Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue.
Emily L GoldbergIrina ShchukinaJennifer L AsherSviatoslav SidorovMaxim N ArtyomovVishwa Deep DixitPublished in: Nature metabolism (2020)
Ketone bodies are essential alternative fuels that allow humans to survive periods of glucose scarcity induced by starvation and prolonged exercise. A widely used ketogenic diet (KD), which is extremely high in fat with very low carbohydrates, drives the host into using β-hydroxybutyrate for the production of ATP and lowers NLRP3-mediated inflammation. However, the extremely high fat composition of KD raises the question of how ketogenesis affects adipose tissue to control inflammation and energy homeostasis. Here, by using single-cell RNA sequencing of adipose-tissue-resident immune cells, we show that KD expands metabolically protective γδ T cells that restrain inflammation. Notably, long-term ad libitum KD feeding in mice causes obesity, impairs metabolic health and depletes the adipose-resident γδ T cells. In addition, mice lacking γδ T cells have impaired glucose homeostasis. Our results suggest that γδ T cells are mediators of protective immunometabolic responses that link fatty acid-driven fuel use to reduced adipose tissue inflammation.
Keyphrases
- adipose tissue
- insulin resistance
- high fat diet induced
- oxidative stress
- high fat diet
- single cell
- fatty acid
- public health
- weight loss
- type diabetes
- patient safety
- metabolic syndrome
- high throughput
- blood pressure
- health information
- social media
- high intensity
- resistance training
- climate change
- body mass index
- glycemic control