PMID- 36126465
OWN - NLM
STAT- MEDLINE
DCOM- 20221005
LR  - 20221101
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 630
DP  - 2022 Nov 19
TI  - Tangeretin protects mice from diet-induced metabolic inflammation via activating 
      adipose lactate accumulation and macrophage M2 polarization.
PG  - 16-23
LID - S0006-291X(22)01294-3 [pii]
LID - 10.1016/j.bbrc.2022.09.044 [doi]
AB  - Infiltration by adipose tissue macrophages (ATMs) and subsequent metabolic 
      inflammation are the key causes of obesity-induced insulin resistance and 
      metabolic disorders. In this study, we analyzed the potential protective effect 
      of tangeretin, a key flavonoid found extensively in citrus peels, against 
      diet-induced metabolic inflammation. Daily gavages of tangeretin at 20 mg/kg 
      protected the mice from high fat diet (HFD) feeding-induced insulin resistance, 
      ATMs activation, and M1 macrophage polarization. Interestingly, in vitro assays 
      using bone marrow-derived macrophages (BMDMs) showed that tangeretin had only a 
      minimal effect on macrophage polarization. Assays of central carbon metabolism 
      (CCM) in adipose tissue showed that tangeretin treatment rerouted the carbon 
      metabolism and caused lactate accumulation in the microenvironment. Co-culture 
      assays further suggested that tangeretin enhanced M2 polarization of BMDMs when 
      adipocytes were present, whereas blocking the lactate uptake in macrophages 
      reversed the effect of tangeretin on polarization. Taken together, these findings 
      indicated that tangeretin provided indirect protection from diet-induced ATMs 
      activation by reprogramming glucose metabolism and promoting lactate accumulation 
      that subsequently promoted macrophage M2 polarization and reduced inflammation.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Sun, Yulin
AU  - Sun Y
AD  - Key Laboratory of the Model Animal Research, Animal Core Facility of Nanjing 
      Medical University, Nanjing, 211166, China.
FAU - Liu, Lu
AU  - Liu L
AD  - Department of Nutrition, the First Medical Center, Chinese PLA General Hospital, 
      Beijing, 100853, China.
FAU - Qiu, Chen
AU  - Qiu C
AD  - Key Laboratory of the Model Animal Research, Animal Core Facility of Nanjing 
      Medical University, Nanjing, 211166, China. Electronic address: 
      chenqiu@njmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220914
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Flavones)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 7440-44-0 (Carbon)
RN  - I4TLA1DLX6 (tangeretin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adipose Tissue/metabolism
MH  - Animals
MH  - Carbon/metabolism
MH  - Diet, High-Fat/adverse effects
MH  - *Flavones/pharmacology
MH  - Glucose/metabolism
MH  - Inflammation/metabolism
MH  - *Insulin Resistance
MH  - Lactic Acid/metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
OTO - NOTNLM
OT  - Adipocyte
OT  - Lactate
OT  - Macrophage
OT  - Metabolic inflammation
OT  - Tangeretin
COIS- Declaration of competing interest None
EDAT- 2022/09/21 06:00
MHDA- 2022/10/06 06:00
CRDT- 2022/09/20 18:21
PHST- 2022/09/09 00:00 [received]
PHST- 2022/09/10 00:00 [accepted]
PHST- 2022/09/21 06:00 [pubmed]
PHST- 2022/10/06 06:00 [medline]
PHST- 2022/09/20 18:21 [entrez]
AID - S0006-291X(22)01294-3 [pii]
AID - 10.1016/j.bbrc.2022.09.044 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2022 Nov 19;630:16-23. doi: 
      10.1016/j.bbrc.2022.09.044. Epub 2022 Sep 14.