Short Term Isocaloric Ketogenic Diet Modulates NLRP3 Inflammasome Via B-hydroxybutyrate and Fibroblast Growth Factor 21

Eun Ran Kim, So Ra Kim, Wonhee Cho, Sang Guk Lee, Soo Hyun Kim, Jin Hee Kim, Eunhye Choi, Jeong Ho Kim, Je Wook Yu, Byung Wan Lee, Eun Seok Kang, Bong Soo Cha, Myung Shik Lee, Jin Won Cho, Justin Y. Jeon, Yong Ho Lee

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5 Citations (Scopus)


A ketogenic diet (KD) is known to have beneficial health effects. Various types of KD interventions have been applied to manage metabolic syndrome based on modification of diet parameters such as duration of intervention, macronutrient components, and total calories. Nevertheless, the beneficial health impact of isocaloric KD is largely unknown, especially in healthy subjects. The present study investigated the acute effects of a 3-day isocaloric KD. In this non-randomized intervention study, we recruited 15 healthy volunteers aged 24-38 years (7 men and 8 women) and placed them on an isocaloric KD restricting intake of carbohydrates but not energy (75% fat, 20% protein, 5% carbohydrate) for 3 days. Biochemical profiles and laboratory measurements were performed. Peripheral blood monocular cells were cultured, and measured cell stimulated cytokines. After short-term isocaloric KD, subjects lost body weight and serum free fatty acid levels were increased. These results accompanied elevated serum β-hydroxybutyrate (BHB) concentration and fibroblast growth factor 21 (FGF21) levels and improved insulin sensitivity. Regarding the direct effect of BHB on inflammasome activation, interleukin-1β (IL-1β) and tumor necrosis factor-α secretion in response to adenosine triphosphate or palmitate stimulation in human macrophages decreased significantly after isocaloric KD. In ex-vivo experiments with macrophages, both FGF21 and BHB further reduced IL-1β secretion compared to either BHB or FGF21 alone. The inhibitory effect of FGF21 on IL-1β secretion was blunted with bafilomycin treatment, which blocked autophagy flux. In conclusion, isocaloric KD for 3 days is a promising approach to improve metabolic and inflammatory status. Clinical Trial Registration: (NCT02964572).

Original languageEnglish
Article number843520
JournalFrontiers in Immunology
Publication statusPublished - 2022 Apr 28

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP) [NRF-2016R1A5A1010764] and [NRF-2019R1l1A1A01063695] and was also supported by a faculty research grant of Yonsei University College of Medicine for (6-2015-0069). The study funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report.

Publisher Copyright:
Copyright © 2022 Kim, Kim, Cho, Lee, Kim, Kim, Choi, Kim, Yu, Lee, Kang, Cha, Lee, Cho, Jeon and Lee.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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