Related Experiment Video

Updated: Mar 27, 2026

Manipulation of Rhythmic Food Intake in Mice Using a Custom-Made Feeding System
07:34

Manipulation of Rhythmic Food Intake in Mice Using a Custom-Made Feeding System

Published on: December 16, 2022

3.0K

FGF21 regulates metabolism and circadian behavior by acting on the nervous system

Angie L Bookout1, Marleen H M de Groot, Bryn M Owen

  • 11] Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. [2] Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Nature Medicine
|August 13, 2013
PubMed

Insights

Fibroblast growth factor 21 (FGF21) acts as a starvation signal. Its effects on metabolism and behavior are mediated by the nervous system through β-Klotho in the brain.

Area of Science:

  • Metabolic signaling
  • Neuroendocrinology
  • Hormone action

Background:

  • Fibroblast growth factor 21 (FGF21) is a hepatokine regulating metabolism and growth, acting as a starvation signal.
  • FGF21 signaling requires FGF receptors (FGFRs) and β-Klotho, a co-receptor enriched in metabolic tissues.
  • The precise sites of action for FGF21's diverse systemic effects remain largely unknown.

Purpose of the Study:

  • To investigate the role of the nervous system in mediating FGF21's physiological and pharmacological actions.
  • To identify the specific brain regions critical for FGF21's adaptive starvation responses.
  • To elucidate the mechanism by which FGF21 influences metabolism, behavior, and hormone levels.

Main Methods:

  • Utilized genetically modified mice lacking β-Klotho (Klb) specifically in the suprachiasmatic nucleus and dorsal vagal complex.
  • Assessed FGF21-induced changes in systemic glucocorticoid levels, physical activity, and circadian behavior.
  • Evaluated the impact of regional β-Klotho deficiency on FGF21's metabolic, insulin, and growth effects.

Main Results:

  • FGF21 was found to increase systemic glucocorticoid levels, suppress physical activity, and alter circadian behavior, mimicking starvation responses.
  • These FGF21-mediated effects were dependent on β-Klotho expression within the suprachiasmatic nucleus and dorsal vagal complex.
  • Mice with targeted β-Klotho gene deletion in these brain regions were refractory to FGF21's systemic, metabolic, insulin, and growth-related actions.

Conclusions:

  • The nervous system, particularly the hypothalamus and hindbrain, plays a critical role in mediating FGF21's diverse physiological effects.
  • β-Klotho expression in specific brain regions is essential for FGF21 to regulate metabolism, behavior, and adaptive starvation responses.
  • These findings highlight a novel neuro-centric mechanism for FGF21 action, expanding our understanding of metabolic control.

More Related Videos

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells11:56

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells

Published on: September 28, 2017

10.5K
Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures06:53

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Published on: November 11, 2016

8.9K

Related Concept Videos

Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.7K
Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

No description available
2.5K
Regulation of Food Intake01:30

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...
3.1K
Regulation of Metabolism01:19

Regulation 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...
12.3K
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

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...
8.4K
Regulation of the Digestive System01:25

Regulation of the Digestive System

Digestive activity regulation hinges on three primary components. Activation is prompted by a multitude of mechanical and chemical indicators, primarily detected by receptors within the stomach and intestines' walls. These receptors predominantly respond to factors such as mechanical stretching of the organ walls, changes in pH and osmolarity, and the presence of digesting materials and their by-products.
The effectors in this regulation system are glands and smooth muscles. Activation of...
3.8K