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primary topic: PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment

PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment
type: AcademicArticle
type: Article
abstract: Mycobacterium tuberculosis (Mtb) infection of the lungs, besides producing prolonged cough with mucus, also causes progressive fatigue and cachexia with debilitating loss of muscle mass. While anti-tuberculosis (TB) drug therapy is directed toward eliminating bacilli, the treatment regimen ignores the systemic pathogenic derailments that probably dictate TB-associated mortality and morbidity. Presently, it is not understood whether Mtb spreads to metabolic organs and brings about these impairments. Here, we show that Mtb creates a replication-conducive milieu of lipid droplets in hepatocytes by upregulating transcription factor PPARγ and scavenging lipids from the host cells. In hepatocytes, Mtb shields itself against the common anti-TB drugs by inducing drug-metabolizing enzymes. Infection of the hepatocytes in the in vivo aerosol mice model can be consistently observed post-week, 4 along with enhanced expression of PPARγ and drug-metabolizing enzymes. Moreover, histopathological analysis indeed shows the presence of Mtb in hepatocytes along with granuloma-like structures in human biopsied liver sections. Hepatotropism of Mtb during the chronic infectious cycle results in immuno-metabolic dysregulation that could magnify local and systemic pathogenicity, altering clinical presentations.
date: 2025-12
volume: 14
issue: RP1038
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository

eLife Sciences Publications, Ltd
type: Organization

Elife
type: Collection

Aakash Chandramouli
type: Person
given name: Aakash
family name: Chandramouli

Devram S Ghorpade
type: Person
given name: Devram S
family name: Ghorpade

Siddhesh S Kamat
type: Person
given name: Siddhesh S
family name: Kamat

Kritee Mehdiratta
type: Person
given name: Kritee
family name: Mehdiratta

Mohit Yadav
type: Person
given name: Mohit
family name: Yadav

Priya Sharma
type: Person
given name: Priya
family name: Sharma

Binayak Sarkar
type: Person
given name: Binayak
family name: Sarkar

Debasisa Mohanty
type: Person
given name: Debasisa
family name: Mohanty

Rajesh S Gokhale
type: Person
given name: Rajesh S
family name: Gokhale

Ashwani Kumar
type: Person
given name: Ashwani
family name: Kumar

Raman Deep Sharma
type: Person
given name: Raman Deep
family name: Sharma

Dhiraj Kumar
type: Person
given name: Dhiraj
family name: Kumar

Jyotsna Singh
type: Person
given name: Jyotsna
family name: Singh

Shweta Singh
type: Person
given name: Shweta
family name: Singh

HTML Summary of #3267 PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment
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primary topic: PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment