Table 3.

Paradoxical role of sortilin in lipoprotein metabolism

Model system	Diet	Sex	Method	TC/LDL-C	apoB secretion	LDL uptake	Reference
Upregulation of Sort1
HEK293 cells	NA	NA	Plasmid	NA	ND	↑	Linsel-Nitschke et al. (37)
HeLa T-Rex cells	NA	NA	Plasmid	NA	ND	↑	Tveten et al. (176)
HuH7 cells	NA	NA	LV	NA	↓	↑	Strong et al. (9)
McA cells	NA	NA	Plasmid	NA	—	ND	Conlon et al. (170)
hAPOB McA cells	NA	NA	Plasmid	NA	↓	ND	Amengual et al. (116)
hAPOB McA cells	NA	NA	Plasmid	NA	↓	ND	Conlon et al. (170)
HepG2 cells	NA	NA	AV	NA	↓	ND	Bi et al. (39)
WT mouse heps	CD	♂	AV	NA	↓	ND	Bi et al. (39)
Apobec−/−;APOB Tg mouse heps	CD	NR	AAV8-TBG	NA	↓	ND	Musunuru et al. (19)
Apobec−/−;APOB Tg;Ldlr+/− mouse heps	CD	♀	AAV8-TBG	NA	↓	ND	Strong et al. (9)
Apobec−/−;APOB Tg;Ldlr+/− mouse heps	CD	NR	AAV8-TBG	NA	↓	ND	Musunuru et al. (19)
WT mice	CD	♀	AAV8-TBG	ND	↓	↑	Strong et al. (9)
WT mice	CD	♂	AAV8-TBG	↓	—	ND	Conlon et al. (170)
WT mice	CD	♂	AV	↓	ND	ND	Bi et al. (39)
WT mice	CD	NR	AAV8	ND	—	ND	Ai et al. (40)
WT mice	WD	NR	AV	↑	ND	ND	Kjolby et al. (20)
WT mice	HFD	♂	AAV8-TBG	↓	↓	ND	Conlon et al. (170)
WT mice	HFD	NR	AAV8	ND	↓	ND	Ai et al. (40)
Apobec−/−;APOB Tg mice	CD	NR	AAV8-TBG	↓	↓	ND	Musunuru et al. (19)
Apobec−/−;Ldlr−/− mice	CD	NR	AAV8-TBG	↓	ND	ND	Musunuru et al. (19)
Apobec−/−;APOB Tg;Ldlr−/−mice	CD	NR	AAV8-TBG	↓	ND	ND	Musunuru et al. (19)
Apobec−/−;APOB Tg;Ldlr+/− mice	CD	NR	AAV8-TBG	↓	ND	ND	Musunuru et al. (19)
Ldlr−/− mice	CD	♀	AAV8-TBG	ND	↓	↑	Strong et al. (9)
Ldlr−/− mice	WD	♂	LV	↑	ND	ND	Lv et al. (12)
Ldlr−/− mice	WD	NR	AV	↑	ND	ND	Kjolby et al. (20)
ob/ob mice	CD	♂	AV	↓	ND	ND	Bi et al. (39)
ob/ob mice	WD	NR	AAV8	ND	↓	ND	Ai et al. (40)
Downregulation of Sort1
HeLa T-Rex cells	NA	NA	siRNA	NA	ND	↓	Tveten et al. (176)
HepG2 cells	NA	NA	siRNA	NA	ND	↓	Lu et al. (159)
HepG2 cells	NA	NA	siRNA	NA	—	ND	Conlon et al. (170)
HepG2 cells + FA	NA	NA	siRNA	NA	↑	ND	Conlon et al. (170)
A431 cells	NA	NA	siRNA	NA	ND	↓	Lu et al. (159)
HUES 1 and 9 HLCs	NA	NA	TALEN KO	NA	↑	ND	Ding et al. (177)
McA cells	NA	NA	shRNA	NA	—	ND	Sparks et al. (115)
McA cells	NA	NA	siRNA	NA	—	ND	Conlon et al. (170)
McA cells - serum-starved	NA	NA	shRNA	NA	↑	ND	Sparks et al. (115)
McA cells + FA, Cer, or Tun	NA	NA	siRNA	NA	↑	ND	Conlon et al. (170)
hAPOB McA cells	NA	NA	siRNA	NA	↑	ND	Conlon et al. (170)
Sort1−/− mouse heps	WD	NR	Global KO	NA	↓	—	Kjolby et al. (20)
