Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Yeh, YS; Evans, TD; Iwase, M; Jeong, SJ; Zhang, X; Liu, Z; Park, A; Ghasemian, A; Dianati, B; Javaheri, A; Kratky, D; Kawarasaki, S; Goto, T; Zhang, H; Dutta, P; Schopfer, FJ; Straub, AC; Cho, J; Lodhi, IJ; Razani, B.
Identification of lysosomal lipolysis as an essential noncanonical mediator of adipocyte fasting and cold-induced lipolysis.
J Clin Invest. 2025; 135(6):
Doi: 10.1172/JCI185340
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- Co-Autor*innen der Med Uni Graz
- Kratky Dagmar
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- Abstract:
- Adipose tissue lipolysis is the process by which triglycerides in lipid stores are hydrolyzed into free fatty acids (FFAs), serving as fuel during fasting or cold-induced thermogenesis. Although cytosolic lipases are considered the predominant mechanism of liberating FFAs, lipolysis also occurs in lysosomes via lysosomal acid lipase (LIPA), albeit with unclear roles in lipid storage and whole-body metabolism. We found that adipocyte LIPA expression increased in adipose tissue of mice when lipolysis was stimulated during fasting, cold exposure, or β-adrenergic agonism. This was functionally important, as inhibition of LIPA genetically or pharmacologically resulted in lower plasma FFAs under lipolytic conditions. Furthermore, adipocyte LIPA deficiency impaired thermogenesis and oxygen consumption and rendered mice susceptible to diet-induced obesity. Importantly, lysosomal lipolysis was independent of adipose triglyceride lipase, the rate-limiting enzyme of cytosolic lipolysis. Our data suggest a significant role for LIPA and lysosomal lipolysis in adipocyte lipid metabolism beyond classical cytosolic lipolysis.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Lipolysis - administration & dosage
- Lysosomes - metabolism
- Mice - administration & dosage
- Cold Temperature - administration & dosage
- Fasting - metabolism
- Adipocytes - metabolism
- Sterol Esterase - metabolism, genetics
- Thermogenesis - administration & dosage
- Mice, Knockout - administration & dosage
- Male - administration & dosage
- Obesity - metabolism, genetics
- Fatty Acids, Nonesterified - metabolism
- Mice, Inbred C57BL - administration & dosage