A Feedback Loop Governs the Relationship Between Lipid Metabolism and Longevity

Overview

Journal Elife

Specialty Biology

Date 2020 Oct 20

PMID 33078707

Citations 11

Authors

Nicole K Littlejohn

Nicolas Seban

Chung-Chih Liu

Supriya Srinivasan

Affiliations

Soon will be listed here.

Abstract

The relationship between lipid metabolism and longevity remains unclear. Although fat oxidation is essential for weight loss, whether it remains beneficial when sustained for long periods, and the extent to which it may attenuate or augment lifespan remain important unanswered questions. Here, we develop an experimental handle in the model system, in which we uncover the mechanisms that connect long-term fat oxidation with longevity. We find that sustained β-oxidation via activation of the conserved triglyceride lipase ATGL-1, triggers a feedback transcriptional loop that involves the mito-nuclear transcription factor ATFS-1, and a previously unknown and highly conserved repressor of ATGL-1 called HLH-11/AP4. This feedback loop orchestrates the dual control of fat oxidation and lifespan, and shields the organism from life-shortening mitochondrial stress in the face of continuous fat oxidation. Thus, we uncover one mechanism by which fat oxidation can be sustained for long periods without deleterious effects on longevity.

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