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Loss of cAMP signaling in CD11c immune cells protects against diet-induced obesity
Diabetes ( IF 6.2 ) Pub Date : 2023-05-31 , DOI: 10.2337/db22-1035
Liping Zeng 1, 2 , D Scott Herdman 2 , Sung Min Lee 2 , Ailin Tao 1 , Manasi Das 2 , Samuel Bertin 2 , Lars Eckmann 2 , Sushil K Mahata 2, 3 , Panyisha Wu 2 , Miki Hara 4 , Ji-Won Byun 5 , Shwetha Devulapalli 6 , Hemal H Patel 3, 6 , Anthony J A Molina 2 , Olivia Osborn 2 , Maripat Corr 2 , Eyal Raz 2 , Nicholas J G Webster 2, 3, 7
Affiliation  

In obesity, CD11c+ innate immune cells are recruited to adipose tissue and create an inflammatory state that causes both insulin and catecholamine resistance. We found that ablation of Gnas, the gene that encodes Gαs, in CD11c expressing cells protects mice from obesity, glucose intolerance, and insulin resistance. Transplantation studies showed that the lean phenotype was conferred by bone marrow-derived cells and did not require adaptive immunity. Loss of cAMP signaling was associated with increased adipose tissue norepinephrine and cAMP signaling, and prevention of catecholamine resistance. The adipose tissue had reduced expression of catecholamine transport and degradation enzymes suggesting that the elevated norepinephrine resulted from decreased catabolism. Collectively, our results identified an important role for cAMP signaling in CD11c+ innate immune cells in whole-body metabolism by controlling norepinephrine levels in WAT, modulating catecholamine-induced lipolysis, and increasing thermogenesis, which together created a lean phenotype.

中文翻译:


CD11c 免疫细胞中 cAMP 信号丢失可预防饮食引起的肥胖



在肥胖症中,CD11c+先天免疫细胞被招募到脂肪组织并产生炎症状态,导致胰岛素和儿茶酚胺抵抗。我们发现,CD11c 表达细胞中 Gnas(编码 Gαs 的基因)的消除可以保护小鼠免受肥胖、葡萄糖不耐受和胰岛素抵抗的影响。移植研究表明,瘦表型是由骨髓来源的细胞赋予的,不需要适应性免疫。 cAMP 信号传导的丧失与脂肪组织去甲肾上腺素和 cAMP 信号传导的增加以及儿茶酚胺抵抗的预防相关。脂肪组织中儿茶酚胺转运和降解酶的表达减少,表明去甲肾上腺素升高是由于分解代谢减少所致。总的来说,我们的结果确定了 CD11c+ 先天免疫细胞中的 cAMP 信号传导在全身代谢中的重要作用,通过控制 WAT 中的去甲肾上腺素水平、调节儿茶酚胺诱导的脂肪分解和增加生热作用,这些共同创造了瘦表型。
更新日期:2023-05-31
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