Table 1.

Roles of SESN2 in fatty liver diseases.

Disease type	Animal model	Intervention	Manifestations							Overall outcome	Reference
			Weight gain	Triglyceride level	Expression of lipogenic genes	Insulin resistance	Oxidative stress/ER stress/Inflammation/Apoptosis	Autophagy	Signaling
NAFLD	Mice fasted for 16 h and refed with a high-carbohydrate, fat-free diet for 16 h	SESN2 knockout	No data	No data	No data	No data	Increased oxidative stress and apoptosis	Decreased	SESN2/p62/Keap1/Nrf2	SESN2 deprivation aggravates liver damage inflicted by acute lipogenic stimulation.	[45]
	(1) Mice fed with a HFD for 4 months; (2) 4-month-old Lepob/ob mice fed with a LFD	SESN2 knockout	No data	Increased	Modestly increased	Increased	Enhanced ER stress, inflammation, and apoptosis	No data	SESN2/AMPK/mTORC1	SESN2 knockout mice exhibit obvious hepatosteatosis and liver damage with fibrosis tendency.	[60]
	Mice fed with a WD for 8 weeks	SESN2 knockout	Modestly increased	Increased	Increased	No data	Increased oxidative stress, ER stress, inflammation, and apoptosis	No data	SESN2/mTORC1/JNK	SESN12 knockout and SESN1/2/3 triple knockout mice are susceptible to WD-induced liver injury, hepatic steatosis, apoptosis, inflammation, and fibrosis.	[89]
	(1) Mice fed with a HFD for 3 months; (2) 4-month-old Lepob/ob mice fed with a LFD	SESN2 knockout	No differ from control	Increased	Modestly increased	Increased	No data	Decreased	SESN2/AMPK-TSC2/mTOR/AKT	SESN2 knockout mice display aggravated hepatosteatosis, glucose intolerance, and insulin resistance.	[90]
	Mice fed with a HFD for 2 months	Adenoviral expression of SESN2	No differ from control	No data	Decreased	Decreased	No data	No data	SESN2/GATOR2-mTORC2/AKT	Adenoviral expression of SESN2 decreases lipogenesis and gluconeogenesis.	[91]
	Mice fed with a HFD for 2 months	Resveratrol administration	No data	Decreased	Decreased	No data	No data	No data	SESN2/LXRα-RXRα-LXRE/SREBP-1c	SESN2 induction by resveratrol contributes to the inhibition of the LXRα activity and lipogenesis.	[92]
	Mice fed with a MCD diet for 3 weeks	Carbon monoxide administration	No data	Decreased	No data	No data	Decreased ER stress and inflammation	Increased	PERK-eIF2α-ATF4/SESN2/AMPK/mTORC1	Carbon monoxide-enhanced SESN2 expression diminishes lipid accumulation and liver damage through autophagy.	[95]
	Mice fed with a HFD for 2 months	Liraglutide administration	Decreased	Decreased	No data	Decreased	Decreased oxidative stress and inflammation	No data	SESN2/Nrf2/HO-1	SESN2 induced by liraglutide mitigates hepatic lipid accumulation, oxidative stress, and inflammation.	[97]
AFLD	Mice received alcohol gavage for 4 weeks	Pterostilbene administration	Increased	Decreased	No data	No data	Decreased inflammation	Increased	SESN2/p62/CCN1	Induction of SESN2 by pterostilbene promotes p62-mediated autophagic degradation of CCN1 and relieves hepatic damage.	[100]

AFLD alcoholic fatty liver disease, AKT protein kinase B, AMPK adenosine monophosphate-activated protein kinase, ATF4 activating transcription factor 4, CCN1 cellular communication network factor 1, eIF2α alpha subunit of eukaryotic translation initiation factor 2, ER endoplasmic reticulum, GATOR2 GTPase-activating protein activity towards Rags 2, HFD high-fat diet, HO-1 heme-oxygenase-1, JNK c-Jun N-terminal kinase, Keap1 Kelch-like ECH-associated protein 1, LFD low-fat diet, LXRα liver X receptor alpha, LXRE LXR response element, MCD methionine/choline deficiency, mTORC1 mechanistic target of rapamycin complex 1, NAFLD non-alcoholic fatty liver disease, Nrf2 nuclear factor E2-related factor 2, PERK protein kinase R-like endoplasmic reticulum kinase, RXRα retinoic acid receptor alpha, SESN2 Sestrin2, SREBP-1c sterol regulatory element-binding protein 1c, WD Western diet.