Table 1 Genes of interest and their functions

GPR40

M/LCFA receptor expressed in pancreatic α- and β-cells, enteroendocrine cells, immune cells, taste buds, and the central nervous system. Stimulation invokes intracellular calcium response and ERK signaling, or increases in cAMP. Mediates insulin release from β-cells, glucagon release from α-cells, and incretins in the gastrointestinal tract in response to free fatty acid (FFA) ligands, playing a central role in glucose homeostasis. Promotes activation and superoxide production in bovine neutrophils. May regulate secretion of brain-derived neurotrophic factor in neuroblastoma cells.

[8, 11, 38, 48, 66]

GPR120

M/LCFA receptor expressed in adipocytes and adipose tissue, macrophages, enteroendocrine cells, pancreatic α-cells, taste buds, and lungs. Stimulation invokes intracellular calcium response and ERK signaling. Stimulation with ω-3 FA leads to β-arrestin2-mediated inhibition of TAK1 (i.e.: anti-inflammatory signaling). Promotes glucose uptake via GLUT4 and G-protein-related insulin stimulatory effects in adipocytes. Promotes incretin (e.g., GLP-1) release in gastrointestinal tract, and glucagon release in α-cells. Reduces inflammatory gene expression in macrophages and adipose, as well as macrophage invasion into adipose tissue.

[38, 44, 49, 67, 68]

GPR84

MCFA receptor expressed in adipocytes and immune cells, including leukocytes. Expression is upregulated in macrophages by LPS. Promotes pro-inflammatory cytokine and chemokine signals.

[38, 69, 70]

HCAR2/3

Nicotinic acid and butyrate/β-hydroxybutyrate receptor expressed in adipose tissue, immune cells, spleen, colon, pancreatic β-cells, and mammary epithelium. Expression is upregulated in adipose and macrophages by LPS and other pro-inflammatory factors. Activation by niacin or BHBA decreases cAMP levels in adipose tissue, thereby reducing lipolysis, plasma FFA, and availability for triglyceride synthesis. Decreases in cAMP also occur in β-cells, inhibiting insulin release. Promotes release of prostaglandins from immune cells, including macrophages. Invokes apoptotic pathways in neutrophils and some cancer cells (e.g., breast and colon cancer).

[12, 46, 71–73]