Abstract
BackgroundIntermittent or prolonged exposure to severe cold stress disturbs energy homeostasis and can lead to hypothermia, heart failure, Alzheimer’s disease, and so on. As the typical “hot” traditional Chinese medicine, Aconite has been widely used to treat cold-associated diseases for thousands of years, but its critical mechanisms for the promotion of thermogenesis are not fully resolved. Gut microbiota and its metabolites play a crucial role in maintaining energy homeostasis. Here, we investigated whether the aqueous extracts of Aconite (AA) can enhance thermogenesis through modulation of the composition and metabolism of gut microbiota in hypothermic rats.MethodsThe therapeutic effects of AA on body temperature, energy intake, and the histopathology of white adipose tissue and brown adipose tissue of hypothermic rats were assessed. Microbiota analysis based on 16 S rRNA and targeted metabolomics for bile acids (BAs) were used to evaluate the composition of gut microbiota and BAs pool. The antibiotic cocktail treatment was adopted to further confirm the relationship between the gut microbiota and the thermogenesis-promoting effects of AA.ResultsOur results showed a sharp drop in rectal temperature and body surface temperature in hypothermic rats. Administration of AA can significantly increase core body temperature, surface body temperature, energy intake, browning of white adipose tissue, and thermogenesis of brown adipose tissue. Importantly, these ameliorative effects of AA were accompanied by the shift of the disturbed composition of gut microbiota toward a healthier profile and the increased levels of BAs. In addition, the depletion of gut microbiota and the reduction of BAs caused by antibiotic cocktails reduced the thermogenesis-promoting effect of AA.ConclusionsOur results demonstrated that AA promoted thermogenesis in rats with hypothermia via regulating gut microbiota and BAs metabolism. Our findings can also provide a novel solution for the treatment of thermogenesis-associated diseases such as rheumatoid arthritis, obesity, and type 2 diabetes.
Highlights
Intermittent or prolonged exposure to severe cold stress disturbs energy homeostasis and can lead to hypothermia, heart failure, Alzheimer’s disease, and so on
aqueous extracts of Aconite (AA) improves hypothermia and increases energy intake To investigate the effects of severe cold exposure, we monitored the body temperature including rectal temperature and eye temperature, as well as ventral and dorsal temperature
Recent studies have shown that polysaccharides and other types of drugs with low bioavailability can act on gut microbiota to achieve therapeutic effects, we investigated the effects of AA on gut microbiota
Summary
Intermittent or prolonged exposure to severe cold stress disturbs energy homeostasis and can lead to hypothermia, heart failure, Alzheimer’s disease, and so on. Intermittent or prolonged exposure to severe cold stress, a condition that the heat produced cannot compensate for the heat released into the environment, disturbs the homeostasis, resulting in pathological insufficiency of energy metabolism that can be manifested as hypothermia [3]. The major approach to maintaining body temperature in a cold environment depends on protective measures, such as adding clothing or other items [9, 10] These physical methods only help reduce heat dissipation and cannot restore the homeostasis of energy metabolism
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