Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue

Emily L. Goldberg, Irina Shchukina, Jennifer L. Asher, Sviatoslav Sidorov, Maxim N. Artyomov, Vishwa Deep Dixit

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Pages (from-to)50-61
Number of pages12
JournalNature Metabolism
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2020

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