Literature summary for 2.8.2.4 extracted from

Garbacz, W.G.; Jiang, M.; Xu, M.; Yamauchi, J.; Dong, H.H.; Xie, W.
Sex- and tissue-specific role of estrogen sulfotransferase in energy homeostasis and insulin sensitivity (2017), Endocrinology, 158, 4093-4104 .

Search for more literature for 2.8.2.4

Cloned(Commentary)

Cloned (Comment)	Organism
gene EST, real-time PCR enzyme expression analysis	Mus musculus

Protein Variants

Protein Variants	Comment	Organism
additional information	mice with adipose tissue (WAT) reconstitution of Est in Est-deficient ob/ob mice (oae mice) are generated by crossing the obe mice with the aP2-Est transgenic mice that express Est in the adipose tissue under the control of the aP2 gene promoter. The resulting oae mice bear the expression of Est in the adipose tissue in the background of obe. Est-deficient ob/ob mice with transgenic reconstitution of Est in liver (ole mice) are generated by crossing the obe mice with the Lap-Est transgenic mice that express Est in the liver under the control of the liver-enriched activator protein (Lap) gene promoter. The resulting ole mice bear the expression of Est in the liver in the background of obe. Adipose reconstitution of Est improves the metabolic function of obe mice in a male-specific manner, phenotypes, overview. The reduced WAT local and systemic inflammation in oae males may have been accounted for by the upregulation of Lcn2. The induction of Lcn2 is consistent with the notion that the expression of Lcn2 can be suppressed by estrogens, so the increased deactivation of estrogen in oae mice causes a desuppression of Lcn2 in the adipose tissue. The induction of Lcn2 is bothWAT specific and male specific because the liver expression of Lcn2 is comparable between the obe and oae males, and the aP2-Est transgene has little effect on the adipose expression of Lcn2 in oae females. In contrast to the notion that Lcn2 might be an inflammatory marker, a striking negative association between the WAT expression of Lcn2 and TNF-alpha is found, suggesting that Lcn2 might actually antagonize TNF-alpha as part of a negative feedback loop. Treatment of differentiated 3T3-L1 cells with Lcn2 attenuates the TNF-alpha-responsive suppression of insulin signaling, including the expression of insulin-responsive genes such as Srbep-1c and Fas. Adipose reconstitution of Est fails to rescue the pancreatic beta cell damage in obe males	Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
3'-phosphoadenylyl sulfate + estrone	Mus musculus	-	adenosine 3',5'-bisphosphate + estrone 3-sulfate	-	?
3'-phosphoadenylyl sulfate + estrone	Mus musculus C57BL/6J	-	adenosine 3',5'-bisphosphate + estrone 3-sulfate	-	?

Organism

Organism	UniProt	Comment	Textmining
Mus musculus	P49891	-	-
Mus musculus C57BL/6J	P49891	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
3T3-L1 cell	-	Mus musculus	-
liver	liver has a low basal expression of Est, but the hepatic expression of Est is highly induced in the ob/ob, db/db, and HFD-induced obese mice	Mus musculus	-
additional information	the expression of Est exhibits both tissue and sex specificity. In male mice, the expression of Est is high in the white adipose tissue (WAT) and testis	Mus musculus	-
testis	high level in male mice	Mus musculus	-
white adipose tissue	WAT, high level in male mice	Mus musculus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
3'-phosphoadenylyl sulfate + estrone	-	Mus musculus	adenosine 3',5'-bisphosphate + estrone 3-sulfate	-	?
3'-phosphoadenylyl sulfate + estrone	-	Mus musculus C57BL/6J	adenosine 3',5'-bisphosphate + estrone 3-sulfate	-	?

Synonyms

Synonyms	Comment	Organism
EST	-	Mus musculus
estrogen sulfotransferase	-	Mus musculus
SULT1E1	-	Mus musculus

Expression

Organism	Comment	Expression
Mus musculus	liver has a low basal expression of Est, but the hepatic expression of Est is highly induced in the ob/ob, db/db, and HFD-induced obese mice	up

General Information

General Information	Comment	Organism
malfunction	loss of Est in male ob/ob mice, but not in female ob/ob mice, exacerbates the diabetic phenotype. Transgenic reconstitution of Est in the adipose tissue, but not in the liver, attenuates diabetic phenotype in Est-deficient ob/ob mice (obe mice). Mechanistically, adipose reconstitution of Est in obe mice (oae mice) results in reduced local and systemic inflammation, improved insulin sensitivity, and increased energy expenditure. At the molecular level, adipose induction of lipocalin-2 (Lcn2) in oae males may have contributed to the inhibition of inflammation because the level of Lcn2 is negatively associated with tumor necrosis factor (TNF) alpha expression, and treatment of differentiated adipocytes with Lcn2 antagonizes TNFalpha-responsive inhibition of insulin signaling. The metabolic benefit of adipose reconstitution of Est is sex specific, because adipose reconstitution of Est in obe females has little effect. Interestingly, despite their improved metabolic functions, obe male mice with reconstituted Est in their adipose tissue fail to ameliorate the impairment of the structure and function of the pancreatic islets	Mus musculus
physiological function	Estrogen sulfotransferase catalyzes the sulfoconjugation and deactivation of estrogens. plays an important role in regulating the tissue and systemic estrogen activity. Sulfoconjugation inactivates estrogens because the sulfonated estrogens cannot bind to the estrogen receptors and they are more susceptible to urinary excretion. Sex- and tissue-specific role of estrogen sulfotransferase in energy homeostasis and insulin sensitivity. The WATexpression of Est ensures a sufficient deactivation of estrogens in males, whereas the testicular expression of Est protects the male reproductive system from estrogen toxicity. The Est expression in the adipose tissue, but not in the liver, is essential to protect mice from systemic and local inflammation and metabolic syndrome in a male-specific manner. Adipose reconstitution of Est fails to rescue the pancreatic beta cell damage in Est-deficient ob/ob (obe) male mice. Liver reconstitution of Est fails to ameliorate inflammation and diabetic phenotype in obe male mice	Mus musculus

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Release 2023.1 (January 2023)