GDF15 deficiency promotes high fat diet-induced obesity in mice

Area of Science:

• Metabolic research
• Obesity research
• Endocrinology

Background:

• Pharmacological administration of Growth Differentiation Factor 15 (GDF15) reduces body weight in obese animal models.
• Circulating GDF15 levels are paradoxically elevated in obese individuals.
• The role of endogenous GDF15 in obesity pathogenesis remains unclear.

Purpose of the Study:

• To investigate the endogenous role of GDF15 in the development of diet-induced obesity.
• To determine the impact of GDF15 deficiency on metabolic parameters and associated conditions.

Main Methods:

• GDF15 knockout mice and wildtype controls were fed a high-fat diet to induce obesity.
• Assessment of body weight, glucose tolerance, locomotor activity, metabolic rate, and skin lesion incidence.
• Comparative analysis between GDF15 deficient and wildtype mice.

Main Results:

• GDF15 knockout mice exhibited increased susceptibility to diet-induced obesity compared to wildtype controls.
• Male GDF15 knockout mice displayed impaired glucose tolerance, reduced locomotor activity, and a lower metabolic rate.
• GDF15 deficiency exacerbated the development of diet-induced skin lesions.

Conclusions:

• Endogenous GDF15 plays a protective role in preventing obesity and associated metabolic dysfunctions.
• Lack of GDF15 worsens obesity progression and related pathological conditions.
• Elevated GDF15 in obesity may represent a compensatory mechanism against GDF15 resistance.