Related Experiment Video

Updated: Jun 2, 2026

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
08:34

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

Follistatin and follistatin like-3 differentially regulate adiposity and glucose homeostasis

Melissa L Brown1, Lara Bonomi, Nathan Ungerleider

  • 1Pioneer Valley Life Science Institute, University of Massachusetts Amherst, Springfield, Massachusetts, USA.

Obesity (Silver Spring, Md.)
|May 7, 2011
PubMed

Insights

Follistatin (FST) and FSTL3 differentially regulate body composition and glucose homeostasis. Their combined loss in mice increases fat mass and insulin resistance, despite higher insulin levels and larger islets.

Area of Science:

  • Endocrinology
  • Metabolism
  • Molecular Biology

Background:

  • Transforming growth factor-β (TGF-β) superfamily ligands, including activin and myostatin, are key regulators of body composition, islet function, and glucose homeostasis.
  • The bioactivity of these ligands is tightly controlled by antagonists follistatin (FST) and FST-like 3 (FSTL3).

Purpose of the Study:

  • To investigate the distinct roles of FST and FSTL3 in regulating body composition, glucose homeostasis, and islet function.
  • To determine how FST and FSTL3 modulate activin and myostatin bioactivity in vivo.

Main Methods:

  • Generation of three distinct mouse genetic models: FSTL3 knockout (FSTL3 KO), a line expressing only the FST288 isoform (FST288-only), and a double mutant (2xM).
  • Assessment of body composition using quantitative nuclear magnetic resonance (qNMR).
  • Evaluation of glucose homeostasis, insulin levels, and pancreatic islet morphology and function across genotypes.

Main Results:

  • FST288-only males were lighter than wild-type (WT) mice; FSTL3 KO and 2xM males exhibited reduced perigonadal fat pad weights.
  • 2xM mice displayed increased whole-body fat mass and decreased lean mass, alongside elevated fasting glucose in older animals.
  • Despite increased serum insulin and pancreatic insulin content, 2xM mice showed insulin resistance and glucose intolerance. Islet size and β-cell proportion increased in FSTL3 KO and 2xM mice, but function was not enhanced.

Conclusions:

  • FST and FSTL3 play differential roles in regulating body composition and glucose metabolism.
  • Combined loss of FST and FSTL3 leads to increased adiposity and insulin resistance, characterized by compensatory hyperinsulinemia and altered islet structure without functional improvement.

More Related Videos

Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator06:08

Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator

Published on: May 19, 2023

Related Concept Videos

Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

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 the...
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...
Glucose Homeostasis: Regulation of Blood Glucose01:02

Glucose Homeostasis: Regulation of Blood Glucose

Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
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...
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are co-secreted in...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...