Pr. Johnson et al., LONGEVITY IN OBESE AND LEAN MALE AND FEMALE RATS OF THE ZUCKER STRAIN- PREVENTION OF HYPERPHAGIA, The American journal of clinical nutrition, 66(4), 1997, pp. 890-903
Zucker obese (fa/fa) and lean (Fa/Fa) rats were fed a soy protein diet
ad libitum under barrier conditions from 4 wk of age until death. Obe
se rats were also pair fed with lean controls to prevent hyperphagia.
Time of death was determined and tissues collected at necropsy for his
tologic examination. Lean rats had longer 10th percentile survivorship
(males 966 compared with 667 d, females 983 compared with 620 d) and
maximum life spans (males 1067 compared with 803 d, females 1163 compa
red with 744 d) than did obese rats. Preventing hyperphagia increased
maximum life span in both males (1010 d) and females (975 d). Patholog
ies in lean rats were similar to those reported for other rodent strai
ns. For obese rats fed ad libitum, end-stage renal disease (ESRD) was
the major cause of mortality (males: 91.1%, females: 93.3%). Preventio
n of hyperphagia decreased deaths attributable to ESRD (males: 64.4%,
females: 51.1%). A smaller restriction in energy intake (8-18%) requir
ed to prevent hyperphagia compared with the 35-40% in most other studi
es produced similar increases in longevity, suggesting that obese Zuck
er rats are particularly sensitive to energy restriction. Amelioration
of early onset of renal disease is a likely explanation. Percentage b
ody fat in food-restricted obese rats did not differ from that of anim
als fed ad libitum; thus, reduced longevity is not the result of obesi
ty per se, but rather is influenced by other metabolic pathologies occ
urring in this strain of rats homozygous for the Sa gene. Because micr
oalbuminuria with progression to ESRD is a complication in human obesi
ty, the Zucker strain offers the opportunity to investigate initiating
mechanisms of this pathology.