Adipocyte P2Y14 receptors play a key role in regulating whole-body glucose and lipid homeostasis

Jain, Shanu; Pydi, Sai Prasad; Jung, Young‐Hwan; Scortichini, Mirko; Kesner, Efrat; Karcz, Tadeusz; Cook, Donald N.; Гаврилова, Оксана; Wess, Jürgen

doi:10.1172/jci.insight.146577

Cited by 19 publications

(11 citation statements)

References 48 publications

(81 reference statements)

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“…Platelets control liver tumor growth through P2Y 12 R-dependent CD40L release in NAFLD [ 41 ]. Another study revealed that mice lacking P2Y 14 R selectively in adipocytes were protected from obesity and displayed reduced liver weight compared to HFD control mice [ 42 ]. Reduced obesity and hepatic steatosis further contributed to improved insulin sensitivity in the liver of adipocyte-P2Y 14 R KO mice [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Another study revealed that mice lacking P2Y 14 R selectively in adipocytes were protected from obesity and displayed reduced liver weight compared to HFD control mice [ 42 ]. Reduced obesity and hepatic steatosis further contributed to improved insulin sensitivity in the liver of adipocyte-P2Y 14 R KO mice [ 42 ]. On the other hand, P2Y 6 R is known to couple with G 12/13 .…”

Section: Discussionmentioning

confidence: 99%

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Knockout of Purinergic P2Y6 Receptor Fails to Improve Liver Injury and Inflammation in Non-Alcoholic Steatohepatitis

Nishiyama

Ariyoshi

Nishimura

et al. 2023

IJMS

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Nonalcoholic steatohepatitis (NASH) is a disease that progresses from nonalcoholic fatty liver (NAFL) and which is characterized by inflammation and fibrosis. The purinergic P2Y6 receptor (P2Y6R) is a pro-inflammatory Gq/G12 family protein-coupled receptor and reportedly contributes to intestinal inflammation and cardiovascular fibrosis, but its role in liver pathogenesis is unknown. Human genomics data analysis revealed that the liver P2Y6R mRNA expression level is increased during the progression from NAFL to NASH, which positively correlates with inductions of C-C motif chemokine 2 (CCL2) and collagen type I α1 chain (Col1a1) mRNAs. Therefore, we examined the impact of P2Y6R functional deficiency in mice crossed with a NASH model using a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Feeding CDAHFD for 6 weeks markedly increased P2Y6R expression level in mouse liver, which was positively correlated with CCL2 mRNA induction. Unexpectedly, the CDAHFD treatment for 6 weeks increased liver weights with severe steatosis in both wild-type (WT) and P2Y6R knockout (KO) mice, while the disease marker levels such as serum AST and liver CCL2 mRNA in CDAHFD-treated P2Y6R KO mice were rather aggravated compared with those of CDAHFD-treated WT mice. Thus, P2Y6R may not contribute to the progression of liver injury, despite increased expression in NASH liver.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Knockout of Purinergic P2Y6 Receptor Fails to Improve Liver Injury and Inflammation in Non-Alcoholic Steatohepatitis

Nishiyama

Ariyoshi

Nishimura

et al. 2023

IJMS

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“…In addition to HO-1, bioactive flavanones also regulate the ferroptosis process through the GPX4-GSH system. P2Y 14 is a G-protein coupled receptor expressed in multiple cells, which is closely related to the occurrence and development of diabetes. , Naringin, a natural glycoside of naringenin, could regulate the NRF2/GPX4 pathway by inhibiting the P2Y 14 receptor in satellite glial cells in the superior cervical ganglia, thereby improving diabetic cardiac autonomic neuropathy (DCAN) . It has been reported that collagenase-induced tendinopathy rats exhibit iron accumulation, increased MDA levels, as well as decreased GPX4, SLC7A11, and FSP1 levels in Achilles tendons, indicating that ferroptosis participate in the pathological process of tendinopathy .…”

Section: Natural Flavonoids Targeting Ferroptosismentioning

confidence: 99%

Natural Flavonoids and Ferroptosis: Potential Therapeutic Opportunities for Human Diseases

Zhou

Zhang

2023

J. Agric. Food Chem.

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Flavonoids are a class of bioactive phytochemicals containing a core 2-phenylchromone skeleton and are widely found in fruits, vegetables, and herbs. Such natural compounds have gained significant attention due to their various health benefits. Ferroptosis is a recently discovered unique iron-dependent mode of cell death. Unlike traditional regulated cell death (RCD), ferroptosis is associated with excessive lipid peroxidation on cellular membranes. Accumulating evidence suggests that this form of RCD is involved in a variety of physiological and pathological processes. Notably, multiple flavonoids have been shown to be effective in preventing and treating diverse human diseases by regulating ferroptosis. In this review, we introduce the key molecular mechanisms of ferroptosis, including iron metabolism, lipid metabolism, and several major antioxidant systems. Additionally, we summarize the promising flavonoids targeting ferroptosis, which provides novel ideas for the management of diseases such as cancer, acute liver injury, neurodegenerative diseases, and ischemia/reperfusion (I/R) injury.

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“…However, no data on COVID-19 or mucormycosis patients are available to date. P2Y14 expression is linked to glucose and lipid homeostasis [136], as well as the amplification of allergen-induced hyperinflammatory airway eosinophilia [135]. The HBP pathway has also been recently linked to ferroptosis sensitivity [137], thereby indicating a potential druggable "diabetes-HBP-mucin-iron axis" in COVID-19 and mucormycosis infections.…”

Section: Hexosamine Biosynthetic Pathway Of Glycosylation and Metabol...mentioning

confidence: 99%

Diabetology: Feature Papers 2021

2022

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Adipocyte P2Y14 receptors play a key role in regulating whole-body glucose and lipid homeostasis

Cited by 19 publications

References 48 publications

Knockout of Purinergic P2Y6 Receptor Fails to Improve Liver Injury and Inflammation in Non-Alcoholic Steatohepatitis

Knockout of Purinergic P2Y6 Receptor Fails to Improve Liver Injury and Inflammation in Non-Alcoholic Steatohepatitis

Natural Flavonoids and Ferroptosis: Potential Therapeutic Opportunities for Human Diseases

Diabetology: Feature Papers 2021

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