Inhibitory effect of PPARγ on NLRP3 inflammasome activation

Yang, Ching Chun; Wu, Chih Hsing; Lin, Tzu Chen; Cheng, Yi; Chang, Chin Sung; Lee, Kuo Ting; Tsai, Pei Jane; Tsai, Yau Sheng

doi:10.7150/thno.46873

Cited by 62 publications

(36 citation statements)

References 73 publications

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“…Conversely, in ob/ob −/− mice, NLRP3 and IL-1β proteins were downregulated. Furthermore, reduced levels of NLRP3 were also observed in ob/ob −/− mouse peritoneal macrophages treated with LPS and nigericin in comparison with wild-type mice ( Yang et al, 2021 ). This certainly underlines the preponderant role of leptin on NLRP3 inflammasome regulation.…”

Section: Discussionmentioning

confidence: 99%

Leptin Signaling in the Ovary of Diet-Induced Obese Mice Regulates Activation of NOD-Like Receptor Protein 3 Inflammasome

Adamowski

Wołodko

Oliveira

et al. 2021

Front. Cell Dev. Biol.

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Obesity leads to ovarian dysfunction and the establishment of local leptin resistance. The aim of our study was to characterize the levels of NOD-like receptor protein 3 (NLRP3) inflammasome activation in ovaries and liver of mice during obesity progression. Furthermore, we tested the putative role of leptin on NLRP3 regulation in those organs. C57BL/6J female mice were treated with equine chorionic gonadotropin (eCG) or human chorionic gonadotropin (hCG) for estrous cycle synchronization and ovary collection. In diet-induced obesity (DIO) protocol, mice were fed chow diet (CD) or high-fat diet (HFD) for 4 or 16 weeks, whereas in the hyperleptinemic model (LEPT), mice were injected with leptin for 16 days (16 L) or saline (16 C). Finally, the genetic obese leptin-deficient ob/ob (+/? and −/−) mice were fed CD for 4 week. Either ovaries and liver were collected, as well as cumulus cells (CCs) after superovulation from DIO and LEPT. The estrus cycle synchronization protocol showed increased protein levels of NLRP3 and interleukin (IL)-18 in diestrus, with this stage used for further sample collections. In DIO, protein expression of NLRP3 inflammasome components was increased in 4 week HFD, but decreased in 16 week HFD. Moreover, NLRP3 and IL-1β were upregulated in 16 L and downregulated in ob/ob. Transcriptome analysis of CC showed common genes between LEPT and 4 week HFD modulating NLRP3 inflammasome. Liver analysis showed NLRP3 protein upregulation after 16 week HFD in DIO, but also its downregulation in ob/ob−/−. We showed the link between leptin signaling and NLRP3 inflammasome activation in the ovary throughout obesity progression in mice, elucidating the molecular mechanisms underpinning ovarian failure in maternal obesity.

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Section: Discussionmentioning

confidence: 99%

Leptin Signaling in the Ovary of Diet-Induced Obese Mice Regulates Activation of NOD-Like Receptor Protein 3 Inflammasome

Adamowski

Wołodko

Oliveira

et al. 2021

Front. Cell Dev. Biol.

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“…This suggests that blocking the functional crosstalk between NF- κ B and NLRP3 may reduce chronic pain induced by bone cancer. Previous studies have shown that rosiglitazone may exert its anti-inflammatory and neuroprotective effects by inhibiting the NLRP3 inflammasome and reducing the expression of NF- κ B [ 26 – 28 ], but whether rosiglitazone can affect NF- κ B and NLRP3 in the spinal cord of rats with BCP to reduce pain needs further exploration.…”

Section: Introductionmentioning

confidence: 99%

Rosiglitazone Alleviates Mechanical Allodynia of Rats with Bone Cancer Pain through the Activation of PPAR-γ to Inhibit the NF-κB/NLRP3 Inflammatory Axis in Spinal Cord Neurons

