Methylglyoxal attenuates isoproterenol-induced increase in uncoupling protein 1 expression through activation of JNK signaling pathway in beige adipocytes

Ng, Su-Ping; Nomura, Wataru; Takahashi, Haruya; Inoue, Kazuo; Kawada, Teruo; Goto, Tsuyoshi

doi:10.1016/j.bbrep.2021.101127

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…Previous studies have reported that isoproterenol concentrations of 1-10 µM increase the expression of UCP1 and PGC-1α, thereby inducing the browning of white adipocytes in primary cultures derived from human and mouse white adipose tissue [36,45,46]. Furthermore, the browning of white adipocytes into beige adipocytes has been associated with enhanced lipid metabolism and reduced lipid droplet size [47,48].…”

Section: Discussionmentioning

confidence: 99%

Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway

Kim,

Yazawa,

Koide

et al. 2024

Biology

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Adipose tissue plays an important role in regulating body temperature and metabolism, with white adipocytes serving as storage units for energy. Recent research focused on the browning of white adipocytes (beige adipocytes), causing thermogenesis and lipolysis. The process of browning is linked to the activation of uncoupling protein (UCP) expression, which can be mediated by the β3 adrenergic receptor pathway. Transcriptional factors, such as peroxisome proliferator activated receptor γ (PPARγ) and PPARγ coactivator 1 alpha, play vital roles in cell fate determination for fat cells. Beige adipocytes have metabolic therapeutic potential to combat diseases such as obesity, diabetes mellitus, and dyslipidemia, owing to their significant impact on metabolic functions. However, the molecular mechanisms that cause the induction of browning are unclear. Therefore, research using animal models and primary culture is essential to provide an understanding of browning for further application in human metabolic studies. Pigs have physiological similarities to humans; hence, they are valuable models for research on adipose tissue. This study demonstrates the browning potential of pig white adipocytes through primary culture experiments. The results show that upregulation of UCP3 gene expression and fragmentation of lipid droplets into smaller particles occur due to isoproterenol stimulation, which activates beta-adrenergic receptor signaling. Furthermore, PPARγ and PGC-1α were found to activate the UCP3 promoter region, similar to that of UCP1. These findings suggest that pigs undergo metabolic changes that induce browning in white adipocytes, providing a promising approach for metabolic research with potential implications for human health. This study offers valuable insights into the mechanism of adipocyte browning using pig primary culture that can enhance our understanding of human metabolism, leading to cures for commonly occurring diseases.

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Section: Discussionmentioning

confidence: 99%

Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway

Kim,

Yazawa,

Koide

et al. 2024

Biology

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Methylglyoxal induces multiple serine phosphorylation in insulin receptor substrate 1 via the TAK1–p38–mTORC1 signaling axis in adipocytes

Nomura

Takahashi

et al. 2022

Biochemical Journal

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Certain metabolic intermediates produced during metabolism are known to regulate a wide range of cellular processes. Methylglyoxal (MG), a natural metabolite derived from glycolysis, has been shown to negatively influences systemic metabolism by inducing glucose intolerance, insulin resistance, and diabetic complications. MG plays a functional role as a signaling molecule that initiates signal transduction. However, the specific relationship between MG-induced activation of signal transduction and its negative effects on metabolism remains unclear. Here, we found that MG activated mammalian target of rapamycin complex 1 (mTORC1) signaling via p38 mitogen-activated protein kinase in adipocytes, and that the transforming growth factor-b-activated kinase 1 (TAK1) is needed to activate p38–mTORC1 signaling following treatment with MG. We also found that MG increased the phosphorylation levels of serine residues in insulin receptor substrate (IRS)-1, which is involved in its negative regulation, thereby attenuating insulin-stimulated tyrosine phosphorylation in IRS-1. The negative effect of MG on insulin-stimulated IRS-1 tyrosine phosphorylation was exerted due to the MG-induced activation of the TAK1–p38–mTORC1 signaling axis. The involvement of the TAK1–p38–mTORC1 signaling axis in the induction of IRS-1 multiple serine phosphorylation was not unique to MG, as the proinflammatory cytokine, tumor necrosis factor-α, also activated the same signaling axis. Therefore, our findings suggest that MG-induced activation of the TAK1–p38–mTORC1 signaling axis caused multiple serine phosphorylation on IRS-1, potentially contributing to insulin resistance.

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Dietary glycation compounds – implications for human health

Hellwig,

Diel,

Eisenbrand

et al. 2024

Critical Reviews in Toxicology

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Methylglyoxal attenuates isoproterenol-induced increase in uncoupling protein 1 expression through activation of JNK signaling pathway in beige adipocytes

Cited by 3 publications

References 48 publications

Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway

Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway

Methylglyoxal induces multiple serine phosphorylation in insulin receptor substrate 1 via the TAK1–p38–mTORC1 signaling axis in adipocytes

Dietary glycation compounds – implications for human health

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