التفاصيل البيبلوغرافية
العنوان: |
O-linked N-acetylglucosamine modification is essential for physiological adipose expansion induced by high-fat feeding. |
المؤلفون: |
Akiko Nakamoto, Natsuko Ohashi, Lucia Sugawara, Katsutaro Morino, Shogo Ida, Perry, Rachel J., Ikki Sakuma, Tsuyoshi Yanagimachi, Yukihiro Fujita, Satoshi Ugi, Shinji Kume, Shulman, Gerald I., Hiroshi Maegawa |
المصدر: |
American Journal of Physiology: Endocrinology & Metabolism; Jul2023, Vol. 325 Issue 1, pE46-E61, 16p |
مصطلحات موضوعية: |
N-acetylglucosamine, ADIPOSE tissues, WEIGHT gain, FREE fatty acids, REGULATION of body weight, MACROPHAGE inflammatory proteins, INSULIN |
مستخلص: |
Adipose tissues accumulate excess energy as fat and heavily influence metabolic homeostasis. O-linked N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), which involves the addition of N-acetylglucosamine to proteins by O-GlcNAc transferase (Ogt), modulates multiple cellular processes. However, little is known about the role of O-GlcNAcylation in adipose tissues during body weight gain due to overnutrition. Here, we report on O-GlcNAcylation in mice with high-fat diet (HFD)-induced obesity. Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less body weight than control mice under HFD. Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced body weight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. Primary cultured adipocytes derived from Ogt-FKO mice showed decreased lipid accumulation. Both primary cultured adipocytes and 3T3-L1 adipocytes treated with OGT inhibitor showed increased secretion of free fatty acids. Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. In conclusion, O-GlcNAcylation is important for healthy adipose expansion in mice. Glucose flux into adipose tissues may be a signal to store excess energy as fat. [ABSTRACT FROM AUTHOR] |
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قاعدة البيانات: |
Complementary Index |