Related Experiment Video
Updated: Aug 15, 2025
05:45
Experimental Approach to Examine Leptin Signaling in the Carotid Bodies and its Effects on Control of Breathing
Published on: October 25, 2019
6.0K
Hypothalamic Grb10 enhances leptin signalling and promotes weight loss
Hailan Liu1,2, Yang He2, Juli Bai1,3
1National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
Nature Metabolism
|January 2, 2023
Summary
Growth factor receptor-bound protein 10 (Grb10) enhances leptin signaling in the hypothalamus. Modulating Grb10 in AgRP and POMC neurons impacts body weight and energy homeostasis, identifying it as a key leptin sensitizer.
Area of Science:
- Neuroscience
- Metabolism
- Molecular Biology
Background:
- Leptin regulates appetite and energy expenditure via hypothalamic neurons.
- Intracellular mechanisms of leptin signaling require further elucidation.
Purpose of the Study:
- To investigate the role of growth factor receptor-bound protein 10 (Grb10) in central leptin signaling.
- To determine how Grb10 modulates energy homeostasis through AgRP and POMC neurons.
Main Methods:
- Investigated Grb10 interaction with the leptin receptor.
- Utilized genetic ablation and overexpression of Grb10 in AgRP and POMC neurons in mice.
- Examined effects on body weight, appetite, and energy expenditure.
- Analyzed leptin-induced ion channel currents in neurons.
Main Results:
- Grb10 interacts with the leptin receptor and enhances leptin signaling.
- Grb10 ablation in AgRP neurons increases weight gain; overexpression reduces it.
- Grb10 deletion in POMC neurons exacerbates diet-induced obesity; overexpression attenuates it.
- Grb10 modulates leptin's effects on neuronal activity via ion channels.
Conclusions:
- Grb10 acts as a leptin sensitizer, enhancing leptin's effects on AgRP and POMC neurons.
- Grb10 plays a critical role in maintaining energy homeostasis by fine-tuning leptin sensitivity.
Related Concept Videos
01:30Regulation of Food Intake
314
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...
314
01:24Glucagon-like Receptor Agonists
383
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
383
01:16Hormones Regulating Blood Glucose
3.6K
Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
In addition to accelerating glucose uptake and utilization, insulin has...
3.6K
01:24Obesity
576
The Body Mass Index (BMI) is a numerical value derived from a person's weight and height, used to categorize individuals into weight ranges. It is calculated using the formula: weight in kilograms divided by height in meters squared. Obesity is a health condition characterized by excessive accumulation of adipose tissue that poses health risks, often diagnosed with a BMI ≥ 30. This excess fat storage occurs when surplus dietary calories are converted into triglycerides and stored in...
576
01:37Hypothalamic-Pituitary Axis
61.1K
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.
61.1K
01:19Regulation of Metabolism
9.6K
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...
9.6K