Effects of litter size and subsequent gold-thioglucose-induced obesity on adipose tissue weight, distribution and cellularity in male and female mice: an age study

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Abstract
1. Over- or undernutrition of newborn mice was caused by suckling in litters consisting initially of four or eighteen pups. After weaning mice were fedad lib. At 13 weeks of age some mice from large litters received gold thioglucose (GTG: 600 mg/kg intraperitoneally) to induce hyperphagia, and mice were killed at 13, 19·5, 26, 39 and 52 weeks.2. Total carcass lipid and the size and number of adipocytes in the inguinal subcutaneous, genital, perirenal and mesenteric depots were determined.3. Mice, both male and female, raised in small litters were heavier and had more carcass fat at all ages than mice raised in large litters. After GTG-treatment mice from large litters were heavier and fatter than mice raised in small litters.4. Fat distribution between the depots was related to carcass lipid content and not to treatment. The order of depot development was subcutaneous, parametrial, perirenal and mesenteric in females and epididymal, subcutaneous, perirenal and mesenteric in males. At 13 weeks the depots in males were more developed than those in females.5. Litter size had no effect on adipocyte volume in female mice at 13 weeks but by 52 weeks small-litter mice had larger cells in all depots and more cells in the parametrial and perirenal depots.6. Male mice from small litters had bigger cells at 13 weeks in all depots compared with males from large litters but by 52 weeks no significant differences remained. Greater numbers of cells were present only in the perirenal and mesenteric depots of small-litter males at some ages.7. Depots of GTG-treated large-litter female mice had larger cells than those of small-litter females, while a similar number of cells was found by 52 weeks in all but the perirenal depot, which had significantly more cells.8. GTG treatment of male mice from large litters also caused bigger cells than in small-litter mice, and an increased depot cell number at earlier ages in all but the epididymal depot. By 52 weeks cell numbers were similar in depots from small-litter and GTG-treated large-litter mice, except for the epididymal depot from the latter which had fewer cells.9. Increases in cell numbers with age in different depots occurred independently of existing cell mean volume and even of tissue growth, suggesting the presence of an in-built chronology, at least in older mice.10. We suppose that the differences in response to the level of preweaning nutrition in males and females result from a greater effect on the hypothalamic appetite centre in the latter. Whereas the cellular changes in large-litter males occur in the late-developing depots and are reversed naturally with time, those in the large-litter females are more extensive and require induction of hyperphagia for reversal.