Transcriptional Regulation of Glucose and Lipid Metabolism

The coordinated control of carbohydrate and lipid pathways is achieved through nutrient- and hormone-sensitive transcriptional programmes in key metabolic tissues, principally the liver and adipose depots. Central to this regulation are transcription factors that sense intracellular metabolites or endocrine cues and direct the expression of enzymes involved in glycolysis, gluconeogenesis, de novo lipogenesis and fatty acid oxidation. Carbohydrate-responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c) integrate signals from glucose and insulin, respectively, to synchronise the transcription of genes encoding glycolytic and lipogenic enzymes. Additional factors such as TCF7L2 and MLX adjust the balance between lipid synthesis and utilisation in response to dietary composition and genetic variation. Dysregulation of these transcriptional networks underlies metabolic diseases including non-alcoholic fatty liver disease, type 2 diabetes and dyslipidaemia. Advancements in mechanistic insight have revealed how post-translational modifications, chromatin remodelling and co-factor recruitment refine the activity of master regulators, paving the way for targeted interventions that modulate energy homeostasis and ameliorate disease risk on a global scale.

Research from Nature Portfolio

Recent studies have shown that excessive dietary fructose drives a ChREBP-dependent transcriptional programme that upregulates the manganese exporter Slc30a10 in hepatocytes, leading to reduced hepatic manganese content and impaired arginase-mediated ammonia detoxification. Genetic ablation of ChREBP or its target Slc30a10 restores manganese homeostasis and ammonia clearance, highlighting a nutrient-responsive axis that connects carbohydrate intake to trace metal balance and nitrogen metabolism. This discovery not only broadens the functional scope of metabolic transcription factors but also suggests dietary modulation as a strategy to prevent hyperammonaemia in liver dysfunction.

Transcriptional Regulation of Glucose and Lipid Metabolism publication trend

The graph below shows the total number of articles in transcriptional regulation of glucose and lipid metabolism across all publications each year (not limited to Nature Index journals).

Technical terms

Carbohydrate-responsive element-binding protein (ChREBP): A transcription factor activated by glucose metabolites that induces genes for glycolysis and de novo lipogenesis.

Sterol regulatory element-binding protein-1c (SREBP-1c): An insulin-responsive transcription factor that promotes fatty acid synthesis.

De novo lipogenesis (DNL): The metabolic pathway by which carbohydrates are converted into fatty acids for lipid synthesis.

Transcription factor: A protein that binds to specific DNA sequences to regulate gene expression.

Hepatocytes: The primary functional cells of the liver responsible for metabolic homeostasis.

References

1. Fructose overconsumption impairs hepatic manganese homeostasis and ammonia disposal. Nature Communications (2023).
2. MLX plays a key role in lipid and glucose metabolism in humans: Evidence from in vitro and in vivo studies. Metabolism (2023).
3. Tcf7l2 in hepatocytes regulates de novo lipogenesis in diet-induced non-alcoholic fatty liver disease in mice. Diabetologia (2023).
4. Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice[S]. Journal of Lipid Research (2018).