Table 1.

The role of short-chain fatty acids in different disorders.

Disease	SCFA	Model	Function	Ref.
Inflammatory bowel disease	Acetate	Gpr43−/−, Gpr109a−/−, Nlrp3−/− and Nlrp6−/− mice	Induces NLRP3 inflammosome activation to maintain tissue homeostasis	[133]
	Butyrate	Niacr1+/− Apc min/+ and Niacr1−/− Apc min/+ mice	Increases colonic DCs and macrophages’ production of IL-10, inducing Treg generation	[127]
		Foxp3 ΔCNS1, Foxp3 GFP, Foxp3 Thy1.1 and Gpr109a−/− mice	Promotes Treg differentiation through enhancing Foxp3 activity	[128]
		GPR109a−/− and WT mice	Inhibits AKT and NF-κB p65 signaling pathways in macrophages	[131]
		BMDM cells, C57BL/6 and CX3CR1-GFP/+ mice	Reduces NO, IL-6 and IL-12p40 secretion by macrophages	[132]
		GPR43−/−, Prdm1−/− and WT mice	Increases AREG expression levels in DCs to promote tissue repair	[134]
		Cdx2-IEC monolayer	Induces production of claudin-1 to enhance barrier functions	[138]
	Propionate	Gpr43−/− and Gpr43+/+ mice	Promotes Treg differentiation through GPR-43	[129]
	All SCFAs	HeLa and HEK293 cell lines	Inhibit NF-κB activity through GPR43—βarrestin interactions	[130]
		Isolated human neutrophils, monocytes and PBMC	Promotes anti-inflammatory effects via the regulation of PGE2, cytokine and chemokine release	[58]
		CD4+ T cells and ILCs	Induces production of IL-22 to promote barrier functions	[135]
Colorectal cancer	Butyrate	Caco-2 cell line	Enhances cancer cells’ apoptosis by alterations in the redox state and D-glucose metabolism	[140]
		MCF-7 (T5) and MDA MB 231 cell lines	Arrests cancer cells’ proliferation through upregulation of p21	[141]
	Propionate	Caco-2, HCT116, HCT8, HT-29, SW620, SW480, CBS, FET and MOSER cell lines	Arrests cancer cells’ proliferation through p21 upregulation and decrease in cyclin D3, CDK-1 and CDK-2	[142]
Hypertension	Acetate and propionate	Olfr78−/− and Gpr41−/− mice	Increase blood pressure through Olfr-78	[144]
		Gpr41−/− and WT mice	Reduces blood pressure by binding GRP-41	[145]
	Butyrate	Vagotomized Sheffield strain male Wistar rats	Reduces blood pressure through the regulation of afferent vagal terminals	[146]
Atherosclerosis	Butyrate	ApoE −/− mice	Reduces CCL-2, VCAM-1, and MMP-2 production to stabilize atherosclerotic plaques	[148]
Obesity	Acetate	C57BL/6 male mice	Decreases appetite through central hypothalamic mechanisms	[43]
	Propionate	Isolated human colonic cells	Reduces food intake through the secretion of PPY and GLP-1 via GPR-41	[153]
	Propionate and butyrate	NCI-h716 and HuTu-80 cells	Reduce food intake through the secretion of PPY via inhibition of HDACs	[154]
Metabolic syndrome	Acetate	Isolated adipocytes from GPR43 knockout mice	Decreases lipid plasma levels through inhibition of lipolysis via GPR-43	[159]
	Propionate	Human subjects and in vitro isolated human islets	Enhances glucose-stimulated insulin release and increases β-cell mass	[155]
		Human adipose tissue culture	Decreases lipid plasma levels by stimulating lipogenesis	[160]
	Propionate and butyrate	Stromal vascular fraction of the porcine subcutaneous fat	Stimulates adipocyte differentiation	[156]
	All SCFAs	PPARγ f/f and PPARγ lox/lox mice	Regulate gluconeogenesis and lipogenesis through PPARγ downregulation	[46]
		Male Golden hamsters	Decrease cholesterol plasma levels by enhancing its hepatic uptake	[161]