Related Experiment Video
Updated: May 30, 2026
07:34
Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability
Lilia G Noriega1, Jérôme N Feige, Carles Canto
1Ecole Polytechnique Fédérale de Lausanne, Laboratory of Integrative and Systems Physiology and Nestlé Chair in Energy Metabolism, 1015 Lausanne, Switzerland.
EMBO Reports
|August 13, 2011
Summary
SIRT1, a key metabolic regulator, is controlled by nutrient availability. Its expression is upregulated during fasting via CREB activation and repressed by ChREBP when nutrients are abundant, highlighting its role as a metabolic checkpoint.
Area of Science:
- Metabolic regulation
- Molecular biology
- Gene expression control
Background:
- SIRT1 (nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase) is a critical metabolic regulator activated by energy stresses like fasting and calorie restriction.
- SIRT1 activation during fasting involves increased NAD(+)/NADH ratio and upregulation of SIRT1 at mRNA and protein levels in metabolic tissues.
Purpose of the Study:
- To elucidate the transcriptional mechanisms controlling SIRT1 expression in response to nutrient availability.
- To identify the key transcription factors involved in regulating SIRT1 expression under different metabolic conditions.
Main Methods:
- Analysis of SIRT1 mRNA and protein levels under varying nutrient conditions.
- Investigation of the roles of cyclic AMP response-element-binding protein (CREB) and carbohydrate response-element-binding protein (ChREBP) in SIRT1 regulation.
- Systemic and tissue-specific expression studies.
Main Results:
- SIRT1 expression is systemically controlled by CREB activation during low nutrient availability (fasting).
- ChREBP represses SIRT1 expression in the absence of energetic stress (nutrient abundance).
- Nutrient availability tightly controls SIRT1 expression at the transcriptional level.
Conclusions:
- SIRT1 acts as a crucial metabolic checkpoint, linking cellular energy status to transcriptional programs.
- The findings reveal a coordinated transcriptional control of SIRT1 by nutrient-sensing pathways involving CREB and ChREBP.
- Understanding SIRT1 regulation provides insights into metabolic homeostasis and adaptation to nutritional cues.
Related Concept Videos
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
01:58Cell Specific Gene Expression
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:19Regulation of Metabolism
Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
01:28Global Regulatory Systems
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...