Department of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT, USA.
Division of Endocrinology, Department of Internal Medicine, Carver College of Medicine, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa City, IA, 52242, USA.
Sci Rep. 2022 May 4;12(1):7273. doi: 10.1038/s41598-022-11219-3.
Ectopic ceramide accumulation in insulin-responsive tissues contributes to the development of obesity and impairs insulin sensitivity. Moreover, pharmacological inhibition of serine palmitoyl transferase (SPT), the first enzyme essential for ceramide biosynthesis using myriocin in rodents reduces body weight and improves insulin sensitivity and associated metabolic indices. Myriocin was originally extracted from fruiting bodies of the fungus Isaria sinclairii and has been found abundant in a number of closely related fungal species such as the Cordyceps. Myriocin is not approved for human use but extracts from Cordyceps are routinely consumed as part of traditional Chinese medication for the treatment of numerous diseases including diabetes. Herein, we screened commercially available extracts of Cordyceps currently being consumed by humans, to identify Cordyceps containing myriocin and test the efficacy of Cordyceps extract containing myriocin in obese mice to improve energy and glucose homeostasis. We demonstrate that commercially available Cordyceps contain variable amounts of myriocin and treatment of mice with a human equivalent dose of Cordyceps extract containing myriocin, reduces ceramide accrual, increases energy expenditure, prevents diet-induced obesity, improves glucose homeostasis and resolves hepatic steatosis. Mechanistically, these beneficial effects were due to increased adipose tissue browning/beiging, improved brown adipose tissue function and hepatic insulin sensitivity as well as alterations in the abundance of gut microbes such as Clostridium and Bilophila. Collectively, our data provide proof-of-principle that myriocin containing Cordyceps extract inhibit ceramide biosynthesis and attenuate metabolic impairments associated with obesity. Moreover, these studies identify commercially available Cordyceps as a readily available supplement to treat obesity and associated metabolic diseases.
在胰岛素反应组织中异位神经酰胺的积累导致肥胖的发展，并损害胰岛素敏感性。此外，使用米酵菌酸抑制丝氨酸棕榈酰转移酶（SPT），这是神经酰胺生物合成的第一个必需酶，在啮齿动物中可降低体重并改善胰岛素敏感性和相关代谢指标。米酵菌酸最初是从真菌虫草属的子实体中提取的，并且在许多密切相关的真菌物种中发现了丰富的虫草属，如虫草属。米酵菌酸尚未被批准用于人类使用，但虫草属的提取物通常作为传统中药的一部分用于治疗多种疾病，包括糖尿病。在此，我们筛选了目前人类正在食用的市售虫草属提取物，以鉴定含有米酵菌酸的虫草属，并测试含有米酵菌酸的虫草属提取物对肥胖小鼠的功效，以改善能量和葡萄糖稳态。我们证明市售虫草属含有不同量的米酵菌酸，用含有米酵菌酸的虫草属提取物治疗相当于人类的等效剂量，可减少神经酰胺的积累，增加能量消耗，防止饮食诱导的肥胖，改善葡萄糖稳态并解决肝脂肪变性。从机制上讲，这些有益的影响是由于脂肪组织褐变/米色增加、改善棕色脂肪组织功能和肝胰岛素敏感性以及肠道微生物如拟杆菌属和比氏双歧杆菌属的丰度改变所致。总的来说，我们的数据提供了原理上的证据，表明含有米酵菌酸的虫草属提取物可抑制神经酰胺的生物合成，并减轻与肥胖相关的代谢损伤。此外，这些研究确定了市售虫草属作为一种现成的补充剂，可用于治疗肥胖和相关代谢疾病。
