CR extent vs. benefit

[Guest guest]

Hi All,

The effects of different levels of CR on the pathological effects of overeating

seem

to be outlined in the not pdf-available paper below.

Keenan KP, Hoe CM, Mixson L, McCoy CL, JB, Mattson BA, Ballam GA,

Gumprecht

LA, Soper KA.

Diabesity: a polygenic model of dietary-induced obesity from ad libitum

overfeeding

of sprague-dawley rats and its modulation by moderate and marked dietary

restriction.

Toxicol Pathol. 2005;33(6):650-74.

PMID: 16207639

This study compared the effects of ad libitum (AL) overfeeding and moderate or

marked dietary restriction (DR) on the pathogenesis of a metabolic syndrome of

diabesity comprised of age-related degenerative diseases and obesity

in a outbred stock of Sprague-Dawley (SD) rats [Crl:CD (SD) IGS BR]. SD rats

were

fed Purina Certified Rodent Diet AL (group 1), DR at 72-79% of AL (group 2), DR

at

68-72% of AL (group 3) or DR at 47-48% of AL (group 4) for 106 weeks. Interim

necropsies were performed at 13, 26, and 53 weeks, after a 7-day

5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Body weights, organ

weights, carcass analysis, in-life data including estrous cyclicity, and

histopathology were determined.

At 6-7 weeks of age SD rats had 6% body fat. AL-feeding resulted in

hypertriglyceridemia, hypercholesterolemia, and dietary-induced obesity (DIO) by

study week 14, with 25% body fat that progressed to 36-42% body fat by 106

weeks. As

early as 14 weeks, key biomarkers developed for spontaneous nephropathy,

cardiomyopathy, and degenerative changes in multiple organ systems. Early

endocrine

disruption was indicated by changes in metabolic and endocrine profiles and the

early development and progression of lesions in the pituitary, pancreatic

islets,

adrenals, thyroids, parathyroids, liver, kidneys, and other tissues.

Reproductive

senescence was seen by 9 months with declines in estrous cyclicity and

pathological

changes in the reproductive organs of both sexes fed AL or moderate DR, but not

marked DR. The diabesity syndrome in AL-fed, DIO SD rats was readily modulated

or

prevented by moderate to marked DR. Moderate DR of balanced diets resulted in a

better toxicology model by significantly improving survival, controlling adult

body

weight and obesity, reducing the onset, severity, and morbidity of age-related

renal, endocrine, metabolic, and cardiac diseases. Moderate DR feeding reduces

study-to-study variability, increases treatment exposure time, and increases the

ability to distinguish true treatment effects from spontaneous aging. The

structural

and metabolic differences between the phenotypes of DIO and DR SD rats indicated

changes of polygenic expression over time in this outbred stock. AL-overfeeding

of

SD rats produces a needed model of DIO and diabesity that needs further study of

its

patterns of polygenic expression and phenotype.

Al Pater, PhD; email: old542000@...

__________________________________

- PC Magazine Editors' Choice 2005

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