Tissue-specific regulation of PNPLA3 promotes lipid remodeling in response to dietary and environmental challenges: Tissue-specific PNPLA3 lipid remodeling - PubMed

3 days ago

PNPLA3(I148M) is the strongest genetic risk factor for steatotic liver disease (SLD), but its functional role and tissue-specific regulation remain unclear.
Pnpla3 mRNA levels are significantly higher in mouse adipose tissue than liver, yet its role in adipose tissue is not well understood.
Feeding strongly increased PNPLA3 levels in liver at thermoneutrality, while cold exposure or β3-adrenergic stimulation increased PNPLA3 >19-fold in brown adipose tissue (BAT).
In BAT, adrenergic signaling via cAMP/PKA and PI3K/AKT elevated PNPLA3 by reducing proteasomal degradation.
PNPLA3 expression correlated with depletion of TG-long-chain polyunsaturated fatty acids (TG-LCPUFAs) in both liver and BAT, suggesting a role in lipid remodeling.
The study reveals tissue- and context-specific regulation of PNPLA3, linking its expression to TG-LCPUFAs levels and suggesting a role in adapting to metabolic stress.
Modulation of PNPLA3 turnover and its impact on LCPUFAs remodeling emerges as a potential therapeutic strategy for regulating lipid homeostasis in SLD.

Hasty Briefsbeta