Atf3 induction is a therapeutic target for obesity and metabolic diseases

Area of Science:

• Metabolic research
• Obesity research
• Molecular biology

Background:

• Activating transcription factor 3 (Atf3) is implicated in obesity and metabolism, but its precise role in mice is debated.
• Understanding Atf3's function is crucial for developing novel therapeutic strategies for metabolic disorders.

Purpose of the Study:

• To investigate the role of Atf3 in mouse models of obesity and metabolic dysfunction.
• To explore Atf3 expression as a potential therapeutic target for obesity and related metabolic diseases.

Main Methods:

• Utilized Atf3 knockout (KO) mice and wild-type (WT) littermate controls.
• Administered high-fat diet (HFD) and chow diet (CD) to assess metabolic phenotypes.
• Investigated the effect of sulfuretin, an Atf3 inducer, and identified other small molecule Atf3 inducers.

Main Results:

• Atf3 KO mice exhibited aggravated weight gain and impaired glucose metabolism on HFD compared to WT mice.
• Aged Atf3 KO mice on CD showed increased body weight and fat mass.
• The anti-obese effects of sulfuretin were abolished in Atf3 KO mice, highlighting Atf3's necessity.

Conclusions:

• Atf3 plays a significant role in regulating body weight and glucose homeostasis in mice.
• Targeting Atf3 induction, potentially through small molecule inducers, represents a promising therapeutic avenue for preventing and treating obesity and metabolic diseases.