Abstract 299: Intestinal Apolipoprotein A-IV Expression Conserves Visceral Adiposity in Mice Subjected to Cyclical Feeding and Fasting

Background. We recently observed that although C57BL6 and apo A-IV knockout (A4KO) mice had similar weight gain on rodent chow, C56BL6 mice gained more weight and had greater adiposity when fed a high fat diet for 12 weeks (J Lipid Res 52:1984-1994, 2011). As food intake and intestinal fat absorption were the same in both groups, these data suggest that intestinal apo A-IV expression increases the efficiency of dietary energy storage. Here we have investigated whether apo A-IV could conserve adiposity in the setting of energy deprivation. Methods. Four month old male C56BL6 and A4KO mice (n=5) weighing ∼30-35 gm were subjected to repeated 3 day cycles of free access to a high fat (40%) diet alternating with access to only water. Intra-abdominal fat, fat free mass (FFM), and hepatic fat were measured at baseline and after 8 weeks by CT scanning. At the end of the study, livers and epidydimal fat pads were collected and weighed. Results. After 8 weeks on the feed-fast regimen, C57BL6 and A4KO mice had lost similar amounts of total weight, 4.4 ± 0.7 vs 5.2 ± 0.5 g (mean ± SE) and fat free mass, 3.0 ± 0.5 vs 3.0 ± 0.4 g; however, C57BL6 mice had lost less fat than A4KO mice, 1.4 ± 0.3 vs 2.2 ± 0.2 g (p=0.05). C57BL6 mice displayed a smaller decrease in adiposity than A4KO mice, 13.8 ± 1.1 to 10.9 ± 1.1 % vs 13.1 ± 0.5 to 7.9 ± 0.8 % (p=0.02 for the difference in the decrease between groups). There was a trend towards lower hepatic fat content (estimated from CT Hounsfield units) in C57BL6 mice, but liver (1.4 ± 0.2 vs 1.7 ± 0.2 g) and fat pad (1.3 ± 0.7 vs 1.1 ± 0.7 g) weights were not significantly different between the strains, suggesting that cyclical fasting affected mainly visceral fat. Conclusions. These data establish that intestinal apo A-IV expression conserves visceral adipose tissue during cyclical fasting. Because apo A-IV is a uniquely mammalian apolipoprotein which appeared at the time of the divergence of mammals from the avian-reptile lineages, and as the mammalian survival paradigm requires that sufficient stores of lipid energy are available to support thermogenesis, internal gestation, and lactation, these data suggest that a major role of apo A-IV is to promote energy storage during times of dietary energy surfeit and conserve lipid energy stores during periods of prolonged energy deprivation.