Comparison of the effects of 20 days and 15 months of calorie restriction on male Fischer 344 rats

Dean, D. J.; Gazdag, A. C.; Wetter, Thomas J.; Cartee, Gregory D.

doi:10.1007/bf03339792

Cited by 21 publications

(19 citation statements)

References 15 publications

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“…They do not develop either hypertension or overt diabetes even under ad libitum-fed conditions (24). Thus, we are not concerned with superimposed overt diabetes or hypertension in considering these data, although, as would be expected, ad libitum-fed Fischer rats do have higher insulin levels than calorie-restricted rats (44). The calorie-restricted and ad libitum-fed rats are maintained under identical conditions until after weaning, at which time glomerular development is complete.…”

Section: Discussionmentioning

confidence: 90%

Podocyte Hypertrophy, “Adaptation,” and “Decompensation” Associated with Glomerular Enlargement and Glomerulosclerosis in the Aging Rat

Wiggins¹,

Goyal²,

Sanden³

et al. 2005

Journal of the American Society of Nephrology

338

281

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Whether podocyte depletion could cause the glomerulosclerosis of aging in Fischer 344 rats at ages 2, 6, 17, and 24 mo was evaluated. Ad libitum-fed rats developed proteinuria and glomerulosclerosis by 24 mo, whereas calorie-restricted rats did not. No evidence of age-associated progressive linear loss of podocytes from glomeruli was found. Rather, ad libitum-fed rats developed glomerular enlargement over time. To accommodate the increased glomerular volume, podocytes principally underwent hypertrophy, whereas other glomerular cells underwent hyperplasia. Stages of hypertrophy through which podocytes pass en route to podocyte loss and glomerulosclerosis were identified: Stage 1, normal podocyte; stage 2, nonstressed podocyte hypertrophy; stage 3, "adaptive" podocyte hypertrophy manifest by changes in synthesis of structural components (e.g., desmin) but maintenance of normal function; stage 4, "decompensated" podocyte hypertrophy relative to total glomerular volume manifest by reduced production of key machinery necessary for normal podocyte function (e.g., Wilms' tumor 1 protein [WT1], transcription factor pod1, nephrin, glomerular epithelial protein 1, podocalyxin, vascular endothelial growth factor, and ␣5 type IV collagen) and associated with widened foot processes and decreased filter efficiency (proteinuria); and stage 5, podocyte numbers decrease in association with focal segmental glomerulosclerosis. In contrast, in calorie-restricted rats, glomerular enlargement was minor, significant podocyte hypertrophy did not occur, podocyte machinery was unchanged, there was no proteinuria, and glomerulosclerosis did not develop. Glomerular enlargement therefore was associated with podocyte hypertrophy rather than hyperplasia. Hypertrophy above a certain threshold was associated with podocyte stress and then failure, culminating in reduced podocyte numbers in sclerotic glomeruli. This process could be prevented by calorie restriction.

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Section: Discussionmentioning

confidence: 90%

Podocyte Hypertrophy, “Adaptation,” and “Decompensation” Associated with Glomerular Enlargement and Glomerulosclerosis in the Aging Rat

Wiggins¹,

Goyal²,

Sanden³

et al. 2005

Journal of the American Society of Nephrology

338

281

View full text Add to dashboard Cite

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“…This does not preclude the possibility that alterations in glucoregulatory endpoints initiated by short-term energy restriction occur by the same mechanism(s) of action as those observed with long-term DR. Alternatively, it is possible that very subtle alterations in body fat or its distribution after initiation of DR, undetectable by conventional methods, may be central to or may work in tandem with other factors that together contribute to the mechanism(s) by which DR enhances insulin sensitivity. Changes in insulin-and glucoserelated variables have often been observed before alterations in body composition can be detected, shortly after initiation of DR in several species (29,39,47,48), suggesting that DR may alter these values, at least in part, independently of a reduction in fat mass. Perhaps early DR-induced alterations in levels of cytokines or other adipose tissue secretory products (11,33,52,56) may be important to the mechanism by which DR exerts its effects on insulin sensitivity (6).…”

Section: Perspectivesmentioning

confidence: 99%

Insulin sensitivity and glucose effectiveness from three minimal models: effects of energy restriction and body fat in adult male rhesus monkeys

