Loss of PPARγ in immune cells impairs the ability of abscisic acid to improve insulin sensitivity by suppressing monocyte chemoattractant protein-1 expression and macrophage infiltration into white adipose tissue

Guri, Amir J.; Hontecillas, Raquel; Ferrer, Gerardo; Casagran, Oriol; Wankhade, Umesh D.; Noble, Alexis M; Eizirik, Décio L.; Ortis, Fernanda; Cnop, Miriam; Liu, Dongmin; Si, Hongwei; Bassaganya‐Riera, Josep

doi:10.1016/j.jnutbio.2007.02.010

Cited by 83 publications

(99 citation statements)

References 37 publications

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“…Moreover, incubation with ABA (0.01-100 M) for 6 h consistently increased MCP-1 release from human monocytes (data not shown). The fact that stromal vascular cells extracted from murine white adipose tissue are a mixed cell population, comprising macrophages, pre-adipocytes, T lymphocytes, and endothelial cells, may account for the discrepancy between our observation and the report by Guri et al (49). Indeed, ABA-induced transactivation of peroxisome proliferator-activated receptor ␥ in a purified cell system in vitro is reported by the authors on pre-adipocytes (48).…”

contrasting

confidence: 98%

“…6), possibly leading to the recruitment and activation of further monocytes to the site of the initial endothelial lesion. Recently, dietary ABA has been reported as follows: (i) to improve glucose tolerance in obese mice (48), and (ii) to induce an increased expression of peroxisome proliferatoractivated receptor ␥ and a reduced MCP-1 expression in stromal vascular cells isolated from murine white adipose tissue (49). The first observation is in agreement with the recent demonstration that ABA stimulates insulin release from murine and human pancreatic islets (50).…”

supporting

confidence: 71%

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Abscisic Acid Released by Human Monocytes Activates Monocytes and Vascular Smooth Muscle Cell Responses Involved in Atherogenesis

Magnone

Bruzzone²,

Guida³

et al. 2009

Journal of Biological Chemistry

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Abscisic acid (ABA) is a phytohormone recently identified as a new endogenous pro-inflammatory hormone in human granulocytes. Here we report the functional activation of human monocytes and vascular smooth muscle cells by ABA. Incubation of monocytes with ABA evokes an intracellular Ca 2؉ rise through the second messenger cyclic ADP-ribose, leading to NF-B activation and consequent increase of cyclooxygenase-2 expression and prostaglandin E 2 production and enhanced release of MCP-1 (monocyte chemoattractant protein-1) and of metalloprotease-9, all events reportedly involved in atherogenesis. Moreover, monocytes release ABA when exposed to thrombin-activated platelets, a condition occurring at the injured vascular endothelium; monocyte-derived ABA behaves as an autocrine and paracrine pro-inflammatory hormone-stimulating monocyte migration and MCP-1 release, as well as vascular smooth muscle cells migration and proliferation. These results, and the presence of ABA in human arterial plaques at a 10-fold higher concentration compared with normal arterial tissue, identify ABA as a new signal molecule involved in the development of atherosclerosis and suggest a possible new target for anti-atherosclerotic therapy. ABA2 is an isoprenoid phytohormone regulating several physiological functions in Metaphyta, including response to abiotic stress (1), and in lower Metazoa, where ABA mediates temperature-induced oxygen consumption and water filtration in sponges (2) Monocytes play a key role in both inflammation and immunity by performing antigen presentation, phagocytosis, and immunomodulation through the production of various cytokines and growth factors (6). In atherosclerosis, a chronic immune inflammatory disease, the interaction between monocytes, platelets, and injured luminal endothelium is a crucial event leading to the atherosclerotic lesion of the arterial intima (7,8). Platelets trigger atherogenesis through adhesion to damaged endothelial cells and release of pro-inflammatory mediators, recruiting circulating monocytes to the site of the lesion (9). Monocytes attach to and penetrate the vessel wall, where they undergo transformation into macrophages and eventually into foam cells (10). At the site of the atherosclerotic lesion, monocytes/macrophages, platelets, and endothelial cells release chemoattractants, growth factors, and cytokines, which stimulate VSMC proliferation and migration into the sub-endothelium. Thrombus organization, extracellular matrix synthesis, and VSMC proliferation eventually lead to the development of the atheromatous plaque (7-10). Here we investigate the effect of ABA on human monocytes and VSMC and its possible role in the activation of cell responses known to be responsible for atherogenesis.

