Table 1.
Summary of studies on GPCR-mediated actions of ketone bodies.
| Reference | Animal or cell model | Ketone body (concentration) | GPCR involved | Effects |
|---|---|---|---|---|
| Zhang SJ 2021(50) | BMDMs from wt mice | β-OHB (10 mM) | GPR109A | ↓ M1 polarization ↑ Promoting cholesterol efflux in macrophages |
| Lee AK 2020 (51) | Aged rats | β-OHB (10 and 100 mg/kg/day) | GPR109A | ↑ AMPK levels ↓ Hepatic ER stress and lipid accumulation |
| HepG2 cells | β-OHB (200 and 400 µM) | |||
| Rahman M 2014 (45) | KD-fed mice (wt and GPR109A-/-) | β-OHB | GPR109A | ↑ COX1-mediated neuroprotective phenotype of monocytes and/or macrophages |
| Fu SP 2015 (52) | Primary rat microglial cells | β-OHB (1.5 mM) | GPR109A | ↓ LPS-induced NF-κB activation and IL-1β, IL-6 and TNF-α production |
| Chen Y 2018 (53) | C57BL/6 mice | β-OHB (3 mmol/kg) | GPR109A | ↑ M2 phenotype of intrahepatic macrophages |
| Won YJ 2013 (54) | Superior cervical sympathetic ganglionic neurons | β-OHB (10 mM) | GPR41 | ↓ Ca2+ channel currents |
| Kimura I 2011 (55) | HEK293 expressing mouse GPR41 and sympathetic neurons | β-OHB (0.1 and 1 mM) | GPR41 | ↓ propionate-induced ERK1/2 activation ↓ activity in sympathetic neurons |
| Miyamoto J 2019 (56) | GPR43-overexpressing HEK293 | Acetoacetate (0.3 mM) | GPR43 | ↓ cAMP levels induced by forskolin |
| Gpr43−/− mice | Acetoacetate (500 mg/kg) | ↑ lipolysis by activating plasma LPL activity |
BMDM, bone marrow-derived macrophages; β-OHB, β-hydroxybutyrate; AMPK, AMP-activated protein kinase; COX1, cyclooxygenase 1;ERK1/2, Extracellular signal-regulated protein kinase; LPS, lipopolysaccharide; NF-κB, nuclear factor k B.
↓, decrease; ↑ increase.