title: PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment
creator: Sarkar, Binayak
creator: Singh, Jyotsna
creator: Yadav, Mohit
creator: Sharma, Priya
creator: Sharma, Raman Deep
creator: Singh, Shweta
creator: Chandramouli, Aakash
creator: Mehdiratta, Kritee
creator: Kumar, Ashwani
creator: Kamat, Siddhesh S
creator: Ghorpade, Devram S
creator: Mohanty, Debasisa
creator: Kumar, Dhiraj
creator: Gokhale, Rajesh S
description: 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.
publisher: eLife Sciences Publications, Ltd
date: 2025-12
type: Article
type: NonPeerReviewed
identifier:   Sarkar, Binayak and Singh, Jyotsna and Yadav, Mohit and Sharma, Priya and Sharma, Raman Deep and Singh, Shweta and Chandramouli, Aakash and Mehdiratta, Kritee and Kumar, Ashwani and Kamat, Siddhesh S and Ghorpade, Devram S and Mohanty, Debasisa and Kumar, Dhiraj and Gokhale, Rajesh S  (2025) PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment.  Elife, 14 (RP1038).       
relation: http://crdd.osdd.net/open/3267/