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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 Le  ;  Jin Won Cho  ;  Justin Y Jeon  ;  Yong-Ho Lee 
 FRONTIERS IN IMMUNOLOGY, Vol.13 : 843520, 2022-04 
Journal Title
Issue Date
3-Hydroxybutyric Acid / pharmacology ; Adult ; Diet, Ketogenic* ; Female ; Fibroblast Growth Factors ; Humans ; Inflammasomes* / metabolism ; Male ; NLR Family, Pyrin Domain-Containing 3 Protein / metabolism ; Young Adult
FGF21 ; IL-1β (interleukin 1β) ; Ketogenic diet (KD) ; NLRP3 inflammasome ; isocaloric ; β-hydroxybutyrate
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: clinicaltrials.gov (NCT02964572).
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Kim, So Ra(김소라)
Kim, Jeong Ho(김정호) ORCID logo https://orcid.org/0000-0003-2479-0548
Yu, Je Wook(유제욱) ORCID logo https://orcid.org/0000-0001-5943-4071
Lee, Myung Shik(이명식) ORCID logo https://orcid.org/0000-0003-3292-1720
Lee, Byung Wan(이병완) ORCID logo https://orcid.org/0000-0002-9899-4992
Lee, Sang-Guk(이상국) ORCID logo https://orcid.org/0000-0003-3862-3660
Lee, Yong Ho(이용호) ORCID logo https://orcid.org/0000-0002-6219-4942
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
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