Estrogen enhances browning in adipose tissue by M2 macrophage polarization via heme oxygenase‐1

Sul, Ok-Joo; Hyun, Hyo-Jung; Rajasekaran, Monisha; Suh, Jae-Hee; Choi, Hye‐Seon

doi:10.1002/jcp.29971

Cited by 13 publications

(9 citation statements)

References 45 publications

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“…5), this nding is in line with our previous literature [7]. Sul et al further indicated exogenous administration of E 2 enhanced browning in vivo and invitro, which might result from the anti-oxidant activity of E 2 [26]. ALA supplementation increased the serum levels of irisin, suggesting the browning effects of ALA is partly mediated via irisin production.…”

Section: Discussionsupporting

confidence: 90%

AMP-activated protein kinase (AMPK) contributes to the anti-obesity effects and adipose tissue browning of alpha-lipoic acid in ovariectomized rats

Shen

Chung

Huang

et al. 2021

Preprint

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BackgroundBilateral ovariectomy is an experimental model used to analyze the conditions of menopause and develop strategies for alleviation of the deleterious effects during estrogen deficiency. Brown and beige adipocytes exert thermogenesis capacities and are promising therapeutic strategy for obesity. This study aims to investigate the adipose tissue browning potentials of antioxidant α-lipoic acid (ALA) and underlying mechanisms involved in ovariectomized (Ovx) rats.Methods:Eight weeks old female Wistar rats were randomly divided into Sham or Ovx groups. The Ovx rats were subjected to bilateral ovariectomy and administered with ALA 200 or ALA 300 mg/kg/day (gavage) for 8 weeks. Results:Ovx group significantly increased boy weight (BW) and fat pad mass as compared to Sham group, while ALA supplementation reversed these changes. Lipid profiles including serum triglycerides (TG), total (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated in the Ovx group, whereas the ALA treatment showed a significant decrease in these levels. Furthermore, high density lipoprotein cholesterol (HDL-C) and myokine irisin secretion were increased by ALA as well. Morphology results showed ALA treatment reduced Ovx-induced adipocyte hypertrophy and enhanced UCP1 expression by immunohistochemical staining in inguinal WAT. Protein expression of brown fat-specific markers UCP1, PRDM16 and CIDEA was markedly reduced in Ovx rats, whereas ALA treatment reversed these changes. ALA significantly increased liver kinase B1 (LKB1) and phosphorylation of AMP-activated protein kinase (AMPK) and the downstream acetyl-CoA carboxylase (ACC) that were decreased by Ovx, suggesting the browning effects were mediated by AMPK signaling. Conclusions:ALA ameliorates obesity caused by hormone deprivation in menopause via conversion of white to beige adipocytes concomitant with the activation of AMPK signaling.

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Section: Discussionsupporting

confidence: 90%

AMP-activated protein kinase (AMPK) contributes to the anti-obesity effects and adipose tissue browning of alpha-lipoic acid in ovariectomized rats

Shen

Chung

Huang

et al. 2021

Preprint

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show abstract

“…For example, loss of estrogens by ovariectomizing reduced WAT expression of glutathione peroxidase 3 ( Gpx3) ( 41 ), a gene important for the protection of cells from oxidative stress in the form of reactive oxygen species (ROS) ( 78 ). Furthermore, E2 reduced ROS levels and enhanced browning in female mouse SAT through promoting macrophage heme oxygenase-1 ( Hmox1 , also known as HO-1 ) expression ( 79 ). Similarly, E2 treatment of 3T3-L1 adipocytes increased expression of genes encoding the ROS reducing antioxidants HO-1, NAD(P)H:quinone oxidoreductase 1 ( NQO1 ) and glutamate-cysteine ligase ( GCL ), directly in the adipocytes ( 80 ).…”

