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Targeting NLRP3 inflammasome as a chief instigator of obesity, contributing to local adipose tissue inflammation and insulin resistance

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Abstract

Inflammasome activity plays a vital role in various non-microbial disease states correlated with prolonged inflammation. NLRP3 inflammasome function and IL-1β formation are augmented in obesity and several obesity-linked metabolic disorders (i.e. diabetes mellitus, hypertension, hepatic steatosis, cancer, arthritis, and sleep apnea). Also, several factors are associated with the progression of diseases viz. increased plasma glucose, fatty acids, and β-amyloid are augmented during obesity and activate NLRP3 inflammasome expression. Prolonged NLRP3 stimulation seems to play significant role in various disorders, though better knowledge of inflammasome regulation and action might result in improved therapeutic tactics. Numerous compounds that mitigate NLRP3 inflammasome expression and suppress its chief effector, IL-1β are presently studied in clinical phases as therapeutics to manage or prevent these common disorders. A deep research on the literature available till date for inflammasome in obesity was conducted using various medical sites like PubMed, HINARI, MEDLINE from the internet, and data was collected simultaneously. The present review aims to examine the prospects of inflammasome as a major progenitor in the progression of obesity via directing their role in regulating appetite.

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Abbreviations

NLRP3:

NLR family pyrin domain containing 3

IL:

interleukin

NOD:

nucleotide-binding oligomerization domain

NLRs:

NOD-like receptors

ASC:

apoptosis-associated speck-like protein containing a caspase recruitment domain

DAMP:

damage-associated molecular patter

HFD:

high-fat diet

PRRs:

pattern-recognition receptors

PYD:

pyrin domain

STAT :

signal transducer and activator of transcription

ROS:

reactive oxygen species

TRAF:

TNF receptor-associated factor

P2RX7:

P2X purinoceptor

JNK:

c-Jun N terminal kinase

PRRs:

pathogen recognition receptors

BMI:

body mass index

NE:

norepinephrine

AABs:

aged adipose B cells

MSC:

mesenchymal stem cells

ECM:

extracellular matrix

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  1. Aayush Sehgal and Tapan Behl contributed equally to this work.

Authors and Affiliations

  1. Chitkara College of Pharmacy, Chitkara University, Punjab, India

    Aayush Sehgal, Tapan Behl, Ishnoor Kaur, Sukhbir Singh & Neelam Sharma

  2. Chrono-Environment Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, Besancon, France

    Lotfi Aleya

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  1. Aayush Sehgal
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AS and TB: Conceived the study and wrote the first draft of the paper; IK, SS and NS: Data compilation; LA: Proof read

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Sehgal, A., Behl, T., Kaur, I. et al. Targeting NLRP3 inflammasome as a chief instigator of obesity, contributing to local adipose tissue inflammation and insulin resistance. Environ Sci Pollut Res 28, 43102–43113 (2021). https://doi.org/10.1007/s11356-021-14904-4

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