Seeing is believing: visualizing spatiotemporal lipophagic flux in vivo with the tfLiveDrop reporter mice.

Abstract

Lipophagy, the selective autophagic degradation of lipid droplets (LDs), is central to cellular lipid homeostasis, yet its dynamic regulation in living organisms has remained largely unobservable in real time. To overcome this barrier, we recently developed the mCherry‑eGFP‑LiveDrop (tfLiveDrop) reporter mice, in which a pH‑sensitive tandem fluorescent probe targeted to LDs via the GPAT4‑derived LiveDrop domain enables real‑time, single‑cell visualization of lipophagic flux in vivo. Using tfLiveDrop mice, we uncovered pronounced organ heterogeneity in basal lipophagy, identified an organ‑specific lipophagic inhibition in type 2 diabetes, and revealed a previously unrecognized developmentally programmed lipophagy induction that drives renal metabolic maturation. Together, these findings demonstrate that tfLiveDrop is a sensitive and versatile reporter for in vivo lipophagy research.