Table 2.

Metabolic and cardiac phenotypes of Raptor and Rictor knockout mice.

No.	Genes	Tissues	Models	Phenotypes	Ref.
	Adipose tissue
1	Raptor	Adipocyte Fabp4/aP2-Cre	HFD	Substantially less adipose tissue, protected against diet-induced obesity, hypercholesterolemia, and insulin resistance	[74]
2	Raptor	Adipocyte Adipoq-Cre	HFD	Progressive lipodystrophy with hepatic steatosis and insulin intolerance, resistant to diet-induced obesity, severe hepatomegaly	[75]
3	Raptor	Adipocyte Adipoq-Cre	HFD	Fails to completely suppress lipolysis in the fed state and displays prominent hypertriglyceridemia and hypercholesterolemia	[79]
4	Raptor	Adipocyte Adipoq-Cre	Cold, βAR agonist	Refractory to the β-adrenergic stimulation of UCP1 expression and expansion of beige/brite adipocytes in WAT	[41]
5	Raptor	Adipocyte Adipoq-Cre	Cold, HFD	Increased prostaglandin (PG) production by COX-2 and promotes differentiation of progenitor cells to beige adipocytes	[80]
6	Raptor	Global S791A knock-in	GLP-1R agonist	Partially resistant to GLP-1R agonist liraglutide-induced weight loss, lesser reduction in fat mass, lower energy expenditure	[62]
7	Rictor	Adipocyte Fabp4/aP2-Cre	HFD	Increased body (non-adipose organ) size, hyperinsulinemia but glucose-tolerant, elevated levels of IGF1	[81]
8	Rictor	Adipocyte Adipoq-Cre	HFD	Normal body growth, insulin intolerance, impaired adipose insulin signaling results in reduced glucose uptake and de novo lipogenesis	[82]
9	Rictor	Brown adipocyte Myf5-Cre	HFD	Decreased fat mass and adipocyte size, decreased lipogenesis but elevated mitochondrial activity in brown fat, protected against obesity and metabolic disease	[83]
10	Rictor	Brown adipocyte Ucp1-Cre	Cold, βAR agonist, HFD	Increased cold tolerance, inhibits de novo lipid synthesis, promotes lipid catabolism and thermogenesis, and protects against diet-induced obesity	[84]
	Liver
11	Raptor	Hepatocyte Albumin-Cre	Western diet	Gained less weight, reduced fasted liver size, suppresses hepatic de novo lipogenesis, protects mice from hepatic steatosis and hypercholesterolemia	[98]
12	Raptor	Hepatocyte AAV-TBG-Cre	Fasting and refeeding	Smaller liver with increased steatosis, higher hepatic TAG and decreased TAG secretion under fasting conditions	[113]
13	Raptor	Hepatocyte Albumin-Cre	HFD, hepatic carcinogen	Increased liver injuries, aberrant regeneration, enhanced fibrosis, inflammation, and hepatocarcinogenesis	[114]
14	Rictor	Hepatocyte Albumin-Cre	HFD	Smaller liver with lower glycogen and TG content, hepatic insulin resistance, dysregulated hepatic gluconeogenesis, glycolysis and de novo lipogenesis	[118]
15	Rictor	Hepatocyte Albumin-Cre	HFD	Failed to inhibit hepatic glucose output, glucose intolerance and insulin resistance, resistant to hepatic steatosis on a high-fat diet	[119]
	Heart
16	Raptor	Cardiomyocyte MHC-Cre	TAC	Acute cardiac dysfunction in response to overload, metabolic switch from fatty acid to glucose oxidation, abnormal mitochondria, increased apoptosis, and autophagy	[126]
17	Raptor	Cardiomyocyte MHC-Cre heterozygote	TAC	Attenuates heart failure induced by pressure overload or Gαq overexpression	[130]
18	Rictor	Cardiomyocyte MHC-Cre	TAC	Accelerates cardiac dysfunction after aortic constriction, reduces PKC protein levels, does not affect hypertrophy, fibrosis, or metabolic gene expression	[138]
19	Rictor	Cardiomyocyte AAV9 shRNA	MI	Increases myocardial damage and remodeling	[140]

Abbreviations: TBG: thyroxine binding globulin; TAC: transverse aortic constriction; MHC: α-myosin heavy chain; MI: myocardial infarction.