Gresl¹,

Colman²,

Havighurst³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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. Insulin sensitivity and glucose effectiveness from three minimal models: effects of energy restriction and body fat in adult male rhesus monkeys. Am J Physiol Regul Integr Comp Physiol 285: R1340-R1354, 2003. First published July 3, 2003 10.1152/ ajpregu.00651.2002The minimal model of glucose disappearance (MINMOD version 3; MM3) and both the onecompartment (1CMM) and the two-compartment (2CMM) minimal models were used to analyze stable isotope-labeled intravenous glucose tolerance test (IVGTT) data from year 10 of a study of the effect of dietary restriction (DR) in male rhesus monkeys. Adult monkeys were energy restricted (R; n ϭ 12) on a semipurified diet to ϳ70% of control (C) intake (ad libitum-fed monkeys; n ϭ 12). Under ketamine anesthesia, fasting insulin levels were greater among C monkeys. Insulin sensitivity estimates from all models were greater in R than C monkeys, whereas glucose effectiveness estimates were not consistently greater in R monkeys. Fasting plasma glucose as well as hepatic glucose production and clearance rates did not differ between groups. Body fat, in part, statistically mediated the effect of DR to enhance insulin sensitivity indexes. Precision of estimation and intermodel relationships among insulin sensitivity and glucose effectiveness estimates were in the ranges of those reported previously for humans and dogs, suggesting that the models may provide valid estimates for rhesus monkeys as well. The observed insulin sensitivity indexes from all models, elevated among R vs. C monkeys, may be explained, at least in part, by the difference in body fat content between these groups after chronic DR.

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“…Hormone alteration seems to be a critical factor for cancer prevention by weight control due to the significant role of hormones in regulating cellular growth. Previous researchers have found that the levels of insulin (13), IGF-1 (14 -16), and leptin (14 -17) decreased significantly in DCR-fed mice.…”

mentioning

confidence: 96%

Effects of Dietary Calorie Restriction or Exercise on the PI3K and Ras Signaling Pathways in the Skin of Mice

Xie

Jiang

Ouyang

et al. 2007

Journal of Biological Chemistry

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Weight control by exercise and dietary calorie restriction (DCR) has been associated with reduced cancer risk, but the underlying mechanisms are not well understood. This study was designed to compare the effects of weight loss by increasing physical activity or decreasing calorie intake on tumor promoter-induced Ras-MAPK and PI3K-Akt pathways. SENCAR mice were randomly assigned to one of the following five groups: ad libitum-fed sedentary control, ad libitum-fed exercise (AL؉Exe), exercise but pair-fed at the amount as controls (PF؉Exe), 20% DCR, and 20% DCR plus exercise (DCR؉Exe). After 10 weeks, body weight and body fat significantly decreased in the groups of DCR, DCR؉Exe, and PF؉Exe when compared with the controls. AL؉Exe did not induce weight loss due to, at least in part, increased food intake. Plasma IGF-1 levels reduced significantly in DCR and DCR؉Exe but not PF؉Exe. The protein H-Ras and activated Ras-GTP significantly decreased in TPA-induced skin tissues of DCR-fed mice but not exercised mice. PI3K protein, phosphoserine Akt, and p42/p44-MAPK were reduced, however, in both DCR and PF؉Exe groups. Immunohistochemistry demonstrated that the significantly reduced H-Ras occurred in subcutaneous fat cells, while the reduced PI3K and PCNA took place only in the epidermis. Plasma leptin decreased in PF؉Exe, DCR, and DCR؉Exe, while the caspase-3 activity increased in DCR؉Exe only. Genomic microarray analysis further indicated that the expression of 34 genes relevant to PI3K and 31 genes to the MAPK pathway were significantly regulated by either DCR or PF؉Exe treatments. The reduced PI3K in PF؉Exe mice was partially reversed by IGF-1 treatment. The overall results of this study demonstrated that DCR abrogated both Ras and PI3K signaling, which might inhibit TPA-induced proliferation and anti-apoptosis. Selective inhibition of PI3K by PF؉Exe but not AL؉Exe seems more attributable to the magnitude of the caloric deficit and/or body fat loss than diet versus exercise comparison.The National Health and Nutrition Examination Survey indicates growing rates of obesity in American adults and overweight children over the past 20 years (1). Numerous prospective and case-control studies associated with weight control and physical activity estimate that excess body weight and sedentary life style account for about 39% endometrial, 25% kidney, 11% colon, 9% postmenopausal breast cancer, and 5% total cancer incidence (2-3). It has been suggested that those 25% over normal weight have a 33% greater cancer risk than those who maintain ideal body weight (4). Therefore, for many individuals, it would be advisable to maintain weight within the normal range to reduce their risk of cancer.Overweight/obesity is recognized as a reflection of a positive energy state that results from either over-consumption of energy or low energy expenditure. There is ample evidence that weight control via decreasing calorie intake and/or increasing physical activity reduces cancer risk in animal models. For almost a century, dietary calorie restr...

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Comparison of the effects of 20 days and 15 months of calorie restriction on male Fischer 344 rats

Cited by 21 publications

References 15 publications

Podocyte Hypertrophy, “Adaptation,” and “Decompensation” Associated with Glomerular Enlargement and Glomerulosclerosis in the Aging Rat

Podocyte Hypertrophy, “Adaptation,” and “Decompensation” Associated with Glomerular Enlargement and Glomerulosclerosis in the Aging Rat

Insulin sensitivity and glucose effectiveness from three minimal models: effects of energy restriction and body fat in adult male rhesus monkeys

Effects of Dietary Calorie Restriction or Exercise on the PI3K and Ras Signaling Pathways in the Skin of Mice

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