Essential roles of four-carbon backbone chemicals in the control of metabolism

Table 1 Summarizing table describing the biological and metabolic effects promoted by butyric acid and its analogues molecules

Molecule	Putative molecular target or mechanism involved	Overall biological response	Ref.
Butyric acid	Increased PGC1α expression and AMPK activity	Increased type I muscle fibers, increased insulin sensitivity, reduced adiposity	[14]
	Inhibition of HDACs	Decreased glycaemia in streptozotocin-induced diabetes. Decreased pancreatic β-cells apoptosis	[28]
	HDAC3 inhibition	Induction of FGF21, fatty acid oxidation and ketone bodies production	[33]
D-β-hydroxybutyrate	Binds and activates GPCR PUMA-G/Gpr109	Inhibition of adipocyte lipolysis	[63]
	Binds and activates GPCR FFA3/Grp41	Regulates energy consumption through FFA3/Grp41 activation in the sympathetic nervous system	[64]
	HDACs inhibition	Protection from oxidative stress	[65]
4-phenylbutyric acid	HDAC5 inhibition	Increased GLUT4 gene expression and promotion of glucose metabolism	[48]
	Inhibition of oxidative stress and endoplasmic reticulum stress	Alleviation of diabetic nephropathy in streptozotocin-induced diabetes	[40]
β-aminoisobutyric acid	Activates PPARα	Induction of hepatic β-oxidation and brown adipose tissue	[71]
	Restores normal plasma leptin levels	Increase of fatty acid oxidation and alleviation of diet-induced obesity in ob/+ heterozygous mice	[69]
	Induces liver ketogenesis, increasing circulating D-β-hydroxybutyrate	Decreased body fat mass	[68]

HDACs: Histone deacetylases; GPCR: G-protein coupled receptor; FGF-21: Fibroblast growth factor 21; FFA3/Grp41: Free fatty acids receptor 3; PPARα: Peroxisome proliferator-activated receptor alpha.