Sort1−/− mouse heps	CD	♂	Global KO	NA	—	ND	Conlon et al. (170)
Sort1−/− mouse heps + FA	CD	♂	Global KO	NA	↑	ND	Conlon et al. (170)
Apobec−/−;APOB Tg;Ldlr+/− mouse heps	CD	NR	siRNA	NA	↑	ND	Musunuru et al. (19)
Sort1−/− mice	CD	♀	Global KO	ND	ND	↓	Strong et al. (9)
Sort1−/− mice	CD	♂	Global KO	—	ND	ND	Goettsch et al. (90)
Sort1−/− mice	CD	♂	Global KO	—	—	ND	Conlon et al. (170)
Sort1−/− mice	CD	NR	Global KO	↑	ND	ND	Musunuru et al. (19)
Sort1−/− mice	CD	NR	Global KO	—	ND	ND	Butkinaree et al. (136)
Sort1−/− mice	CD	♂	Hep KO	—	ND	ND	Chen et al. (55)
Sort1−/− mice	CD	♂	Hep KO	—	—	ND	Conlon et al. (170)
Sort1−/− mice	WD	NR	Global KO	↓	↓	ND	Kjolby et al. (20)
Sort1−/− mice	WD	♂	Hep KO	↓	ND	ND	Chen et al. (55)
Sort1−/− mice	HFD	♂	Global KO	↓	ND	ND	Rabinowich et al. (184)
Sort1−/− mice	HFD	♂	Global KO	↑	↑	ND	Conlon et al. (170)
Sort1−/− mice + Tun	CD	♂	Global KO	ND	↑	ND	Conlon et al. (170)
Apobec−/−;APOB Tg;Sort1−/− mice	CD	♀	Global KO	—	↓	ND	Strong et al. (9)
Apobec−/−;APOB Tg;Sort1−/− mice	WD	♂	Global KO	—	ND	ND	Patel et al. (32)
Apobec−/−;APOB Tg mice	CD	NR	siRNA	↑	ND	ND	Musunuru et al. (19)
Apobec−/−; APOB Tg; Ldlr−/− mice	CD	NR	siRNA	↑	ND	ND	Musunuru et al. (19)
Apobec−/−;APOB Tg;Ldlr+/− mice	CD	NR	siRNA	↑	ND	ND	Musunuru et al. (19)
Ldlr−/−;Sort1−/− mice	CD	♀	Global KO	↓	ND	—	Strong et al. (9)
Ldlr−/−;Sort1−/− mice	CD	♀	Global KO	—	ND	ND	Hagita et al. (178)
Ldlr−/−;Sort1−/− mice	WD	NR	Global KO	↓	ND	ND	Kjolby et al. (20)
Ldlr−/−;Sort1−/− mice	HF/HC	♀	Global KO	↓	ND	ND	Hagita et al. (178)
Ldlr−/−;Sort1−/− mice	HF/HC	♀	Global KO	—	ND	ND	Goettsch et al. (90)
Ldlr−/−;Sort1−/− mice	HF/HC	♂	Global KO	—	ND	ND	Goettsch et al. (90)
Apoe−/−;Sort1−/− mice	WD	♀	Global KO	—	ND	ND	Mortensen et al. (33)
Apoe−/−;Sort1−/− mice	WD	♂	Global KO	—	ND	ND	Mortensen et al. (33)
L1B6Ldlr−/−; Sort1−/− mice	WD	♂	siRNA	ND	↑	ND	Ai et al. (40)
ob/ob mice + PBA	CD	NR	siRNA	ND	↑	ND	Ai et al. (40)

AAV8-TBG; adeno-associated virus 8 with thyroxine-binding globulin promoter; AV, adenovirus; Cer, ceramide; heps, primary hepatocytes; HLC, hepatocyte-like cell; HUES, human embryonic stem cell line; LV, lentivirus; NA, not applicable; ND, not determined; NR, not reported; PBA, 4-phenyl butyric acid; Tun, tunicamycin; —, no difference.

Summary of published results on the effect of Sort1 manipulation on lipoprotein metabolism.