Perinatal Lack of Maternal IL-6 Promotes Increased Adiposity During Adulthood in Mice

Abstract

The perinatal environment appears important in establishing metabolic phenotypes in adulthood. Mice deficient in IL-6 (IL-6(-/-)) tend to develop mature-onset obesity, but it is unknown whether perinatal exposure to IL-6 produced by the dam influences the metabolism of adult offspring. To address this issue, we monitored IL-6(-/-) offspring of IL-6(-/-) or IL-6(+/-) dams, as well as wild-type (WT) mice. At adult age, IL-6(-/-) mice weighed significantly more and had more body fat than WT mice, regardless of maternal genotype, and had lower insulin sensitivity. This phenotype was more pronounced in IL-6(-/-) offspring of IL-6(-/-) dams, because they gained weight significantly faster than IL-6(-/-) offspring of IL-6(+/-) dams and had more body fat and higher serum leptin levels at an earlier age. The leptin content was 2-fold higher in milk from IL-6(-/-) than WT dams. However, cross-fostering IL-6(-/-) mice with WT dams did not alter body weight, body composition, or adipocyte size at adult age compared with IL-6(-/-) mice fostered by IL-6(-/-) dams. Conversely, WT mice fostered by IL-6(-/-) dams weighed significantly more than those fostered by WT dams and had more body fat, larger adipocytes, and altered hypothalamic gene expression. We conclude that body fat of adult mice can be increased by perinatal exposure to factors affected by lack of maternal IL-6.

Molecular Characterisation of Transport Mechanisms at the Developing Mouse Blood–CSF Interface: A Transcriptome Approach

“…Some are important because they act as carriers, for example, thyroid hormone transporters. The main ones so far described, Slc16a2 (MCT8) and Slco1c1 (Oatp14), have recently been identified in cerebral endothelial and choroid plexus epithelial cells of rat fetuses [52]. In the present study the expression levels of these transports were similar in E15 and adult choroid plexus, as were many other transporters in the MCT and Oatp families ( Table S3 ).…”

“…In the present study the expression levels of these transports were similar in E15 and adult choroid plexus, as were many other transporters in the MCT and Oatp families ( Table S3 ). Another thyroid hormone transporter Slc16a10 (TAT1, MCT10; [52]) showed strikingly high expression in embryonic choroid plexus ( Table 6 ). However, Slc16a10 has been previously reported as undetectable in the adult brain [53].…”

A maternal diet of fatty fish reduces body fat of offspring compared with a maternal diet of beef and a post‐weaning diet of fish improves insulin sensitivity and lipid profile in adult C57BL/6 male mice

“…The method has been previously described (Lager et al . ). Within each group (herring, n = 4; beef, n = 11), the samples were pooled.…”

“…Catheters were inserted into the left carotid artery for blood sampling and into the right jugular vein for glucose and insulin infusions as previously described (Lager et al . ). After the clamp, mice were killed with pentobarbiturate, and white adipose tissue from the gonadal, peri‐renal and inguinal fat depots, anterior (interscapular) BAT (iBAT), liver and skeletal muscle from the hind leg (soleus) were separated, weighed, frozen at −80 °C and conserved in formalin.…”

Intergenerational Cycle of Obesity and Diabetes: How Can We Reduce the Burdens of These Conditions on the Health of Future Generations?

“…However, these last results were not replicated in culture conditions [77]. Moreover, fetal adiposity was positively correlated to maternal IL-6 [78], and adult offspring born to IL-6-deficient dams were heavier, had increased adiposity, decreased insulin sensitivity and leptin concentration [79]. IL-6-deficient mice presented reduced leptin concentration in their milk and wild type cross-fostered to IL-6-deficient mice had increased weight and adipocyte size and showed altered hypothalamic gene expression.…”