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PubMed2001

Caloric restriction mimetics: physical activity and body composition changes.

As the only paradigm that has consistently increased life span and inhibited the onset and/or progression of disease, dietary restriction has multiple effects on a variety of organ systems. In this brief review, the goal of the panel was to attempt to understand the role of changes in physical activity and body composition as possible modulators of the life span in experimental animals and humans. We focus on whether changes in exercise behavior and body composition produce similar changes as those found in dietary restriction and whether these changes can be used to either replace or enhance the beneficial effects of dietary restriction. The complexity of the two stimuli is emphasized in our report, with suggestions offered on how to better interpret existing research. Our panel briefly examines evidence in experimental animals and humans about the specific contributions of each of these factors to altering life span and age-related pathologies. We also discuss additional animal studies and/or human intervention studies that could be performed to clarify these issues. Finally, we provide suggested avenues for future research in this area of changes in physical activity and body composition as dietary restriction mimetics.

Animals↗
PubMed1981

Effects of medroxyprogesterone acetate and caloric restriction on the distribution of serum and liver lipids and proteins in female rats.

The effects of a large dose (2 mg/100 g body weight) of medroxyprogesterone acetate (MPA), restricted feeding (50% of normal intake) and their interaction were investigated on the serum and liver lipid and protein distribution in female rats. MPA increased serum cholesterol and triglyceride levels in rats on ad libitum food intake without having any effect in the animals on restricted diet. There was no statistical difference in the total serum protein or albumin levels among the groups. The serum levels of alpha and gamma globulin were significantly lower in the underfed rats. MPA increased the concentration of gamma globulin in well nourished rats but interacted with dietary restriction to further reduce the level of this protein in the undernourished animals. There was no difference in the levels of hepatic phospholipids or free cholesterol among groups, However, cholesterol ester and triglyceride levels in liver were significantly elevated in the MPA-treated group fed ad libitum. A similar increase was not found in underfed rats. This study indicates that MPA exerts significant effects on the distribution of serum and hepatic lipids and serum globulin levels and that the effects are dependent upon the nutritional status of the subject.

Alpha-Globulins↗
PubMed1983

Prolonged effects of fasting-refeeding on rat adipose tissue lipoprotein lipase activity: influence of caloric restriction during refeeding.

We studied lipoprotein activity in white adipose tissue of male rats during a 3-day fast and up to 21 days of refeeding. Changes in LPL were considered in relation to concomitant changes in fat cell size. During fasting fat cell size decreased and LPL activity declined markedly (80%). With ad libitum refeeding LPL activity returned to control values by 3 or 5 days of refeeding, increased above control values (60-100%) by 10 days of refeeding and returned to control values by 20 days of refeeding. The normalization and overshoot of LPL activity preceded and accompanied increases in fat cell size, which occurred between days 5 and 10 of refeeding; LPL activity returned to control values Only after fat cell size also returned to control values. Mild food restriction (approximately 25%) during refeeding allowed LPL activity to return to control values but reduced the magnitude and duration of the overshoot. Severe food restriction (approximately 50%) during refeeding delayed the return of LPL activity to control values until day 20 of refeeding. These data support a role for LPL in restoration of adipocyte lipid stores during refeeding. Food restriction during refeeding influences LPL and may modulate the rate of lipid accumulation by adipocytes during refeeding.

Adipose Tissue↗
PubMed1983

Novel regulation of lipoprotein lipase activity in rat brown adipose tissue: effects of fasting and caloric restriction during refeeding.

We studied the effects of a 3-day fast and 20 days of refeeding on lipoprotein lipase activity (LPL) in the interscapular brown adipose tissue (BAT) of sexually mature male rats. Rats were refed either ad libitum or restricted quantities (75 or 50% of normal ad libitum food intake). BAT-LPL, expressed on a per depot basis, decreased with fasting and returned to control values by day 3 of refeeding ad libitum. In contrast, refeeding restricted quantities for 5 to 20 days limited regain of body weight and increased BAT-LPL significantly above the values observed in rats refed ad libitum. These adaptations in BAT-LPL activity differ markedly from those observed in rat white adipose tissue or heart muscle and may serve to increase the supply of fatty acids from circulating lipoproteins for BAT metabolic needs and maintenance of thermogenesis during undernutrition.

