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Updated: May 3, 2026
Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol
Published on: March 25, 2020
Niemann-Pick disease type C2 protein induces triglyceride accumulation in silkworm and mammalian cell lines
Tatsuo Adachi1, Kenichi Ishii1, Yasuhiko Matsumoto1
1*Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Abstract:
Silkworm haemolymph induced both the cessation of growth and an increase in triglyceride (triacylglycerol) storage in BmN4 cells. We purified the growth inhibitory factor from the silkworm haemolymph and identified this protein as the Bombyx mori PP (promoting protein), an orthologue of NPC2 (Niemann-Pick disease type C2) protein. Recombinant silkworm NPC2 inhibited cellular proliferation and increased triglyceride accumulation in BmN4 cells. Injection of either the recombinant protein or antiserum of NPC2 into living silkworms increased or decreased respectively triglyceride levels in the fat body. A mutation that depletes the cholesterol-binding capacity did not abolish the activity of NPC2. We further revealed that NPC2 induced the phosphorylation of AMPK (AMP-activated protein kinase) and that an AMPK inhibitor suppressed NPC2-dependent triglyceride accumulation. These findings suggest that NPC2 induces triglyceride accumulation via the activation of AMPK independently of its cholesterol-binding capacity in the silkworm.
Insights
Silkworm Bombyx mori PP (promoting protein), an NPC2 orthologue, halts growth and boosts triglyceride storage by activating AMPK, independent of cholesterol binding.
Area of Science:
- Biochemistry
- Molecular Biology
- Insect Physiology
Background:
- Silkworm haemolymph contains factors influencing cellular processes.
- Triglyceride accumulation is a key metabolic event in insects.
Purpose of the Study:
- To identify the growth inhibitory factor in silkworm haemolymph.
- To elucidate the mechanism by which this factor affects triglyceride storage.
Main Methods:
- Purification and identification of the growth inhibitory factor.
- Use of recombinant silkworm NPC2 in cell culture (BmN4 cells).
- In vivo studies in silkworms involving protein injection and antiserum administration.
- Biochemical assays to assess protein activity and signaling pathways (AMPK phosphorylation).
Main Results:
- The growth inhibitory factor was identified as Bombyx mori PP, an orthologue of NPC2.
- Recombinant silkworm NPC2 inhibited proliferation and increased triglyceride accumulation in BmN4 cells.
- NPC2 activated AMP-activated protein kinase (AMPK) phosphorylation, which was essential for triglyceride accumulation.
- NPC2's cholesterol-binding capacity was not required for its activity.
Conclusions:
- Bombyx mori NPC2 induces triglyceride accumulation through AMPK activation.
- This process is independent of NPC2's cholesterol-binding ability.
- NPC2 plays a significant role in regulating lipid metabolism in silkworms.
