HO-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, and Isoprostane Levels in Mice Fed High Fructose Diets

Khitan, Zeid; Harsh, Mohit; Sodhi, Komal; Shapiro, Joseph I.; Abraham, Nader G.

doi:10.1155/2014/980547

Cited by 31 publications

(45 citation statements)

References 59 publications

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“…Treatment with SnMP tended to increase the levels of HO-1 mRNA and protein under all conditions, reaching significance for HO-1 in control and hemin treated cells (Fig 3.5b & c). This effect is consistent with other reports [214,243] and demonstrates the efficacy of the SnMP treatment. Similar results were observed for NQO1 and GCLM (Fig 3.5d & e).…”

Section: Co-treatment With a Ho-1 Inhibitor (Snmp) Does Not Prevent Tsupporting

confidence: 93%

“…HO-1 induction remodels adipocytes, resulting in hyperplasia instead of hypertrophy. These adipocytes increase the production of AMPK, PPARγ, and adiponectin, at the same time decreasing the production of inflammatory markers and cytokines [209,210,215,243].…”

Section: Ho-1 and Adipocytesmentioning

confidence: 99%

“…To investigate whether the inhibitory effects of CoPP and hemin were associated with increased HO-1 activity we performed a series of experiments in the presence or absence of SnMP, a widely used inhibitor of HO-1 activity [243,294]. Treatment of cells with SnMP (5 µM) had no obvious effect on lipid accumulation in control cells or in cells treated with CoPP (0.25 µM) or hemin (3 µM) (Fig 3.5a).…”

Section: Co-treatment With a Ho-1 Inhibitor (Snmp) Does Not Prevent Tmentioning

confidence: 99%

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Characterisation of the relationship between Heme-oxygenase-1 and adiponectin

Yang¹

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The prevalence of obesity is growing at an alarming rate worldwide, and current therapies have limited benefits. Therefore, it is essential to increase our understanding of the underlying mechanisms so that new strategies can be developed to reduce the incidence of obesity related diseases. Adiponectin is an adipocyte-derived hormone that regulates glucose and lipid metabolism via direct and indirect mechanisms and has anti-inflammatory, anti-diabetic, anti-atherogenic and cardioprotective properties. Hypoadiponectinemia is implicated in the aetiology of obesity-related diseases making strategies to increase circulating adiponectin levels therapeutically attractive.Emerging evidence, predominantly from preclinical studies, suggests induction of heme-oxygenase-1 (HO-1) increases adiponectin production concomitant with decreased inflammatory tone prompting the proposal of a "HO-1 -adiponectin axis." However, the underlying mechanisms of increased adiponectin production via HO-1 induction are poorly defined; indeed a direct relationship has not been demonstrated. Thus, the overarching aim of this thesis is to investigate the effects of HO-1 induction on adiponectin production as well as adipocyte and adipose tissue remodelling and metabolic parameters using cellular and mouse models.Initial studies were designed to characterize the direct effect of HO-1 induction on adiponectin production. We found that treatment with the widely used HO-1 inducer cobalt protoporphyrin (CoPP) or hemin for 24-48 h increased HO-1 expression and activity without affecting adiponectin expression and secretion, in human mature adipocyte under a variety of experimental scenarios.Treatment of adipocytes with TNFα reduced adiponectin production and induced pro-inflammatory cytokines production. HO-1 induction failed to reverse these effects. These results do not support a direct HO-1 -adiponectin axis.However, literature suggests that chronic induction of HO-1 via CoPP administration throughout differentiation, promotes adiponectin secretion, albeit in the context of reduced adipogenesis. While our previous findings argued against the existence of a direct "HO-1 -adiponectin axis," they did not address the potential effects of chronic induction of HO-1 on adiponectin production. Thus, we extended our study to characterise the effects of chronic HO-1 induction throughout differentiation of human preadipocytes. In this study we demonstrate that chronic induction of HO-1 with CoPP or hemin throughout differentiation results in dose-dependent inhibition of adipogenesis and adiponectin production as well as induction of additional NRF2 target genes. Co-treatment with SnMP (HO-1 activity inhibitor) and HO-1 siRNA did not prevent these effects. These findings suggest that the chronic treatment with CoPP or hemin inhibits adipogenesis and adiponectin production potentially by a HO-1-independent mechanism that may be downstream of NRF2.iii However, our results contradict the majority of reports in the literature. One possibility is that the ...

