Feeding induced changes in the hypothalamic transcriptome
Maria Rita De Giorgio1, Mayumi Yoshioka, Jonny St-Amand
1Functional Genomics Laboratory, Molecular Endocrinology and Oncology Research Center, Laval University Medical Center and Department of Anatomy and Physiology, Laval University, Québec, Canada.
Summary
This study reveals how high-fat (HF) and low-fat (LF) meals rapidly alter hypothalamic gene expression in mice. Specific genes involved in energy intake regulation were identified, with three uniquely modulated by HF diets.
Area of Science:
- Neuroscience
- Molecular Biology
- Metabolism
Background:
- Obesity is a complex disorder requiring comprehensive management strategies.
- Understanding the rapid molecular signals in the hypothalamus is crucial for energy intake control.
Purpose of the Study:
- To investigate hypothalamic gene expression changes following high-fat (HF) and low-fat (LF) meal ingestion in mice.
- To identify genes mediating the rapid hypothalamic control of energy intake.
Main Methods:
- Mice were fasted and then fed either HF or LF diets ad libitum.
- Hypothalamic tissue was sampled 3 hours post-meal for gene expression analysis using Serial Analysis of Gene Expression (SAGE).
Main Results:
- Over 65,000 unique gene tags were analyzed, revealing twelve transcripts regulated by food intake.
- Identified transcripts included those involved in mitochondrial function, protein transport, cellular pH control, and epigenetic regulation.
- Five potentially novel transcripts were also found to be differentially modulated.
Conclusions:
- Key genes regulating hypothalamic circuits involved in the early response to food intake were identified.
- Three specific genes were found to be uniquely modulated by high-fat intake, suggesting a role in HF-driven energy regulation.
Related Concept Videos
Regulation of Food Intake
Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
Hypothalamic-Pituitary Axis
The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
Target Cell Response to Hormones
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Regulation of Hormone Secretion
Regulation of hormone secretion is a finely tuned orchestration driven by various types of stimuli, encompassing neural, humoral, and hormonal signals. Environmental cues instigate neural stimuli, where action potentials traverse nerve fibers to reach their designated targets. An illustrative scenario is the body's response to stress, wherein the sympathetic nervous system releases epinephrine from the adrenal glands, inducing the well-known 'fight or flight' reaction.
Humoral stimuli,...
Humoral stimuli,...
Feedback Loops
In most cases, excessive hormone production is prevented by negative feedback—a loop that starts with a stimulus inducing the release of a particular substance, like a hormone, to maintain a certain level before triggering a signal that results in a decrease in further release of the hormone.
Hormones of the Pituitary Gland
The small, pea-sized pituitary gland is located at the base of the brain. It is crucial in regulating various bodily functions, from growth to reproduction. The gland is divided into the anterior lobe and the posterior lobe. The secretory cell clusters in the pars distalis of the anterior pituitary lobe are controlled by hypothalamic regulators and synthesize six primary hormones.
The most abundantly secreted hormone from the anterior lobe is the growth hormone, which controls overall growth by...
The most abundantly secreted hormone from the anterior lobe is the growth hormone, which controls overall growth by...


