Abscisic acid enhances glucose disposal and induces brown fat activity in adipocytes in vitro and in vivo

Sturla, Laura; Mannino, Elena; Scarfı̀, Sonia; Bruzzone, Santina; Magnone, Mirko; Sociali, Giovanna; Booz, Valeria; Guida, Lucrezia; Vigliarolo, Tiziana; Fresia, Chiara; Emionite, Laura; Buschiazzo, Ambra; Marini, Cecilia; Sambuceti, Gianmario; Flora, Antonio De; Zocchi, Elena

doi:10.1016/j.bbalip.2016.11.005

Cited by 32 publications

(45 citation statements)

References 60 publications

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“…Further hLanCL2 acts as a positive regulator within the Akt/mTORC2 pathway by enabling the insulin-dependent phosphorylation of Akt via an interaction with the mTORC2-complex, thereby contributing to cell survival [61]. Due to the role of ABA in inflammatory diseases and diabetes, hLanCL2 is currently considered a promising therapeutic target [62–64]. …”

Section: Discussionmentioning

confidence: 99%

A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum

et al. 2018

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The complex life-cycle of the human malaria parasite Plasmodium falciparum requires a high degree of tight coordination allowing the parasite to adapt to changing environments. One of the major challenges for the parasite is the human-to-mosquito transmission, which starts with the differentiation of blood stage parasites into the transmissible gametocytes, followed by the rapid conversion of the gametocytes into gametes, once they are taken up by the blood-feeding Anopheles vector. In order to pre-adapt to this change of host, the gametocytes store transcripts in stress granules that encode proteins needed for parasite development in the mosquito. Here we report on a novel stress granule component, the seven-helix protein 7-Helix-1. The protein, a homolog of the human stress response regulator LanC-like 2, accumulates in stress granules of female gametocytes and interacts with ribonucleoproteins, such as CITH, DOZI, and PABP1. Malaria parasites lacking 7-Helix-1 are significantly impaired in female gametogenesis and thus transmission to the mosquito. Lack of 7-Helix-1 further leads to a deregulation of components required for protein synthesis. Consistently, inhibitors of translation could mimic the 7-Helix-1 loss-of-function phenotype. 7-Helix-1 forms a complex with the RNA-binding protein Puf2, a translational regulator of the female-specific antigen Pfs25, as well as with pfs25-coding mRNA. In accord, gametocytes deficient of 7-Helix-1 exhibit impaired Pfs25 synthesis. Our data demonstrate that 7-Helix-1 constitutes stress granules crucial for regulating the synthesis of proteins needed for life-cycle progression of Plasmodium in the mosquito vector.

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Section: Discussionmentioning

confidence: 99%

A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum

et al. 2018

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“…Interestingly, ABA worsened the inflammation in models of IBD when PPARγ was absent from T cells (Guri et al, 2011; Viladomiu et al, 2013), indicating that ABA indeed plays a dual role and acts both pro- and anti-inflammatory. Apart from its inflammation-modulating functions, ABA signals via LANCL2 have also been linked to metabolic reprogramming of adipocytes into brown fat cells (Sturla et al, 2017), which can be especially beneficial in the context of diabetes where a dual direct effect on immune cells and metabolism could contribute to reduced inflammation (Ray et al, 2016). One possible mechanism for the metabolic reprogramming is an effect of LANCL2 on the Akt/mTORC2 pathway, where LANCL2 influences insulin-dependent Akt phosphorylation (Zeng et al, 2014).…”

Section: Physiological and Pharmacological Effects Of Aba In Animalsmentioning

confidence: 99%

Abscisic Acid as Pathogen Effector and Immune Regulator

et al. 2017

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Abscisic acid (ABA) is a sesquiterpene signaling molecule produced in all kingdoms of life. To date, the best known functions of ABA are derived from its role as a major phytohormone in plant abiotic stress resistance. Different organisms have developed different biosynthesis and signal transduction pathways related to ABA. Despite this, there are also intriguing common themes where ABA often suppresses host immune responses and is utilized by pathogens as an effector molecule. ABA also seems to play an important role in compatible mutualistic interactions such as mycorrhiza and rhizosphere bacteria with plants, and possibly also the animal gut microbiome. The frequent use of ABA in inter-species communication could be a possible reason for the wide distribution and re-invention of ABA as a signaling molecule in different organisms. In humans and animal models, it has been shown that ABA treatment or nutrient-derived ABA is beneficial in inflammatory diseases like colitis and type 2 diabetes, which confer potential to ABA as an interesting nutraceutical or pharmacognostic drug. The anti-inflammatory activity, cellular metabolic reprogramming, and other beneficial physiological and psychological effects of ABA treatment in humans and animal models has sparked an interest in this molecule and its signaling pathway as a novel pharmacological target. In contrast to plants, however, very little is known about the ABA biosynthesis and signaling in other organisms. Genes, tools and knowledge about ABA from plant sciences and studies of phytopathogenic fungi might benefit biomedical studies on the physiological role of endogenously generated ABA in humans.

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“…Later, by the use of LY294002, a PI3K specific inhibitor, the PI3K/Akt signaling pathway was demonstrated to mediate the ABA-induced activation of NADPH oxidase and of ROS generation, in the murine macrophage cell line RAW264.7 (11) and of glucose transport in rodent 3T3-L1 adipocytes (80). More recently, Zeng et al (62) demonstrated that LANCL2 positively regulates Akt phosphorylation in four different liver cell lines.…”

Section: Lancl2 Signaling Pathwaymentioning

confidence: 99%

Abscisic Acid: A Novel Nutraceutical for Glycemic Control

et al. 2017

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Abscisic acid is naturally present in fruits and vegetables, and it plays an important role in managing glucose homeostasis in humans. According to the latest U.S. dietary survey, about 92% of the population might have a deficient intake of ABA due to their deficient intake of fruits and vegetables. This review summarizes the in vitro, preclinical, mechanistic, and human translational findings obtained over the past 15 years in the study of the role of ABA in glycemic control. In 2007, dietary ABA was first reported to ameliorate glucose tolerance and obesity-related inflammation in mice. The most recent findings regarding the topic of ABA and its proposed receptor lanthionine synthetase C-like 2 in glycemic control and their interplay with insulin and glucagon-like peptide-1 suggest a major role for ABA in the physiological response to a glucose load in humans. Moreover, emerging evidence suggests that the ABA response might be dysfunctional in diabetic subjects. Follow on intervention studies in healthy individuals show that low-dose dietary ABA administration exerts a beneficial effect on the glycemia and insulinemia profiles after oral glucose load. These recent findings showing benefits in humans, together with extensive efficacy data in mouse models of diabetes and inflammatory disease, suggest the need for reference ABA values and its possible exploitation of the glycemia-lowering effects of ABA for preventative purposes. Larger clinical studies on healthy, prediabetic, and diabetic subjects are needed to determine whether addressing the widespread dietary ABA deficiency improves glucose control in humans.

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Abscisic acid enhances glucose disposal and induces brown fat activity in adipocytes in vitro and in vivo

Cited by 32 publications

References 60 publications

A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum

A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum

Abscisic Acid as Pathogen Effector and Immune Regulator

Abscisic Acid: A Novel Nutraceutical for Glycemic Control

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