Angiotensin AT(2) receptor contributes towards gender bias in weight gain.
Obesity is a major disease condition, in turn leading to pathological changes collectively recognized as metabolic syndrome. Recently angiotensin receptor AT(2)R has been associated negatively with body weight (BW) gain in male mice. However, the gender differences in AT(2)R and BW changes have not been studied. To understand the gender based role of AT(2)R involving BW changes, we fed male and female wild type (WT) and AT(2)R knock out (AT(2)KO) mice with C57BL6 background with high fat diet (HFD) for 16 weeks. The male AT(2)KO had higher HFD calorie intake (WT: 1280±80; AT(2)KO:1680±80 kcal) but gained less BW compared with the WT (WT: 13; AT(2)KO: 6 g). Contrary to the male animals, the female AT(2)KO mice with equivalent caloric intake (WT: 1424±48; AT(2)KO:1456±80 kcal) gained significantly more BW than the WT mice (WT: 9 g; AT(2)KO: 15 g). The male AT(2)KO on HFD displayed lower plasma insulin level, less impaired glucose tolerance (GT), and higher plasma T3 compared with WT males on HFD; whereas the female AT(2)KO mice on HFD showed elevated levels of plasma insulin, more impaired GT, lower plasma T3 and higher free fatty acid and hepatic triglycerides compared with WT females on HFD. Interestingly, compared with WT, AT(2)KO female mice had significantly lower estrogen, which was further reduced by HFD. These results suggest that AT(2)R in female mice via potentially regulating estrogen may have protective role against BW gain and impaired glucose tolerance and lipid metabolism.
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
Preethi
P
Samuel
Mohammad Azhar
MA
Khan
Sourashish
S
Nag
Tadashi
T
Inagami
Tahir
T
Hussain
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D002149:Energy Intake; D004958:Estradiol / Q000652:urine; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005247:Feeding Behavior; D005260:Female; D005951:Glucose Tolerance Test; D006066:Gonads / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D012727:Sex Characteristics; D014280:Triglycerides / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood; D015430:Weight Gain
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D044139:Receptor, Angiotensin, Type 2; D014280:Triglycerides; D014284:Triiodothyronine; D004958:Estradiol