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An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice

William L Holland1, Andrew C Adams, Joseph T Brozinick

  • 1Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA.

Cell Metabolism
|May 14, 2013
PubMed

Insights

Fibroblast growth factor 21 (FGF21) regulates metabolism by stimulating adiponectin secretion. This action is crucial for FGF21 to improve energy expenditure, lower ceramide levels, and enhance insulin sensitivity in obese mice.

Area of Science:

  • Metabolic regulation
  • Endocrinology
  • Lipid metabolism

Background:

  • Fibroblast growth factor 21 (FGF21) is a key metabolic regulator.
  • Insulin resistance is linked to intracellular lipid accumulation and ceramide buildup.
  • The precise mechanisms of FGF21 action remain unclear.

Purpose of the Study:

  • To investigate the role of adiponectin in mediating FGF21's metabolic effects.
  • To determine if adiponectin is essential for FGF21 to improve insulin sensitivity and energy expenditure.

Main Methods:

  • Administered FGF21 to wild-type and adiponectin-knockout mice.
  • Assessed changes in adiponectin secretion, energy expenditure, ceramide levels, and blood glucose.
  • Utilized diabetic Lep(ob/ob) and diet-induced obese (DIO) mouse models.

Main Results:

  • FGF21 significantly increased adiponectin secretion and reduced ceramide accumulation in obese rodents.
  • Adiponectin-knockout mice did not exhibit FGF21-induced improvements in energy expenditure or ceramide reduction.
  • FGF21's glucose-lowering and insulin-sensitizing effects were dependent on the presence of functional adiponectin.

Conclusions:

  • FGF21 is a potent stimulator of adiponectin secretion.
  • Adiponectin is critical for FGF21 to exert its beneficial effects on glycemic control and insulin sensitivity.

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