Adipose Tissue, Brown↗
PubMed1998

Effects of maternal caloric restriction and exercise during lactation.

In affluent populations, breast-feeding women often wish to return to their prepregnancy weight as soon as possible postpartum and may restrict energy intake or increase exercise to achieve this goal. Gradual weight loss (< or = 2 kg/mo) seems to have no adverse effect on milk volume or composition, provided that the mother is not undernourished and is breast-feeding her infant on demand. Aerobic exercise improves cardiovascular fitness and does not affect milk energy transfer to the infant, but exercise alone is not likely to increase the rate of weight loss unless dietary intake is controlled. Less information is available on the effect of rapid weight loss. Data from a recent randomized intervention trial indicate that a short-term (11 d) energy deficit of 35%, achieved by dieting or a combination of dieting and increased exercise, results in weight loss > 1 kg/wk and does not adversely affect lactation. Exercise enhances maintenance of lean body mass and is therefore a recommended component of any weight loss program. Maternal plasma prolactin concentration generally increases under conditions of negative energy balance, which may serve to protect lactation. Further research is required on the longer-term effect of energy restriction and on the effects of energy balance in lactating women with low fat reserves.

Diet, Reducing↗
PubMed1999

Caloric restriction and experimental carcinogenesis.

Investigation into the influence of energy restriction in cancer has gone through 3 distinct periods. After the initial observation by Moreschi in 1909, there was about a decade of active research in this area. Then interest waned, possibly because the field had gone as far as it could, considering the knowledge and methodology available at the time. Interest was rekindled in 1940 due, principally, to the work coming from the laboratories of Tannenbaum at the Michael Reese Hospital in Chicago and Baumann at the University of Wisconsin. Another decade of active research followed. In this period, we learned how to design experimental diets and interest was expressed in dietary constituents. By 1950, publications on this type of research had dwindled and the field lay virtually dormant for 30 years. Since the early 1980's, research on this topic has blossomed and we now know enough about physiology and molecular biology to probe the mechanisms underlying the phenomenon. Energy flux, as in exercise, also inhibits carcinogenesis. Energy restriction modulates oxidative DNA damage and enhances DNA repair. It is now apparent that energy restriction affects adrenal metabolism (as hypothesized by Boutwell in 1949), insulin metabolism, and various aspects of gene expression. Understanding the basic mechanisms should provide important insights into control of tumor proliferation.

Animals↗
PubMed1997

Age does not affect thermal and cardiorespiratory responses to microwave heating in calorically restricted rats.

This study sought to determine whether age influences the thermal distribution and cardiorespiratory responses to 35 GHz microwave (MW) heating. Male Sprague-Dawley rats (n = 8/group) 3 to 4 mo old (young), 15 to 16 mo old (middle-aged), and 24 to 25 mo old (old) were used. All animals were restricted to 63% of ad libitum feed. Rats were anesthetized (ketamine) and a catheter was placed into a carotid artery for measurement of mean arterial blood pressure (MAP). Anesthetized rats were then exposed to MWs until death, while measuring MAP, heart rate and temperatures at five sites (colonic, left and right tympanic, subcutaneous, and tail). Before MW exposure, there were no significant (p < .05) differences among age groups in measured parameters. MW produced increases in temperature at each of the measured sites; temperatures at death did not differ between groups. Heart rate increased throughout MW exposure, in a statistically identical manner in all age groups. MAP was initially well maintained and then, in the latter phases of heating, precipitously declined until death, with no discernible age-related difference. Respiration rate was not altered by MW exposure in any group. Finally, there were no group differences in the MW exposure time required to induce death. Thus, age does not alter thermal and cardiorespiratory responses to 35 GHz MW heating in food-restricted rats.

Aging↗