Effect of Postweaning Feed Restriction on Adipose Cellularity and Body Composition in Polygenic Obese Mice

Abstract

The M16 line of mice, selected for rapid postweaning gain, exhibits polygenically controlled obesity and hyperphagia. The effect of limiting postweaning energy intake on the subsequent growth and development of obesity in M16 mice was investigated. Male mice from M16 and an unselected line (ICR) were provided either ad libitum or limited (congruent to 70% of ad libitum) feed during the rapid postweaning growth period from 4 to 6 weeks of age. Body weights (g) at 6 weeks of age were: ad libitum ICR (31.0 +/- 0.6), restricted ICR (23.8 +/- 0.7), ad libitum M16 (45.0 +/- 0.6) and restricted M16 (30.1 +/- 0.6). In both lines, restricted feed intake severely depressed body fat, lean, ash, and water at 6 weeks. In addition, percent triacylglycerol, fat cell size and number in the epididymal fat pads were lower. Restricted M16 and ICR mice showed a marked compensatory gain in all body components when subsequently fed ad libitum for 10 weeks. All measurements of adiposity at 16 weeks were similar for the restricted and ad libitum regimens within each line. The relative amounts of energy deposited as fat and lean between 4 and 16 weeks were not influenced by restricted feeding, but M16 mice deposited a larger proportion of energy as fat than as lean when compared with ICR mice. The results suggest that fat cell number is determined at a relatively early age in mice and is primarily under genetic control.

Dopaminergic dysregulation in mice selectively bred for excessive exercise or obesity

“…M16 mice are selected for increased growth and body mass at 3-6 weeks of age. During this developmental period, M16 mice display significant hyperphagia, which contributes to the obesity phenotype (Allan et al, 2004; Eisen and Leatherwood, 1978a; Eisen and Leatherwood, 1978b). Thus, decreased DA turnover in M16 mice may be evidence for hyperphagia-induced neuroadaptation within central reward pathways.…”

Functional genomic characterization of delipidation elicited bytrans-10,cis-12-conjugated linoleic acid (t10c12-CLA) in a polygenic obese line of mice

“…To more closely parallel the major human obesity condition, we utilized the M16 polygenic obese line of mice (18,50). The M16 line was selected over 27 generations for rapid postweaning gain from an outbred ICR albino population and exhibits positive correlated responses in body weight and percent body fat and is hyperglycemic and hyperinsulinemic (19,26). Thus we conducted a study using dietary t10c12-CLA as a probe in combination with a polygenic obese mouse model to identify candidate genes associated with adipose metabolism.…”

The M16 Mouse: An Outbred Animal Model of Early Onset Polygenic Obesity and Diabesity

“…Differences in body weights observed in these experiments were as expected, with M16 mice being heavier than ICR at all ages. Differences are slightly lower than reported from earlier experiments (13, 14, 16, 19). This may be due to drift or inbreeding, but these influences are confounded with potential effects of location and diet (Figure 8).…”

“…Results from this study demonstrate that the M16 line has increased liver weight relative to body weight and has greater amounts of regional and overall body fat when compared with ICR, confirming earlier studies (14, 15). Weight of BAT was lower in the M16 line, similar to results found earlier by Saxton et al (26).…”

“…An ICR control line was maintained in parallel, with random mating from generation to generation but maintaining a similar effective population size (11). Mice from the M16 line are larger at all ages and have increased body fat percentage, fat cell size, fat cell numbers, and organ weights when compared with ICR (12)(13)(14)(15). These mice also exhibit hyperpha-gia, accompanied by moderate obesity, and are hyperglycemic, hyperinsulinemic, and hypercholesterolemic (16).…”