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Section: Co-treatment With a Ho-1 Inhibitor (Snmp) Does Not Prevent Tsupporting

confidence: 93%

Section: Ho-1 and Adipocytesmentioning

confidence: 99%

Section: Co-treatment With a Ho-1 Inhibitor (Snmp) Does Not Prevent Tmentioning

confidence: 99%

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Characterisation of the relationship between Heme-oxygenase-1 and adiponectin

Yang¹

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“…During hypoxia mediated oxidative stress, cellular heme is released and contributes to the growing "free heme pool. " Free heme is a potent pro-oxidant and increases ROS levels [48]. Elevated levels of heme are toxic and catalyze oxidative damage to cells, tissues, and organs.…”

Section: Gpdh (Mu/mg Protein)mentioning

confidence: 99%

“…Hence the role of HO-1 is vital which acts as the crucial enzyme catalyzing the heme degradation. Khitan and his colleagues [48] stated that the protective effect of HO-1 is ascribed to its role in decreasing the cellular heme content as they are highly toxic and leading to the generation of ROS and RNS. Similarly, in the present study increased HO-1 expression was observed in test adipocytes suggesting that HNE acts as a potent inducer of HO-1 to provide cytoprotective function which was similar to the study reported by Iles and his colleagues [49].…”

Section: Gpdh (Mu/mg Protein)mentioning

confidence: 99%

Hif1α Mediated Ho-1 Expression in Fish Adipocytes: Role of Hypoxia In Ennore Estuary

Perumal¹,

Parasuraman²

2017

J Marine Sci Res Dev

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Heme oxygenase-1 (HO-1), an inducible stress protein; is involved in the regulation of adipogenesis, cellular bioenergetics and cytoprotective mechanism against hypoxia induced oxidative stress. Polluted aquatic environment leads to large oxygen fluctuations which may cause alteration in fish adaptation mechanism by HIF1α regulation. Environmental pollutants have a high tendency to accumulate, persist and bio-concentrate in adipocytes due to its lipophilic nature which ultimately causes adipocytes hypoxia that in turn affects metabolic energy balance. CYP1A2 and HO-1 are the chief detoxifying and cytoprotective enzymes involved in the oxidative metabolism of a wide variety of pollutants and its mediated cytotoxic products. The key role of hypoxia and its mediated signaling protein changes in fish adipocytes due to low dissolved oxygen in Ennore estuary was demonstrated in our previous work. Therefore, we analyzed the effect of pollutants induced hypoxia by assessing CD, HNE, TAC, G3PDH, ATP, HIF1α, HO-1 and CYP1A2 in fish adipocytes of control/unpolluted site and test/polluted site. Increase in CD, HNE, HIF1α, HO-1 along with a decrease in TAC, G3PDH, ATP and CYP1A2 observed in test adipocytes. From the results achieved, it shows that induction of HO-1 by HIF1α is crucial in maintaining the cell integrity to secure adipocytes and its maturation in the fish collected from the hypoxic environment. This study also highlights the role of HIF1α and HO-1 in regulating the expression of CYP1A2 during pollutants induced hypoxic condition.

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Hmox1 promotes osteogenic differentiation at the expense of reduced adipogenic differentiation induced by BMP9 in C3H10T1/2 cells

Liu

et al. 2018

J of Cellular Biochemistry

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Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into a variety of cell types under proper stimuli. Bone morphogenetic protein 9 (BMP9) is able to simultaneously induce both adipogenic and osteogenic differentiation of MSCs although the regulatory molecules involved remain to be fully identified and characterized. Heme oxygenase 1 (Hmox1) plays an essential role not only in fat metabolism, but also in bone development. In the present study, we investigated the functional role of Hmox1 in BMP9-induced osteogenic/adipogenic differentiation in MSCs line C3H10T1/2 and probed the possible mechanism involved. We found that BMP9 promoted the endogenous expression of Hmox1 in C3H10T1/2 cells. Overexpression of Hmox1 or cobalt protoporphyrin (CoPP), an inducer of Hmox1, increased BMP9-induced osteogenic differentiation in vitro. Subcutaneous stem cell implantation in nude mice further confirmed that Hmox1 potentiated BMP9-induced ectopic bone formation in vivo. In contrast, Hmox1 reduced BMP9-induced adipogenic differentiation in C3H10T1/2 cells. Although had no obvious effect on BMP9-induced Smad1/5/8 phosphorylation, Hmox1 enhanced phosphorylation of p38, and AKT, while decreased phosphorylation of ERK1/2. Furthermore, Hmox1 increased total β-catenin protein level, and promoted the nuclear translocation of β-catenin in C3H10T1/2 cells. Taken together, our study strongly suggests that Hmox1 is likely to potentiate osteogenic differentiation and yet decrease adipogenic differentiation induced by BMP9 possibly through regulation of multiple signaling pathways.

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HO-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, and Isoprostane Levels in Mice Fed High Fructose Diets

Cited by 31 publications

References 59 publications

Characterisation of the relationship between Heme-oxygenase-1 and adiponectin

Characterisation of the relationship between Heme-oxygenase-1 and adiponectin

Hif1α Mediated Ho-1 Expression in Fish Adipocytes: Role of Hypoxia In Ennore Estuary

Hmox1 promotes osteogenic differentiation at the expense of reduced adipogenic differentiation induced by BMP9 in C3H10T1/2 cells

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