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confidence: 98%

supporting

confidence: 71%

Abscisic Acid Released by Human Monocytes Activates Monocytes and Vascular Smooth Muscle Cell Responses Involved in Atherogenesis

Magnone

Bruzzone²,

Guida³

et al. 2009

Journal of Biological Chemistry

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“…ABA induces PPARγ expression and this is required for its beneficial effects in the context of widely different conditions: decreased pathology in models of IBD, enhanced insulin sensitivity, and extended mouse lifespan during influenza infection. 11,32,50 PPARγ is notable in the context of malaria because of its ability to limit inflammation-based pathology while also increasing pathogen clearance. In particular, enhanced PPARγ activity has been shown to increase CD36-mediated phagocytosis of P. falciparum-infected RBCs and the PPARγ agonist rosiglitazone was shown to enhance parasite clearance and reduce inflammation biomarkers in a human trial.…”

Section: Discussionmentioning

confidence: 99%

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

Glennon¹,

Adams²,

Hicks³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Nearly half of the world's population is at risk for malaria. Increasing drug resistance has intensified the need for novel therapeutics, including treatments with intrinsic transmission-blocking properties. In this study, we demonstrate that the isoprenoid abscisic acid (ABA) modulates signaling in the mammalian host to reduce parasitemia and the formation of transmissible gametocytes and in the mosquito host to reduce parasite infection. Oral ABA supplementation in a mouse model of malaria was well tolerated and led to reduced pathology and enhanced gene expression in the liver and spleen consistent with infection recovery. Oral ABA supplementation also increased mouse plasma ABA to levels that can signal in the mosquito midgut upon blood ingestion. Accordingly, we showed that supplementation of a Plasmodium falciparum-infected blood meal with ABA increased expression of mosquito nitric oxide synthase and reduced infection prevalence in a nitric oxide-dependent manner. Identification of the mechanisms whereby ABA reduces parasite growth in mammals and mosquitoes could shed light on the balance of immunity and metabolism across eukaryotes and provide a strong foundation for clinical translation.

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“…Abscisic acid (ABA) 3 is an isoprenoid phytohormone discovered in the early 1960s that has received some recent attention due to its medicinal applications (1). Specifically, oral ABA administration has shown prophylactic and therapeutic efficacy in mouse models of diabetes, inflammatory bowel disease, and atherosclerosis (2)(3)(4)(5)(6).…”

mentioning

confidence: 99%

“…Specifically, oral ABA administration has shown prophylactic and therapeutic efficacy in mouse models of diabetes, inflammatory bowel disease, and atherosclerosis (2)(3)(4)(5)(6). In line with the anti-diabetic effects of ABA, there is evidence that endogenously generated ABA at nanomolar concentrations can act locally and enhance the insulin-secreting ability of pancreatic ␤-cells (7).…”

mentioning

confidence: 99%

Abscisic Acid Regulates Inflammation via Ligand-binding Domain-independent Activation of Peroxisome Proliferator-activated Receptor γ

Bassaganya‐Riera

Guri

et al. 2011

Journal of Biological Chemistry

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121

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Abscisic acid (ABA) has shown efficacy in the treatment of diabetes and inflammation; however, its molecular targets and the mechanisms of action underlying its immunomodulatory effects remain unclear. This study investigates the role of peroxisome proliferator-activated receptor ␥ (PPAR ␥) and lanthionine synthetase C-like 2 (LANCL2) as molecular targets for ABA. We demonstrate that ABA increases PPAR ␥ reporter activity in RAW 264.7 macrophages and increases ppar ␥ expression in vivo, although it does not bind to the ligand-binding domain of PPAR ␥. LANCL2 knockdown studies provide evidence that ABAmediated activation of macrophage PPAR ␥ is dependent on lancl2 expression. Consistent with the association of LANCL2 with G proteins, we provide evidence that ABA increases cAMP accumulation in immune cells. ABA suppresses LPS-induced prostaglandin E 2 and MCP-1 production via a PPAR ␥-dependent mechanism possibly involving activation of PPAR ␥ and suppression of NF-B and nuclear factor of activated T cells. LPS challenge studies in PPAR ␥-expressing and immune cell-specific PPAR ␥ null mice demonstrate that ABA down-regulates toll-like receptor 4 expression in macrophages and T cells in vivo through a PPAR ␥-dependent mechanism. Global transcriptomic profiling and confirmatory quantitative RT-PCR suggest novel candidate targets and demonstrate that ABA treatment mitigates the effect of LPS on the expression of genes involved in inflammation, metabolism, and cell signaling, in part, through PPAR ␥. In conclusion, ABA decreases LPS-mediated inflammation and regulates innate immune responses through a bifurcating pathway involving LANCL2 and an alternative, ligand-binding domain-independent mechanism of PPAR ␥ activation.

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Loss of PPARγ in immune cells impairs the ability of abscisic acid to improve insulin sensitivity by suppressing monocyte chemoattractant protein-1 expression and macrophage infiltration into white adipose tissue

Cited by 83 publications

References 37 publications

Abscisic Acid Released by Human Monocytes Activates Monocytes and Vascular Smooth Muscle Cell Responses Involved in Atherogenesis

Abscisic Acid Released by Human Monocytes Activates Monocytes and Vascular Smooth Muscle Cell Responses Involved in Atherogenesis

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

Abscisic Acid Regulates Inflammation via Ligand-binding Domain-independent Activation of Peroxisome Proliferator-activated Receptor γ

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