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.