Overnutrition, uncontrolled organ growth and apoptosis

Recently, we demonstrated, in vitro, that the products of excess energy intake, i.e., excess saturated fatty acids, activate both cell growth and cell death (apoptosis, DNA fragmentation). We have extended these findings to in vivo systems. We show that increased growth and accumulation of DNA fragments occur in most organs of ad libitum-fed animals obtained from three mouse models of degenerative diseases in adult animals: glomerulonephritis in NZB/NZW F₁ and MRL/n strains, the induction of lymphadenopathy by retrovirus LP-BM5 in C57BL/6J mice and induction of obesity in C57BL/6J mice fed a high fat diet. With the virus, changes are most marked in lymphoid organs in the C57BL/6J strain. With the obesity model, essentially all organs, including aorta, are affected, both in the C57BL/6J strain and also in the glomerulonephritic NZB/NZW F₁ and MRL/n strains. In addition, we showed that these lesions, as well as the DNA fragmentation, can be reversed in 2 to 4 weeks by restricting energy intake to 65% of ad libitum feeding or by exercise sufficient to remove storage fat. These observations suggest that excessive organ growth in mature animals, as activated by either excessive energy input or by retrovirus, leads eventually to excessive nucleosome endonuclease activity with resultant cell death.