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Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue.


ABSTRACT: 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.

SUBMITTER: Goldberg EL 

PROVIDER: S-EPMC10150608 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue.

Goldberg Emily L EL   Shchukina Irina I   Asher Jennifer L JL   Sidorov Sviatoslav S   Artyomov Maxim N MN   Dixit Vishwa Deep VD  

Nature metabolism 20200120 1


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 energ  ...[more]

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