Adipocyte lysoplasmalogenase TMEM86A regulates plasmalogen homeostasis and protein kinase A-dependent energy metabolism.
Adipocyte lysoplasmalogenase TMEM86A regulates plasmalogen homeostasis and protein kinase A-dependent energy metabolism.
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DOI：
10.1038/s41467-022-31805-3
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发表时间：
2022-07-14
影响因子：
16.6
通讯作者：
Lee, Yun-Hee
中科院分区：
文献类型：
--
作者：
Cho, Yoon Keun;Yoon, Young Cheol;Im, Hyeonyeong;Son, Yeonho;Kim, Minsu;Saha, Abhirup;Choi, Cheoljun;Lee, Jaewon;Lee, Sumin;Kim, Jae Hyun;Kang, Yun Pyo;Jung, Young-Suk;Ha, Hong Koo;Seong, Je Kyung;Granneman, James G.;Kwon, Sung Won;Lee, Yun-Hee
脂肪组织浆磷脂原代谢失调与肥胖相关代谢疾病有关。我们报道，给小鼠喂食高脂肪饮食可降低脂肪组织溶酶原水平，并增加跨膜蛋白86a (TMEM86A)，一种推定的溶酶原酶。非靶向脂质组学分析表明，脂肪细胞特异性tmem86a敲除（AKO）可增加脂肪组织中溶胞浆malogen的含量，包括溶血磷脂酰乙醇胺18:0 （LPE P-18:0）。令人惊讶的是，TMEM86A AKO通过抑制磷酸二酯酶3B和升高环磷酸腺苷来增加蛋白激酶A信号通路。TMEM86A AKO上调线粒体氧化代谢，提高能量消耗，保护小鼠免受高脂肪喂养引起的代谢功能障碍。重要的是，通过补充LPE P-18:0， TMEM86A AKO的作用在体外和体内得到了很大程度的再现。人类肥胖患者脂肪组织中LPE P-18:0水平显著降低，提示抑制TMEM86A或补充溶酶plasmalogen可能是预防或治疗肥胖相关代谢性疾病的治疗方法。脂肪组织中plasmalogen代谢失调与代谢性疾病有关。在这里，作者描述了脂肪细胞TMEM86A作为溶酶原酶的作用，并表明其缺失对高脂肪饮食诱导的代谢疾病具有保护作用，这种作用可以通过补充18:0的溶磷脂酰乙醇胺来概括。
Dysregulation of adipose tissue plasmalogen metabolism is associated with obesity-related metabolic diseases. We report that feeding mice a high-fat diet reduces adipose tissue lysoplasmalogen levels and increases transmembrane protein 86 A (TMEM86A), a putative lysoplasmalogenase. Untargeted lipidomic analysis demonstrates that adipocyte-specific TMEM86A-knockout (AKO) increases lysoplasmalogen content in adipose tissue, including plasmenyl lysophosphatidylethanolamine 18:0 (LPE P-18:0). Surprisingly, TMEM86A AKO increases protein kinase A signalling pathways owing to inhibition of phosphodiesterase 3B and elevation of cyclic adenosine monophosphate. TMEM86A AKO upregulates mitochondrial oxidative metabolism, elevates energy expenditure, and protects mice from metabolic dysfunction induced by high-fat feeding. Importantly, the effects of TMEM86A AKO are largely reproduced in vitro and in vivo by LPE P-18:0 supplementation. LPE P-18:0 levels are significantly lower in adipose tissue of human patients with obesity, suggesting that TMEM86A inhibition or lysoplasmalogen supplementation might be therapeutic approaches for preventing or treating obesity-related metabolic diseases. Dysregulation of plasmalogen metabolism in adipose tissue is associated with metabolic diseases. Here the authors characterize the role of adipocyte TMEM86A as a lysoplasmalogenase and show its deletion is protective against high fat diet induced metabolic disease, an effect that can be recapitulated by plasmenyl lysophosphatidylethanolamine 18:0 supplementation.
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影响因子：
1.9
作者：
Mawatari S;Hazeyama S;Fujino T
通讯作者：
Fujino T
影响因子：
14.9
作者：
Haug K;Salek RM;Conesa P;Hastings J;de Matos P;Rijnbeek M;Mahendraker T;Williams M;Neumann S;Rocca-Serra P;Maguire E;González-Beltrán A;Sansone SA;Griffin JL;Steinbeck C
通讯作者：
Steinbeck C
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
5.9
作者：
Kim SN;Kwon HJ;Akindehin S;Jeong HW;Lee YH
通讯作者：
Lee YH
影响因子：
3.7
作者：
Kulyté A;Ehrlund A;Arner P;Dahlman I
通讯作者：
Dahlman I