Department of Human Health and Nutritional Sciences, University of Guelph, 50 Stone Rd E, Guelph, ON N1G 2W1, Canada.
Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC 3010, Australia.
Function (Oxf). 2022 Jul 19;3(5):zqac037. doi: 10.1093/function/zqac037. eCollection 2022.
Within brown adipose tissue (BAT), the brain isoform of creatine kinase (CKB) has been proposed to regulate the regeneration of ADP and phosphocreatine in a futile creatine cycle (FCC) that stimulates energy expenditure. However, the presence of FCC, and the specific creatine kinase isoforms regulating this theoretical model within white adipose tissue (WAT), remains to be fully elucidated. In the present study, creatine did not stimulate respiration in cultured adipocytes, isolated mitochondria or mouse permeabilized WAT. Additionally, while creatine kinase ubiquitous-type, mitochondrial (CKMT1) mRNA and protein were detected in human WAT, shRNA-mediated reductions in did not decrease submaximal respiration in cultured adipocytes, and ablation of CKMT1 in mice did not alter energy expenditure, mitochondrial responses to pharmacological β-adrenergic activation (CL 316, 243) or exacerbate the detrimental metabolic effects of consuming a high-fat diet. Taken together, these findings solidify CKMT1 as dispensable in the regulation of energy expenditure, and unlike in BAT, they do not support the presence of FCC within WAT.
在棕色脂肪组织 (BAT) 中，脑型肌酸激酶 (CKB) 被认为可以调节无效肌酸循环 (FCC) 中 ADP 和磷酸肌酸的再生，从而刺激能量消耗。然而，FCC 的存在以及在白色脂肪组织 (WAT) 中调节这一理论模型的特定肌酸激酶同工酶仍有待充分阐明。在本研究中，肌酸并未刺激培养的脂肪细胞、分离的线粒体或小鼠通透的 WAT 呼吸。此外，虽然在人 WAT 中检测到肌酸激酶普遍型、线粒体 (CKMT1) mRNA 和蛋白，但通过 shRNA 介导降低 CKMT1 水平不会降低培养的脂肪细胞中的亚最大呼吸作用，并且在小鼠中敲除 CKMT1 不会改变能量消耗、对药理学β-肾上腺素能激活（CL 316、243）的线粒体反应或加剧高脂肪饮食的有害代谢影响。综上所述，这些发现证实 CKMT1 在调节能量消耗方面是可有可无的，与 BAT 不同，它们不支持 WAT 中存在 FCC。
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