SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology
Abstract
Cellular lipid metabolism and homeostasis are controlled by sterol regulatory-element binding proteins (SREBPs). In addition to performing canonical functions in the transcriptional regulation of genes involved in the biosynthesis and uptake of lipids, genome-wide system analyses have revealed that these versatile transcription factors act as important nodes of convergence and divergence within biological signalling networks. Thus, they are involved in myriad physiological and pathophysiological processes, highlighting the importance of lipid metabolism in biology. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signalling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. In addition, SREBPs are implicated in numerous pathogenic processes such as endoplasmic reticulum stress, inflammation, autophagy and apoptosis, and in this way, they contribute to obesity, dyslipidaemia, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic kidney disease, neurodegenerative diseases and cancers. This Review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ and organism levels.
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Cholesterol biosynthesis and lipid efflux machinery are regulated via LXR/RXR complex activation; when intracellular cholesterol is increased, LXR/RXR increases ABCA1 expression to induce lipid efflux, APOE expression, and inhibition of SREBP activation.
“Cholesterol biosynthesis and lipid efflux machinery are regulated via LXR and retinoid X receptor (RXR) complex activation; when intracellular cholesterol is increased, LXR/RXR increases ABCA1 expression to induce lipid efflux, APOE expression, and inhibition of SREBP activation (Shimano and Sato, 2017).”
From APOE2, E3, and E4 differentially modulate cellular homeostasis, cholesterol metabolism, and inflammatory response in isogenic iPSC-derived astrocytes (2022) · cites this paper as Shimano and Sato, 2017
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- Authors
- Shimano, H., & Sato, R.
- Affiliations
- University of Tsukuba (JP)
- Japan Agency for Medical Research and Development (JP)
- Corresponding author
- Shimano, Hitoshi
- Venue
- Nature Reviews Endocrinology
- Published
- 2017-08-29
- Volume
- 13
- Issue
- 12
- Pages
- 710-730
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W2752390584
- Cited by
- 1,174
- References
- 17
- Citations by year
- 2026: 133 · 2025: 199 · 2024: 171 · 2023: 169 · 2022: 148 · 2021: 146 · 2020: 113 · 2019: 52 · 2018: 39 · 2017: 3 · 2013: 1
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (17H06395)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- SREBP, lipid metabolism, lipid homeostasis, transcriptional regulation, endoplasmic reticulum stress, inflammation, autophagy, apoptosis, obesity, dyslipidemia, diabetes mellitus, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic kidney disease, neurodegenerative diseases, cancer
- MeSH terms
- Cell Nucleus, Cells, Diabetes Mellitus, Energy Metabolism, Homeostasis, Humans, Neoplasms, Nutritional Physiological Phenomena, Obesity, Signal Transduction, Neurodegenerative Diseases, Cell Proliferation, Dyslipidemias, Lipid Metabolism, Renal Insufficiency, Chronic, Sterol Regulatory Element Binding Proteins, Non-alcoholic Fatty Liver Disease
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