Lipotoxicity caused by excessive fat deposition in skeletal muscle cells is a characteristic of type II diabetes, heart disease and obesity. Defining how glucose stimulates this is therefore an important goal. Isabelle Guillet-Deniau and co-workers have now dissected the signalling mechanisms involved, using contracting myotubes derived from cultured muscle satellite cells (see p. 1937). They show that glucose treatment stimulates cells to take up glucose and upregulate expression of lipogenic enzymes. The authors then demonstrate that prior to this the cells synthesize and activate sterol-regulatory-element-binding protein 1c (SREBP-1c), a transcription factor that regulates cholesterol and fatty acid metabolism. Moreover, they show that knocking down SREBP-1c by RNAi blocks glucose-induced upregulation of lipogenic enzymes. Guillet-Deniau and co-workers go on to demonstrate that stimulation of SREBP-1c requires the JAK2/STAT3 signalling pathway but is independent of insulin, which is significant given that insulin can also activate SREBP-1c. Their results thus implicate SREBP-1c-dependent stimulation of lipogenesis by glucose in lipotoxicity. They also emphasize the effectiveness of RNAi in a biologically relevant muscle model.
Glucose signalling and lipotoxicity
Glucose signalling and lipotoxicity. J Cell Sci 15 April 2004; 117 (10): e1005. doi:
Download citation file:
Advertisement
Cited by
Introducing our new Editors
We welcome three new Editors to Journal of Cell Science - Robert Parton, Richa Rikhy and Simon Cook. You can read more about them in the Editorial from our Editor-in-Chief Michael Way.
2024 Journal Meeting 'Diversity and Evolution in Cell Biology'
Registration is open for our 2024 Journal Meeting Diversity and Evolution in Cell Biology, which aims to bring together evolutionary biologists and cell biologists investigating diverse aspects of cellular physiology. Final registration deadline: 3 May 2024.
Workshop: Physics of the Early Embryonic Cell Divisions
Early-career researchers interested in the roles of nuclear lipids, apply now for one of the ten funded places at this Workshop, which will take place 11-14 November 2024. Application deadline: 17 May.
Reasons to submit to Journal of Cell Science
There are many benefits to publishing in Journal of Cell Science - read more about why you should choose JCS or visit our submission page now.
Propose a new Workshop for 2026
We are now accepting proposals for our 2026 Workshops programme. We aim to be responsive to the community and open to novel initiatives, so if you have a new idea for a biological workshop that you feel would work well, please apply. Applications deadline: 19 July 2024.