Oleanolic acid attenuates PCBs-induced adiposity and insulin resistance via HNF1b-mediated regulation of redox and PPARγ signaling

Su, Shan; Wu, Guangyuan; Cheng, Xiaodong; Fan, Junshu; Peng, Jie; Su, Hongfei; Xu, Zhongrui; Cao, Meng; Long, Zi; Hao, Yiming; Li, Ge; Li, Shuang; Hai, Chen; Wang, Xin

doi:10.1016/j.freeradbiomed.2018.06.003

Cited by 44 publications

(28 citation statements)

References 52 publications

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“…3e). HNF1B is known to be an important regulator of glucose and lipid metabolism [32] and expression of the gene is suppressed by palmitate in islets [33,34]. We next focused on studying whether obesity facilitates ROIT downregulation by repressing HNF1B expression.…”

Section: Regulation Of Roit Expression In the Islets Of Obese Mice Bymentioning

confidence: 99%

Obesity-induced reduced expression of the lncRNA ROIT impairs insulin transcription by downregulation of Nkx6.1 methylation

et al. 2020

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Aims/hypothesis Although obesity is a predisposing factor for pancreatic beta cell dysfunction, the mechanisms underlying its negative effect on insulin-secreting cells is still poorly understood. The aim of this study was to identify islet long non-coding RNAs (lncRNAs) involved in obesity-mediated beta cell dysfunction. Methods RNA sequencing was performed to analyse the islets of high-fat diet (HFD)-fed mice and those of normal chow-fed mice (NCD). The function in beta cells of the selected lncRNA 1810019D21Rik (referred to in this paper as ROIT [regulator of insulin transcription]) was assessed after its overexpression or knockdown in MIN6 cells and primary islet cells, as well as in siRNA-treated mice. Then, RNA pull-down, RNA immunoprecipitation, coimmunoprecipitation and bisulphite sequencing were performed to investigate the mechanism of ROIT regulation of islet function.Results ROIT was dramatically downregulated in the islets of the obese mice, as well as in the sera of obese donors with type 2 diabetes, and was suppressed by HNF1B. Overexpression of ROIT in MIN6 cells and islets led to improved glucose homeostasis and insulin transcription. Investigation of the mechanism involved showed that ROIT bound to DNA methyltransferase 3a and caused its degradation through the ubiquitin proteasome pathway, which blocked the methylation of the Nkx6.1 promoter. Conclusions/interpretation These findings functionally suggest a novel link between obesity and beta cell dysfunction via ROIT. Elucidating a precise mechanism for the effect of obesity on lncRNA expression will broaden our understanding of the pathophysiological development of diabetes and facilitate the design of better tools for diabetes prevention and treatment. Data availability The raw RNA sequencing data are available from the NCBI Gene Expression Omnibus (GEO series accession number GSE139991).

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Section: Regulation Of Roit Expression In the Islets Of Obese Mice Bymentioning

confidence: 99%

Obesity-induced reduced expression of the lncRNA ROIT impairs insulin transcription by downregulation of Nkx6.1 methylation

et al. 2020

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“…In fact, the therapeutic potential of oleanolic acid was recently reviewed [108] and from that detailed work it is possible to conclude that indeed this natural compound is a good candidate to become a medicine. Due to this biological potential, the in vivo evaluations are increasing and in the last three years several publications involving the usual activities, such as antitumor [109,110,111], antidiabetic [112,113,114,115], anti-malarial [116] and anti-atherosclerosis [117] or the less common such as its beneficial effect on wound healing and regeneration [118] and the inhibition of matrix metalloproteinase-3 (MMP-3) production [119] have been published. It should be highlighted that this enzyme is involved in the articular cartilage destruction, thus oleanolic acid may be a potential drug to be used in the prevention of osteoarthritis cartilage damage [119].…”

Section: In Vivo Assessments Of Nominated Metabolitesmentioning

confidence: 99%

Scabiosa Genus: A Rich Source of Bioactive Metabolites

et al. 2018

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The genus Scabiosa (family Caprifoliaceae) is considered large (618 scientific plant names of species) although only 62 have accepted Latin binominal names. The majority of the Scabiosa species are widely distributed in the Mediterranean region and some Scabiosa species are used in traditional medicine systems. For instance, Scabiosa columbaria L. is used traditionally against diphtheria while S. comosa Fisch. Ex Roem. and Schult. is used in Mongolian and Tibetan traditional medical settings to treat liver diseases. The richness of Scabiosa species in secondary metabolites such as iridoids, flavonoids and pentacyclic triterpenoids may contribute to its use in folk medicine. Details on the most recent and relevant pharmacological in vivo studies on the bioactive secondary metabolites isolated from Scabiosa species will be summarized and thoroughly discussed.

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“…Su et al [42] administered OA to polychlorinated biphenyls (PCBs)-induced metabolic disfunction mice and observed a significant decrease of FBG, FSI, HOMA-IR, adipocyte size, and serum levels of TG, FFA, and TC. It was also observed a significant decrease of glycemia in the IPGTT and IPITT tests.…”

Section: Resultsmentioning

confidence: 99%

“…A number of authors showed an increase of serum superoxide dismutase (SOD) activity [30,32,37,42,43]. In addition to SOD, Jiang et al [32] and Gamede et al [30] also reported an increase in glutathione peroxidase (GSH-Px) activity.…”

Section: Resultsmentioning

confidence: 99%

Potential Protective Effect of Oleanolic Acid on the Components of Metabolic Syndrome: A Systematic Review

Fernández-Aparicio

Schmidt-RíoValle

Perona

et al. 2019

JCM

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The high prevalence of obesity is a serious public health problem in today’s world. Both obesity and insulin resistance favor the development of metabolic syndrome (MetS), which is associated with a number of pathologies, especially type 2 diabetes mellitus, and cardiovascular diseases. This serious problem highlights the need to search for new natural compounds to be employed in therapeutic and preventive strategies, such as oleanolic acid (OA). This research aimed to systematically review the effects of OA on the main components of MetS as well as oxidative stress in clinical trials and experimental animal studies. Databases searched included PubMed, Medline, Web of Science, Scopus, EMBASE, Cochrane, and CINAHL from 2013 to 2019. Thus, both animal studies (n = 23) and human clinical trials (n = 1) were included in our review to assess the effects of OA formulations on parameters concerning insulin resistance and the MetS components. The methodological quality assessment was performed through using the SYRCLE’s Risk of Bias for animal studies and the Jadad scale. According to the studies in our review, OA improves blood pressure levels, hypertriglyceridemia, hyperglycemia, oxidative stress, and insulin resistance. Although there is scientific evidence that OA has beneficial effects in the prevention and treatment of MetS and insulin resistance, more experimental studies and randomized clinical trials are needed to guarantee its effectiveness.

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Oleanolic acid attenuates PCBs-induced adiposity and insulin resistance via HNF1b-mediated regulation of redox and PPARγ signaling

Cited by 44 publications

References 52 publications

Obesity-induced reduced expression of the lncRNA ROIT impairs insulin transcription by downregulation of Nkx6.1 methylation

Obesity-induced reduced expression of the lncRNA ROIT impairs insulin transcription by downregulation of Nkx6.1 methylation

Scabiosa Genus: A Rich Source of Bioactive Metabolites

Potential Protective Effect of Oleanolic Acid on the Components of Metabolic Syndrome: A Systematic Review

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