Table 2 Main Performance, hypoglycemic mechanism and glucose outcome of FXR and TGR5 knockout models

FXR–/–

C57BL/6 J

Mice

body

GW4064

GW4064 do not raise blood glucose, while 8-CPT-cAMP (PKA activator) raise blood glucose

In the presence of glucagon, GW4064 promote gluconeogenesis through the CCG-PKA signaling pathway by promoting Fbp1, Pck1, and G6pc expression

In the presence of cAMP analogs, it inhibits gluconeogenesis through the SHP / Nr0b2 signaling pathway

Raise [94]

FXR–/–

C57BL/6JMice

body

VSG

Body weight and blood glucose are not improved after VSG

Reduce expression of FXR transcriptional target genes

2. no change in intestinal Bacteroides

3. BA in the liver remained unchanged, while CA, TCA and GCA in the intestine decreased

4.TCA supplementation reverses the metabolic benefits of VSG

Unchange [96]

FXR–/–

Not mentioned

body

–

Raise blood glucose and blood lipids

Aggravate diabetic cardiomyopathy, diabetic myocardial fibrosis

Increase expression of lipid synthesis and lipid transport genes in diabetic cardiomyocytes (SCD-1, SREBP-1c, FAS, ACC, LOX-1, LDLR)

Raise [108]

FXR–/–

Not mentioned

body

BD

FXR-/- mice are resistant to HFD-induced obesity

1.BD significantly increase the expression of PGC-1ß in the liver of WT mice, but BD faile to promote FXR-/- mice

2.Increase in Proteobacteria, decrease in Bacteroides

Rasie [109]

FXR–/–

C57BL/6 J mice

body

RYGB

FXR-/- mice slow weight gain and improve glucose homeostasis

The GLP-1 antagonist Ex-9 attenuate the postoperative hypoglycemic effect of RYGB in the control group but do not alter the FXR-/-group, suggesting an association with the FXR-GLP-1 axis

Reduce [110]

FXR–/–

C57BL/6 mice

intestine

GB-IL

No change in weight after GB-IL, no improvement in glucose tolerance

Failure of BAs to activate FXR pathway and unaltered GLP-1 levels

Unchange [88]

FXR–/–

Not mentioned

intestine

GS3972

1. ileal expression of Fgf15 was significantly reduced, Cyp7a1 expression was significantly higher in the liver, and Cyp8b1 was not affected

2. Long-term HFD resulted in impaired glucose metabolism and reduced insulin sensitivity in WT mice and FXR-/- mice

1.Liver: GS3972 treatment significantly increase the expression of FXR target genes SHP in WT and FXR-KO mice, while Cyp7a1 and Cyp8b1 expression is significantly decreased

2.Ileum: Fgf15 and ileal bile acid binding protein (I-BABP) are expressed in the ileum of WT mice after GS3972 treatment, but not in FXR-KO mice

Unchange [95]

FXR–/–

C57BL/6 J

Mice

intestine

VSG

Reduce body weight and improve insulin sensitivity

intestine:decreased levels of taurine-conjugated BAs

2.Increase in Firmicutes and Lactobacillus

Reduce [96]

FXR–/–

C57BL/6 J

Mice

Liver

VSG

Reduce body weight and improve insulin sensitivity

1.intestine:decreased levels of taurine-conjugated BAsBAs

2.Increase in Firmicutes and Lactobacillus

Reduce [96]

FXR–/–

C57BL/6 J

Mice

Adipocyte

–

Do not improve HFD-induced obesity but improve insulin sensitivity

Promote AKT phosphorylation, promote GSTA4 expression and reduce oxidative stress

Reduce [111]

TGR5–/–

C57BL/6 J

Mice

body

VSG

Decrease in body weight, no change in energy expenditure, no change in plasma insulin concentration

Cyp8b1 expression is inhibited and the ratio of 12α-OH:non-12α-OH BAs is increased

Unchange [112]

TGR5–/–

C57BL/6 J

Mice

body

HDCA

1. insulin secretion is higher and there is no effect on blood glucose

2. ω-MCA and HDCA levels in the portal vein are increased only in the WT mice. group, but not in the TGR5- KO mice group,

HDCA promotes insulin secretion and regulates blood glucose by activating the TGR5-GLP-1 signaling pathway

Unchange [113]

TGR5–/–

C57BL/6 Mice

body

GB-IL

GB-IL postoperative weight loss and improved glucose tolerance

Associated with activation of FXR by BAs and promotion of GLP-1 secretion

Reduce [88]

TGR5 overexpression

C57BL/6 mice

skeletal muscle

TLCA

Levels of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P) are significantly reduced in Tg mice

Promote glycolysis, do not improve muscle insulin sensitivity, do not improve insulin resistance

Unchange [105]