Estradiol regulates insulin signaling and inflammation in adipose tissue.
BACKGROUND
Obesity-associated low-grade inflammation at white adipose tissue (WAT) leads to metabolic defects. Sex steroid hormone estrogen may be protective against high-fat diet (HFD)-induced obesity and insulin resistance. This has been tested by many previous studies utilizing rodent models of ovariectomy (OVX) and/or treatment of estradiol (E2), the major biologically active form of estrogen. Body weight and adiposity are increased by OVX and reduced following E2 treatment, however. Thus, the protective roles of E2 may be secondary effects to the changes in body weight and adiposity. We hypothesize that E2 directly prevents inflammation and maintains insulin sensitivity in WAT independent of energy status using mice with similar body weights and adiposity.


METHODS
Four groups of female C57BL/6 mice were used, including sham-operated mice treated with vehicle for E2 and fed with either a low-fat diet (LFD; Sham-Veh-LFD) or a HFD (Sham-Veh-HFD), and HFD-fed OVX mice treated with either vehicle (OVX-Veh-HFD) or E2 (OVX-E2-HFD). Body weight and abdominal parametrial WAT mass, insulin signaling, and expression levels of genes related to low-grade inflammation in WAT were compared between these groups pair-fed with equal amounts of calories for a period of 4 days.


RESULTS
Body weights and WAT mass were similar in all four groups. OVX-Veh-HFD mice had impaired insulin signaling associated with rapid activation of inflammation, whereas OVX-E2-HFD group maintained insulin sensitivity without showing inflammation in WAT.


CONCLUSIONS
E2 directly contributed to the maintenance of insulin sensitivity during the early phase of development of metabolic dysfunction, possibly via preventing low-grade inflammation in WAT.
Minqian
M
Shen
Shiva P D Senthil
SP
Kumar
Haifei
H
Shi
D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D004435:Eating; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
D004967:Estrogens; D007328:Insulin; D004958:Estradiol