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Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice

July 18, 2024
in Health
Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice
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Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice

The mechanism of action of pyruvate by targeting cPLA2 and inhibiting cPLA2-mediated downstream signaling. Credit: Sadaf Hasan, Nabil Ghani, Xiangli Zhao, Julia Good, Amanda Huang, Hailey Lynn Wrona, Jody Liu, Chuan-ju Liu

An article in Protein & Cell discusses the multifactorial nature of obesity, highlighting its association with chronic low-grade inflammation, or meta-inflammation, which contributes to metabolic disorders. The paper is titled “Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice.”

Pyruvate, a glycolytic metabolite, was found to inhibit adipogenic differentiation in vitro and significantly prevent HFD-induced weight gain and inflammation in mice. Through drug affinity responsive target stability, proteomics, and cellular thermal shift assays, cPLA2 was identified as a target of pyruvate.

Mice with global cPLA2 ablation showed diminished protective effects of pyruvate, confirming the importance of the pyruvate/cPLA2 interaction in mitigating obesity and inflammation. The study underscores pyruvate’s potential as a therapeutic option for obesity, given its previous clinical use and safety.

Key findings from the study include:

Pyruvate was shown to inhibit the differentiation of preadipocytes into adipocytes. In vitro studies demonstrated that pyruvate downregulated key adipogenic transcriptional markers such as PPARγ and CEBPα, along with adipocyte-related genes like Fabp4. Pyruvate reduced intracellular lipid and triglyceride accumulation, indicating its effectiveness in suppressing adipogenesis across different cell types.
In vivo experiments with male C57BL/6 mice indicated that pyruvate administration significantly prevented HFD-induced weight gain and central adiposity. Pyruvate-treated mice exhibited lower body weights and reduced abdominal circumferences compared to untreated HFD-fed mice. This was accompanied by a decrease in white adipose tissue (WAT) inflammation and metabolic dysregulation.
The study identified cPLA2 as a novel target of pyruvate using drug affinity responsive target stability, proteomics, and cellular thermal shift assays. cPLA2 plays a critical role in adipocytic differentiation and chronic inflammation. Mice with global ablation of cPLA2 displayed a significant reduction in the protective effects of pyruvate, confirming the interaction between pyruvate and cPLA2 as essential for mitigating inflammation and obesity.
Reduction of Inflammatory Markers: Pyruvate administration resulted in the downregulation of various inflammatory genes, including IL-6, IL-1B, CCL2, and TNFα. The study showed that pyruvate’s anti-inflammatory effects were mediated through the inhibition of cPLA2, which in turn reduced the NF-κB-dependent expression of pro-inflammatory cytokines.

The study establishes pyruvate as a promising therapeutic agent against obesity and its related inflammatory and metabolic disorders. By targeting cPLA2, pyruvate effectively inhibits adipogenesis, reduces WAT inflammation, and prevents HFD-induced weight gain.

These findings highlight the potential of pyruvate as an anti-inflammatory and anti-obesity supplement that could be integrated into regular diets or used as a dietary supplement.

Given its previous clinical use, pyruvate presents a safe and viable alternative for obesity treatment. The study’s insights into the molecular mechanisms of pyruvate provide a basis for further research and development of pyruvate-based interventions for metabolic diseases.

More information:
Sadaf Hasan et al, Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice, Protein & Cell (2024). DOI: 10.1093/procel/pwae014

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Citation:
Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice (2024, July 17)
retrieved 18 July 2024
from https://medicalxpress.com/news/2024-07-dietary-pyruvate-cytosolic-phospholipase-a2.html

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part may be reproduced without the written permission. The content is provided for information purposes only.

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