Pregnancy in Obese Mice Protects Selectively against Visceral Adiposity and Is Associated with Increased Adipocyte Estrogen SignallingReportar como inadecuado

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Maternal obesity is linked with increased adverse pregnancy outcomes for both mother and child. The metabolic impact of excessive fat within the context of pregnancy is not fully understood. We used a mouse model of high fat HF feeding to induce maternal obesity to identify adipose tissue-mediated mechanisms driving metabolic dysfunction in pregnant and non-pregnant obese mice. As expected, chronic HF-feeding for 12 weeks preceding pregnancy increased peripheral subcutaneous and visceral mesenteric fat mass. However, unexpectedly at late gestation E18.5 HF-fed mice exhibited a remarkable normalization of visceral but not peripheral adiposity, with a 53% reduction in non-pregnant visceral fat mass expressed as a proportion of body weight P<0.001. In contrast, in control animals, pregnancy had no effect on visceral fat mass proportion. Obesity exaggerated glucose intolerance at mid-pregnancy E14.5. However by E18.5, there were no differences, in glucose tolerance between obese and control mice. Transcriptomic analysis of visceral fat from HF-fed dams at E18.5 revealed reduced expression of genes involved in de novo lipogenesis diacylglycerol O-acyltransferase 2 - Dgat2 and inflammation chemokine C-C motif ligand 2 - Ccl2 and upregulation of estrogen receptor α ERα compared to HF non pregnant. Attenuation of adipose inflammation was functionally confirmed by a 45% reduction of CD11b+CD11c+ adipose tissue macrophages expressed as a proportion of all stromal vascular fraction cells in HF pregnant compared to HF non pregnant animals P<0.001. An ERα selective agonist suppressed both de novo lipogenesis and expression of lipogenic genes in adipocytes in vitro. These data show that, in a HF model of maternal obesity, late gestation is associated with amelioration of visceral fat hypertrophy, inflammation and glucose intolerance, and suggest that these effects are mediated in part by elevated visceral adipocyte ERα signaling.

Autor: Silvia M. A. Pedroni, Sophie Turban, Tiina Kipari, Donald R. Dunbar, Kerry McInnes, Philippa T. K. Saunders, Nicholas M. Morton,



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