Section: Mechanisms Of Action and Metabolic Regulation By Estrogen In...mentioning

confidence: 99%

Metabolic and Epigenetic Regulation by Estrogen in Adipocytes

et al. 2022

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Sex hormones contribute to differences between males and females in body fat distribution and associated disease risk. Higher concentrations of estrogens are associated with a more gynoid body shape and with more fat storage on hips and thighs rather than in visceral depots. Estrogen-mediated protection against visceral adiposity is shown in post-menopausal women with lower levels of estrogens and the reduction in central body fat observed after treatment with hormone-replacement therapy. Estrogen exerts its physiological effects via the estrogen receptors (ERα, ERβ and GPR30) in target cells, including adipocytes. Studies in mice indicate that estrogen protects against adipose inflammation and fibrosis also before the onset of obesity. The mechanisms involved in estrogen-dependent body fat distribution are incompletely understood, but involve, e.g., increased mTOR signaling and suppression of autophagy and adipogenesis/lipid storage. Estrogen plays a key role in epigenetic regulation of adipogenic genes by interacting with enzymes that remodel DNA methylation and histone tail post-translational modifications. However, more studies are needed to map the differential epigenetic effects of ER in different adipocyte subtypes, including those in subcutaneous and visceral adipose tissues. We here review recent discoveries of ER-mediated transcriptional and epigenetic regulation in adipocytes, which may explain sexual dimorphisms in body fat distribution and obesity-related disease risk.

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“…The cardiac HO-1 expression and activity are reduced in response to ovariectomy [ 57 ]. E 2 increases HO-1 expression in aorta [ 58 ], prostatic stoma [ 59 ], endothelial progenitor cells [ 60 ], and macrophages [ 61 ], leading to decreased reactive oxygen species (ROS) levels. In addition, E 2 inhibits the endothelin-induced inhibition of HO-1 expression in cardiomyoblasts [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Does G Protein-Coupled Estrogen Receptor 1 Contribute to Cisplatin-Induced Acute Kidney Injury in Male Mice?

Gohar

Almutlaq

Fan

et al. 2022

IJMS

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Nephrotoxicity is the dose-limiting side-effect of the chemotherapeutic agent cisplatin (Cp). Recent evidence points to renal protective actions of G protein-coupled estrogen receptor 1 (GPER1). In addition, it has been shown that GPER1 signaling elicits protective actions against acute ischemic injuries that involve multiple organ systems; however, the involvement of GPER1 signaling in Cp-induced acute kidney injury (AKI) remains unclear. This study tested whether genetic deletion of GPER1 exacerbates Cp-induced AKI in male mice. We subjected male mice, homozygous (homo) and heterozygous (het) knockout for the GPER1 gene, and wild-type (WT) littermates to Cp or saline injections and assessed markers for renal injury on the third day after injections. We also determined serum levels of proinflammatory markers in saline and Cp-treated mice. Given the protective role of heme oxygenase-1 (HO-1) in Cp-mediated apoptosis, we also investigated genotypic differences in renal HO-1 abundance, cell death, and proliferation by Western blotting, the TUNEL assay, and Ki67 immunostaining, respectively. Cp increased serum creatinine, urea, and neutrophil gelatinase-associated lipocalin (NGAL) levels, the renal abundance of kidney injury molecule-1, and NGAL in all groups. Cp-induced AKI resulted in comparable histological evidence of injury in all genotypes. WT and homo mice showed greater renal HO-1 abundance in response to Cp. Renal HO-1 abundance was lower in Cp-treated homo, compared to Cp-treated WT mice. Of note, GPER1 deletion elicited a remarkable increase in renal apoptosis; however, no genotypic differences in cell proliferation were observed. Cp augmented kidney Ki67-positive counts, regardless of the genotype. Overall, our data do not support a role for GPER1 in mediating Cp-induced renal injury. GPER1 deletion promotes renal apoptosis and diminishes HO-1 induction in response to Cp, suggesting that GPER1 may play cytoprotective and anti-apoptotic actions in AKI. GPER1-induced regulation of HO-1 and apoptosis may offer novel therapeutic targets for the treatment of AKI.

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Estrogen enhances browning in adipose tissue by M2 macrophage polarization via heme oxygenase‐1

Cited by 13 publications

References 45 publications

AMP-activated protein kinase (AMPK) contributes to the anti-obesity effects and adipose tissue browning of alpha-lipoic acid in ovariectomized rats

AMP-activated protein kinase (AMPK) contributes to the anti-obesity effects and adipose tissue browning of alpha-lipoic acid in ovariectomized rats

Metabolic and Epigenetic Regulation by Estrogen in Adipocytes

Does G Protein-Coupled Estrogen Receptor 1 Contribute to Cisplatin-Induced Acute Kidney Injury in Male Mice?

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