Treating diabetes and obesity with an FGF21-mimetic antibody activating the βKlotho/FGFR1c receptor complex

Related Experiment Video

Updated: May 16, 2026

White and Brown Adipose Grafts: An Approach to Correct Reproductive, Metabolic, and Renal Deficits in Black and Tan Brachyury (BTBR) Obese Mice
06:16

White and Brown Adipose Grafts: An Approach to Correct Reproductive, Metabolic, and Renal Deficits in Black and Tan Brachyury (BTBR) Obese Mice

Published on: September 9, 2025

Ian N Foltz1, Sylvia Hu, Chadwick King

  • 1Amgen British Columbia, 7990 Enterprise Street, Burnaby, British Columbia V5A1V7, Canada.

Science Translational Medicine
|December 1, 2012
PubMed

Insights

A novel antibody, mimAb1, mimics Fibroblast Growth Factor 21 (FGF21) effects, reducing weight and improving metabolism in obese monkeys. This antibody offers a potential new therapy for diabetes and obesity by targeting the FGFR1c receptor complex.

Area of Science:

  • Metabolic research
  • Endocrinology
  • Pharmacology

Background:

  • Fibroblast Growth Factor 21 (FGF21) is a key metabolic regulator with therapeutic potential for diabetes and obesity.
  • FGF21 exerts its effects via interaction with the βKlotho co-receptor and FGF receptors (FGFRs).

Purpose of the Study:

  • To develop and evaluate a monoclonal antibody (mimAb1) that activates FGF21 signaling pathways.
  • To investigate the role of FGFR1c and adipose tissue in FGF21-mediated metabolic improvements.

Main Methods:

  • Development of mimAb1, a high-affinity antibody targeting the βKlotho/FGFR1c complex.
  • Administration of mimAb1 to obese cynomolgus monkeys to assess metabolic effects.
  • Evaluation of FGF21 efficacy in mice with adipose-selective FGFR1 knockout.

Main Results:

  • MimAb1 induced FGF21-like metabolic benefits in obese monkeys, including weight loss and improved glucose and lipid profiles.
  • Mice lacking adipose FGFR1 were unresponsive to FGF21, highlighting FGFR1c's essential role.
  • Fat tissue was identified as a critical target for FGF21 and mimAb1 action.

Conclusions:

  • MimAb1 effectively mimics FGF21's metabolic actions and represents a promising therapeutic strategy for obesity and diabetes.
  • Targeting the βKlotho/FGFR1c complex with mimAb1 may offer a safer alternative to activating FGFR1c alone, avoiding potential side effects.

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

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

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...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood glucose levels...
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...