Mechanisms linking gut microbial metabolites to insulin resistance

Table 1 The effects of diet-derived gut bacterial metabolites on the pathogenesis of insulin resistance in various organs

Category	Metabolite	Target organ	Effects	Ref.
Carbohydrate
Fiber-derived	Acetate	Skeletal muscle	Increased lipid oxidation in vivo	Yamashita et al[75]
		Liver	Decreased lipogenesis in vivo	den Besten et al[47] and Yamashita et al[51]
			Increased lipid oxidation in vivo	den Besten et al[47], Yamashita et al[51], Kondo et al[52] and Sahuri-Arisoylu et al[53]
		Adipose tissue	Stimulated adipogenesis in vitro	Ge et al[60]
			Inhibited lipolysis in vitro and in vivo	Hong et al[59], Ge et al[60] and Jocken et al[61]
			Increased browning in vitro and in vivo	Sahuri-Arisoylu et al[53] and Hanatani et al[73]
		Whole body	Increased energy expenditure and fat oxidation in vivo and in humans	den Besten et al[47], Canfora et al[77] and van der Beek et al[78]
	Propionate	Liver	Suppressed gluconeogenesis in vitro	Yoshida et al[29]
			Decreased lipogenesis in vivo	den Besten et al[47]
			Increased lipid oxidation in vivo	den Besten et al[47]
		Adipose tissue	Increased adipogenesis in vitro	Ge et al[60]
			inhibit lipolysis in vitro and in vivo	Hong et al[59] and Ge et al[60]
			Improved inflammation in ex vivo	Al-Lahham et al[66]
		Intestine	Promoted gluconeogenesis in vivo	De Vadder et al[91]
		Whole body	Increased energy expenditure and fat oxidation in vivo and in humans	den Besten et al[47], Canfora et al[77] and Chambers et al[79]
	Butyrate	Skeletal muscle	Increased lipid oxidation in vitro and in vivo	Gao et al[48]
		Liver	Decreased lipogenesis in vivo	den Besten et al[47]
			Increased lipid oxidation in vivo	den Besten et al[47], Gao et al[48] and Mollica et al[49]
		Adipose tissue	decreased lipolysis in vitro	Ohira et al[67]
			Improved inflammation in vitro	Ohira et al[67]
			Increased thermogenesis in vivo	Gao et al[48] and Li et al[74]
		Intestine	Promoted gluconeogenesis in vitro and in vivo	De Vadder et al[91]
		Whole body	Increased energy expenditure and fat oxidation in vivo and in humans	den Besten et al[47], Gao et al[48] and Canfora et al[77]
	Succinate	Intestine	Promoted gluconeogenesis in vivo	De Vadder et al[92]
Protein
Protein-derived	Hydrogen sulfide	Liver	Increased gluconeogenesis in vitro	Zhang et al[32]
			Decreased glycogen synthesis in vitro	Zhang et al[32]
	Indole	Adipose tissue	Increased inflammation in vivo	Virtue et al[10]
	Indole-3-carboxylic acid	Adipose tissue	Increased inflammation in vivo	Virtue et al[10]
	Phenylacetic acid	Liver	Increased lipogenesis in ex vivo and in vivo	Hoyles et al[46]
Lipid and others
Linoleic acid-derived	10-oxo-12(Z)-octadecenoic acid	Adipose tissue	Induced adipogenesis in vitro	Goto et al[55]
			Increased thermogenesis in vivo	Kim et al[81]
	Conjugated linoleic acid	Adipose tissue	Increased energy expenditure	Takahashi et al[82], Park et al[83] and Lee et al[84]
Ferulic acid-derived	Ferulic acid 4-O-sulfate and Dihydroferulic acid 4-O-sulfate	Skeletal muscle	Increased glucose uptake in vitro	Houghton et al[19]
Resveratrol-derived	Trans-resveratrol 4’-O-glucuro-nide and Trans-resveratrol 3-O-sulfate	Skeletal muscle	Increased glucose uptake in vitro	Houghton et al[19]
Berries-derived	Isovanillic acid 3-O-sulfate	Skeletal muscle	Increased glucose uptake in vitro	Houghton et al[19]
Catecin-derived	4-hydroxy-5-(3,4,5-trihydroxyphenyl) valeric acid, 5-(3,4,5-trihydroxyphenyl)-γ-valerolac-tone, and 5-(3-hydroxyphenyl) valeric acid	Skeletal muscle	Increased glucose uptake in vitro	Takagaki et al[22]
Catecin-derived	5-(3,5-dihydroxyphenyl)-γ-valerolactone	Skeletal muscle	Increased glucose uptake in vitro and in vivo	Takagaki et al[22]
Bacteria-derived	Extracellular vesicles	Skeletal muscle	Decreased glucose uptake in vivo	Choi et al[20]
Choline-derived	Trimethylamine N-oxide	Liver	Increased gluconeogenesis in ex vivo and in vivo	Chen et al[33] and Gao et al[43]
		Adipose tissue	Promoted inflammation in vivo	Gao et al[43]