PMID- 33569904 OWN - NLM STAT- MEDLINE DCOM- 20210317 LR - 20211204 IS - 1467-789X (Electronic) IS - 1467-7881 (Print) IS - 1467-7881 (Linking) VI - 22 IP - 4 DP - 2021 Apr TI - Amino acid sensing pathway: A major check point in the pathogenesis of obesity and COVID-19. PG - e13221 LID - 10.1111/obr.13221 [doi] LID - e13221 AB - Obesity and obesogenic comorbidities have been associated with COVID-19 susceptibility and mortality. However, the mechanism of such correlations requires an in-depth understanding. Overnutrition/excess serum amino acid profile during obesity has been linked with inflammation and reprogramming of translational machinery through hyperactivation of amino acid sensor mammalian target of rapamycin (mTOR), which is exploited by SARS-CoV-2 for its replication. Conversely, we have shown that the activation of general control nonderepressible 2 (GCN2)-dependent amino acid starvation sensing pathway suppresses intestinal inflammation by inhibiting the production of reactive oxygen species (ROS) and interleukin-1 beta (IL-1beta). While activation of GCN2 has shown to mitigate susceptibility to dengue infection, GCN2 deficiency increases viremia and inflammation-associated pathologies. These findings reveal that the amino acid sensing pathway plays a significant role in controlling inflammation and viral infections. The current fact is that obesity/excess amino acids/mTOR activation aggravates COVID-19, and it might be possible that activation of amino acid starvation sensor GCN2 has an opposite effect. This article focuses on the amino acid sensing pathways through which host cells sense the availability of amino acids and reprogram the host translation machinery to mount an effective antiviral response. Besides, how SARS-CoV-2 hijack and exploit amino acid sensing pathway for its replication and pathogenesis is also discussed. CI - (c) 2021 World Obesity Federation. FAU - Philips, Aradhana Mariam AU - Philips AM AUID- ORCID: 0000-0002-6102-970X AD - Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, India. FAU - Khan, Nooruddin AU - Khan N AUID- ORCID: 0000-0001-6356-5023 AD - Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India. LA - eng GR - 34/11/2019-T/F/NANO/BMS/Indian Council of Medical Research (ICMR)/ GR - DBT/04/0401/2019/01546/Department of Biotechnology-Biotechnology Industry Research Assistance Council (DBT-BIRAC)/ GR - UoH/IoE/RC1/RC1-20-017/Institutions of Eminence (IoE)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20210210 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 0 (Amino Acids) RN - EC 2.4.1.- (GCNT2 protein, human) RN - EC 2.4.1.- (N-Acetylhexosaminyltransferases) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) SB - IM MH - Amino Acids/*metabolism MH - Angiotensin-Converting Enzyme 2/metabolism MH - COVID-19/*epidemiology/physiopathology MH - Comorbidity MH - Humans MH - Inflammation MH - N-Acetylhexosaminyltransferases/*physiology MH - Obesity/*epidemiology/physiopathology MH - Protein Biosynthesis/physiology MH - *SARS-CoV-2/physiology MH - TOR Serine-Threonine Kinases/physiology MH - Virus Replication/physiology PMC - PMC7995014 OTO - NOTNLM OT - COVID-19 OT - SARS-CoV-2 OT - amino acid sensor GCN2 OT - comorbidities OT - obesity OT - pro-inflammatory cytokine COIS- No conflict of interest to disclose. EDAT- 2021/02/12 06:00 MHDA- 2021/03/18 06:00 PMCR- 2021/03/26 CRDT- 2021/02/11 06:00 PHST- 2020/11/27 00:00 [received] PHST- 2021/01/15 00:00 [revised] PHST- 2021/01/22 00:00 [accepted] PHST- 2021/02/12 06:00 [pubmed] PHST- 2021/03/18 06:00 [medline] PHST- 2021/02/11 06:00 [entrez] PHST- 2021/03/26 00:00 [pmc-release] AID - OBR13221 [pii] AID - 10.1111/obr.13221 [doi] PST - ppublish SO - Obes Rev. 2021 Apr;22(4):e13221. doi: 10.1111/obr.13221. Epub 2021 Feb 10.