Abstract
Acetate is an endogenous metabolite of fatty acid β-oxidation produced in the liver mitochondria under conditions of starvation. Orally administered acetate is immediately taken up from the intestine and excreted into the bloodstream. The acetate is then absorbed by tissues and activates AMP-activated protein kinase (AMPK) by increasing the AMP/ATP ratio. AMPK acts as the key metabolic master switch, and regulates a number of enzymes involved in lipid homeostasis. Treatment with acetate results in a marked reduction of lipid accumulation in adipose tissue, protection against accumulation of fat in the liver, and improves glucose tolerance. It decreases the transcripts of lipogenic genes in the liver, indicating inhibition of lipogenesis in that organ. Furthermore, acetate treatment results in a higher rate of oxygen consumption and a smaller size of lipid droplets in white and brown adipose tissues. These results indicate that acetate is formed endogenously under conditions of starvation and utilized as a biological fuel, wheras acetate taken up under fed conditions has potential to prevent obesity and obesity-linked type 2 diabetes.
