-mediated fat mass enlargement.

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