Abstract
How trafficking pathways and organelle abundance adapt in response to metabolic and physiological changes is still mysterious, although a few transcriptional regulators of organellar biogenesis have been identified in recent years. We previously found that the Wnt signaling directly controls lipid droplet formation, linking the cell storage capacity to the established functions of Wnt in development and differentiation. In the present paper, we report that Wnt-induced lipid droplet biogenesis does not depend on the canonical TCF/LEF transcription factors. Instead, we find that TFAP2 family members mediate the pro-lipid droplet signal induced by Wnt3a, leading to the notion that the TFAP2 transcription factor may function as a 'master' regulator of lipid droplet biogenesis.
Highlights
Cellular adaptation to a changing local environment is imperative for survival and proliferation
We report that the biogenesis of lipid droplets induced by Wnt signaling does not depend on the canonical TCF/LEF transcription factors
We found that many candidate transcription factors known to function in both lipid metabolism and adipogenesis were influenced by Wnt3a-treament and fatty acid perturbation (Figure 2—source data 2), including TFAP2A (p-value Wnt3a treatment: 3.5 Â 10À9; p-value fatty acid perturbation: 4.8 Â 10À4)
Summary
Cellular adaptation to a changing local environment is imperative for survival and proliferation This is effected through a collection of sensing and signaling pathways that integrate information about the local environment and induce the requisite changes in various cellular programs that control organelle abundance and function, through multiple routes, including the modulation of transcription. While a major function of lipid droplets is clearly as the storehouse of triglycerides and sterol esters, the diversity and variation of this organelle likely reflect the number of reported alternate functions of lipid droplets such as regulation of inflammation, general metabolism, and host-pathogen interplay (Barisch and Soldati, 2017; Melo and Weller, 2016; Konige et al, 2014). Despite the recognized importance of this organelle in health and disease, little is known of the signaling systems or proximal transcriptional regulators that control lipid droplet biogenesis, function and turnover in cells
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