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GSE53590
Mus musculus
8 Downloadable Samples
Description
Diet-induced obesity (DIO) is rapidly becoming a global health problem, particularly as Westernization of emerging nations continues. Currently, one third of adult Americans are considered obese and, if current trends continue, >90% of US citizens are predicted to be affected by 2050. However, efforts to fight this epidemic have not yet produced sound solutions for prevention or treatment. Our studies reveal a balanced and chronobiological relationship between food consumption, daily variation in gut microbial evenness and function, basomedial hypothalamic circadian clock (CC) gene expression, and key hepatic metabolic regulatory networks , including CC and nuclear receptors (NR), that is are essential for metabolic homeostasis. Western diets high in saturated fats dramatically alter diurnal variation in microbial composition and function, which in turn lead to uncoupling of the hepatic CC and NR networks from central CC control in ways that offset the timing and types of regulatory factors directing metabolic function. These signals include microbial metabolites such as short chain fatty acids (SCFAs) and hydrogen sulfide (H2S) that can directly regulate or disrupt metabolic networks of the hepatocyte. Our study therefore provides insights into the complex and dynamic relationships between diet, gut microbes, and the host that are critical for maintenance of health. Perturbations of this constellation of processes, in this case by diet-induced dysbiosis and its metabolomic signaling, can potentially promote metabolic imbalances and disease. This knowledge opens up many possibilities for novel therapeutic and interventional strategies to treat and prevent DIO, ranging from the manipulation of gut microbial function to pharmacological targeting of host pathways to restore metabolic balance.
Publication Title
Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 1 Downloadable Sample
Description
Key regulators of septum formation between the left and right ventricle in mammals, including the transcription factors TXB5 and PITX2, feature loss-of-function phenotypes that affect development of the two-chambered zebrafish heart, suggesting
Publication Title
Generating and evaluating a ranked candidate gene list for potential vertebrate heart field regulators.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Obesity is often associated with a low-grade systemic inflammation state that contributes to the development of insulin resistance and atherosclerotic complications. This is usually coupled with increased macrophage infiltration in the adipose tissue and a defect in adipocyte differentiation that results in accumulation of hypertrophic fat cells characterized by a deregulated pattern of adipokine expression. Here we show that knockdown of histone demethylase lsd1 in 3T3-L1 preadipocytes results in defective adipogenesis and derepression of an inflammatory program in these cells.
Publication Title
Histone demethylase KDM1A represses inflammatory gene expression in preadipocytes.
Sample Metadata Fields
Specimen part, Cell line
View Samples