PMID- 36920218
OWN - NLM
STAT- MEDLINE
DCOM- 20230419
LR  - 20230421
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 324
IP  - 5
DP  - 2023 May 1
TI  - Inhibition of glutaminase 1 activity reverses airway hyperresponsiveness and 
      decreases IL-1beta(+) M1s and IL-17 producing ILC3s in high-fat diet-fed obese mice.
PG  - L625-L638
LID - 10.1152/ajplung.00181.2022 [doi]
AB  - In obesity, disturbed glutamine metabolism contributes to enhanced inflammation 
      by inducing alterations in immune cells. As macrophages and innate lymphoid cells 
      (ILCs) are known to be involved in the pathogenesis of obesity-related asthma, we 
      tested our hypothesis that altered glutamine metabolism may link obesity to 
      airway hyperresponsivenss (AHR), a cardinal feature of asthma, focusing on these 
      innate immune cells. Four-week-old male C57BL/6 mice were fed a high-fat diet 
      (HFD) for 13 wk in the presence or absence of BPTES 
      [Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide, a selective 
      inhibitor of glutaminase 1 which converts glutamine to glutamate] and their 
      blood, lung, and adipose tissues were analyzed. We then conducted in vitro 
      experiments using bone marrow-derived macrophages (BMDMs) and mouse alveolar 
      macrophage cell line. Furthermore, we investigated plasma glutamine and glutamate 
      levels in obese and nonobese asthmatics. BPTES treatment prevented HFD-induced 
      AHR and significantly decreased IL-1beta(+) classically activated macrophages (M1s) 
      and type 3 ILCs (ILC3s) which increased in the lungs of HFD-fed obese mice. In in 
      vitro experiments, BPTES treatment or glutamine supplement significantly reduced 
      the proportion of IL-1beta(+)NLRP3(+) M1s in lipopolysaccharide-stimulated BMDMs and 
      mouse alveolar macrophage cell line. BPTES treatment also significantly reduced 
      the IL-17 producing ILC3s differentiated from ILCs in naive mouse lung. In 
      addition, plasma glutamate/glutamine ratios were significantly higher in obese 
      asthmatics compared to nonobese asthmatics. Inhibition of glutaminolysis reverses 
      AHR in HFD-induced obese mice and decreases IL-1beta( + )NLRP3(+) M1s and IL-17 
      producing ILC3s, which suggests altered glutamine metabolism may have a role in 
      the pathogenesis of obesity-related AHR.
FAU - Shim, Ji-Su
AU  - Shim JS
AD  - Department of Internal Medicine, Ewha Womans University College of Medicine, 
      Seoul, Korea.
FAU - Lee, Hyun-Seung
AU  - Lee HS
AD  - Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
FAU - Kwon, Hyuktae
AU  - Kwon H
AD  - Department of Family Medicine, Seoul National University Hospital, Seoul, Korea.
FAU - Kim, Min-Hye
AU  - Kim MH
AD  - Department of Internal Medicine, Ewha Womans University College of Medicine, 
      Seoul, Korea.
FAU - Cho, Young-Joo
AU  - Cho YJ
AD  - Department of Internal Medicine, Ewha Womans University College of Medicine, 
      Seoul, Korea.
FAU - Park, Heung-Woo
AU  - Park HW
AUID- ORCID: 0000-0002-6970-3228
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Korea.
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230315
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Glutamates)
RN  - EC 3.5.1.2 (Glutaminase)
RN  - 0RH81L854J (Glutamine)
RN  - 0 (Interleukin-17)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Il17a protein, mouse)
RN  - 0 (Interleukin-1beta)
SB  - IM
MH  - Animals
MH  - Male
MH  - Mice
MH  - *Asthma/metabolism
MH  - Diet, High-Fat/adverse effects
MH  - Glutamates
MH  - Glutaminase
MH  - Glutamine/pharmacology/metabolism
MH  - Immunity, Innate
MH  - Interleukin-17
MH  - Lymphocytes
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - Obesity/complications
MH  - *Respiratory Hypersensitivity/metabolism
MH  - Interleukin-1beta
OTO - NOTNLM
OT  - asthma
OT  - glutamine
OT  - innate lymphoid cells
OT  - macrophages
OT  - obesity
EDAT- 2023/03/16 06:00
MHDA- 2023/04/17 06:41
CRDT- 2023/03/15 10:06
PHST- 2023/04/17 06:41 [medline]
PHST- 2023/03/16 06:00 [pubmed]
PHST- 2023/03/15 10:06 [entrez]
AID - 10.1152/ajplung.00181.2022 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2023 May 1;324(5):L625-L638. doi: 
      10.1152/ajplung.00181.2022. Epub 2023 Mar 15.