Inhibitors of mammalian acetyl-CoA carboxylase

Area of Science:

• Biochemistry
• Pharmacology
• Metabolic Diseases

Background:

• Acetyl-CoA carboxylase (ACC) regulates fatty acid synthesis and oxidation.
• Dysregulation of ACC is linked to cardiometabolic risk factors like obesity and diabetes.
• Targeting ACC offers a potential therapeutic strategy for metabolic syndrome.

Purpose of the Study:

• To explore the therapeutic potential of inhibiting acetyl-CoA carboxylase (ACC) for cardiometabolic risk factors.
• To review the current landscape of ACC inhibitors and their therapeutic implications.
• To assess the potential of isozyme-selective vs. nonselective ACC inhibition.

Main Methods:

• Review of scientific and patent literature on ACC inhibitors.
• Analysis of studies involving ACC2 knockout mice and animal models.
• Examination of co-crystallization data of ACC domains with substrates and inhibitors.

Main Results:

• ACC inhibition favorably affects cardiometabolic risk factors by inhibiting fatty acid synthesis and stimulating oxidation.
• Studies in animal models demonstrate the potential of ACC inhibition for metabolic syndrome treatment.
• Diverse classes of ACC inhibitors have been identified, with varying mechanisms.

Conclusions:

• ACC inhibition is a promising therapeutic strategy for metabolic syndrome, obesity, and diabetes.
• Isozyme-nonselective ACC inhibitors may offer optimal therapeutic benefits.
• Further research is needed to fully elucidate the advantages and liabilities of isozyme-selective inhibitors.