title: 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.
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Box 434, 405 30 Gothenburg, Sweden. susanne.lager@gu.se
authors.forename: Susanne
authors.initials: S
authors.lastname: Lager
authors.forename: Ingrid Wernstedt
authors.initials: IW
authors.lastname: Asterholm
authors.forename: Erik
authors.initials: E
authors.lastname: Schéle
authors.forename: Nina
authors.initials: N
authors.lastname: Jansson
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.forename: John-Olov
authors.initials: JO
authors.lastname: Jansson
authors.forename: Malin
authors.initials: M
authors.lastname: Lönn
authors.forename: Agneta
authors.initials: A
authors.lastname: Holmäng
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050154:Adiposity / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001823:Body Composition / Q000235:genetics / Q000502:physiology*; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015309:Glucose Clamp Technique; D007031:Hypothalamus / Q000378:metabolism; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008892:Milk / Q000737:chemistry; D011247:Pregnancy; D012333:RNA, Messenger
chemical_list: D015850:Interleukin-6; D020738:Leptin; D012333:RNA, Messenger