Zhao

et al. 2021

PPAR Research

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Bone cancer pain (BCP) is a serious clinical problem that affects the quality of life of cancer patients. However, the current treatment methods for this condition are still unsatisfactory. This study investigated whether intrathecal injection of rosiglitazone modulates the noxious behaviors associated with BCP, and the possible mechanisms related to this effect were explored. We found that rosiglitazone treatment relieved bone cancer-induced mechanical hyperalgesia in a dose-dependent manner, promoted the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) in spinal cord neurons, and inhibited the activation of the nuclear factor-kappa B (NF-κB)/nod-like receptor protein 3 (NLRP3) inflammatory axis induced by BCP. However, concurrent administration of the PPAR-γ antagonist GW9662 reversed these effects. The results show that rosiglitazone inhibits the NF-κB/NLRP3 inflammation axis by activating PPAR-γ in spinal neurons, thereby alleviating BCP. Therefore, the PPAR-γ/NF-κB/NLRP3 signaling pathway may be a potential target for the treatment of BCP in the future.

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“…Strikingly, we observed a consistent upregulation of NLRP3 inflammasome genes and accumulation of IL-1β protein in ovaries of leptin treated mice, in opposition to ob/ob -/-mice which evidenced consistent downregulation of NLRP3 and IL-1β proteins. Furthermore, reduced levels of NLRP3 were also observed in ob/ob -/-mouse peritoneal macrophages treated with LPS and nigericin in comparison to wild type mice (Yang et al 2021), what certainly underlines the preponderant role of leptin on NLRP3 inflammasome regulation.…”

Section: Discussionmentioning

confidence: 85%

Leptin Signalling in the Ovary of Diet-Induced Obese Mice Regulates Activation of Nod-Like Receptor Protein 3 Inflammasome

Adamowski

Wołodko

Oliveira

et al. 2021

Preprint

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Obesity leads to ovarian dysfunction and the establishment of local leptin resistance. The aim of our study was to characterise levels of Nod-Like Receptor Protein 3 (NLRP3) inflammasome activation during obesity progression in the mouse ovaries and liver and test the putative role of leptin on its regulation. C57BL/6J mice were treated with equine chorionic gonadotropin (eCG) or human chorionic gonadotropin (hCG) for oestrous cycle synchronisation and ovaries collection. In diet-induced obesity (DIO) model, mice were fed chow diet (CD) or high fat diet (HFD) for 4 or 16 weeks (wk), whereas in hyperleptinemic model (LEPT), mice were injected with leptin for 16 days (16L) or saline (16C) and in the genetic obese leptin-deficient ob/ob (+/? and -/-) animals were fed CD for 4wk. Either ovaries and liver were collected, as well as cumulus cells (CCs) after superovulation from DIO and LEPT. In DIO protocol, protein expression of NLRP3 inflammasome components was increased in 4wk HFD, but decreased in 16wk HFD. Moreover LEPT and ob/ob models revealed NLRP3 and IL-1b; upregulation in 16L and downregulation in ob/ob. Transcriptome analysis of CC showed common genes between LEPT and 4wk HFD modulating NLRP3 inflammasome. Moreover analysis in the liver showed upregulation of NLRP3 protein only after 16wk HFD, but also the downregulation of NLRP3 protein in ob/ob-/-. We showed the link between leptin signalling and NLRP3 inflammasome activation in the ovary throughout obesity progression in mice, elucidating the molecular mechanisms underpinning ovarian failure in maternal obesity.

show abstract

Inhibitory effect of PPARγ on NLRP3 inflammasome activation

Cited by 62 publications

References 73 publications

Leptin Signaling in the Ovary of Diet-Induced Obese Mice Regulates Activation of NOD-Like Receptor Protein 3 Inflammasome

Leptin Signaling in the Ovary of Diet-Induced Obese Mice Regulates Activation of NOD-Like Receptor Protein 3 Inflammasome

Rosiglitazone Alleviates Mechanical Allodynia of Rats with Bone Cancer Pain through the Activation of PPAR-γ to Inhibit the NF-κB/NLRP3 Inflammatory Axis in Spinal Cord Neurons

Leptin Signalling in the Ovary of Diet-Induced Obese Mice Regulates Activation of Nod-Like Receptor Protein 3 Inflammasome

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