Prevention of obesity in A<sup>vy</sup>/a mice by dehydroepiandrosterone

Yen, Terence T.; Allan, J. A.; Pearson, D; Acton, J M; Greenberg, Mark M.

doi:10.1007/bf02533624

Cited by 235 publications

(80 citation statements)

References 23 publications

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“…In the case of DHEA supplementation for anti-obesity, it is not known if DHEA decreases abdominal obesity in humans as has been shown in laboratory animal studies (33,(42)(43)(44). The results of epidemiologic studies of the relationship between DHEA and abdominal fat have been conflicting.…”

Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone intake protects against 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in the obese Zucker rat model

Hakkak

Shaaf²,

Jo³

et al. 2010

Oncol Rep

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Abstract. Obesity has been epidemic in the US for over two decades; almost 65% of adults in the US are overweight. Obesity has been linked with the risk of development of various cancers, including breast cancer. Dehydroepiandrosterone (DHEA) is an over-the-counter dietary supplement used as an immunomodulating, anti-depressant, anti-aging, anti-cardiovascular disease, and anti-cancer agent and antiobesity supplement. The objectives of this study were to investigate the long-term effects of obesity and DHEA treatment on body weight gain and on 7,12-dimethylbenz(a)-anthracene (DMBA)-induced mammary tumor development. Forty-three six-week-old obese female Zucker rats were used. Rats were randomly assigned and had ad libitum access to water and a diet of either chow (2016) as a control diet or chow with the addition of DHEA at a concentration of 6 g/kg of chow as a DHEA diet. All rats were orally gavaged at age 50 days with 65 mg DMBA/kg body weight. Rats were weighed and palpated twice weekly for detection of mammary tumors and sacrificed 155 days post-DMBA treatment. Obese rats fed the DHEA diet gained significantly less weight than obese control diet rats (P<0.001). At the end of the experiment, 55% of the control diet group developed mammary tumors, while no tumors were detected in the DHEA diet group (P<0.001). Our results suggest that DHEA treatment can reduce body weight gain and protects against DMBA-induced mammary tumor development in the obese Zucker rat model.

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Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone intake protects against 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in the obese Zucker rat model

Hakkak

Shaaf²,

Jo³

et al. 2010

Oncol Rep

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“…Several studies report findings suggesting similarities between elevated levels of these steroids and the effects of CR. For example, DHEA treatment prevented obesity in mice (69), and altered tumorigenesis (70). Furthermore, reduced serum insulin is associated with increased DHEAS and lowered DHEAS is associated with increased cardiovascular disease (66).…”

Section: Biological Age Scorementioning

confidence: 99%

Beyond the rodent model: Calorie restriction in rhesus monkeys

Lane

Ingram

Roth

1997

AGE

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Lifespan extension and reduction of age-related disease by calorie restriction (CR) are among the most consistent findings in gerontological research. The well known effects of CR have been demonstrated many times in rodents and other short-lived species. However, effects of CR on aging in longerlived species, more closely related to humans, were unknown until recently. Studies of CR and aging using nonhuman primates (rhesus monkeys) were begun several years ago at the National Institute on Aging, the University of Wisconsin-Madison, and the University of Maryland. These studies are beginning to yield useful data regarding the effects of this nutritional intervention in primates. Several studies from these ongoing investigations have shown that rhesus monkeys on CR exhibit physiological responses to CR that parallel findings in rodents. In addition, several potential biomarkers of aging are being evaluated and preliminary findings suggest the possibility that CR in rhesus monkeys could slow the rate of aging and reduce age-related disease, specifically diabetes and cardiovascular disease. It will be several years before conclusive proof that CR slows aging and extends life span in primates is established, however, results from these exciting studies suggest the possibility that the anti-aging effects of CR reported in rodents also occur in longer-lived species such as nonhuman primates, strenghtening the possibility that this nutritional intervention will also prove beneficial in longer-lived species, including humans.

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“…Based on genetic mapping experiments (8,9), it was suspected (and subsequently proven) that the Zucker fatty mutation was in the same gene as the db mutation (10). The high likelihood that fa and/are mutations in the same gene was demonstrated by the obese phenotype offa/f compound mutants (11)(12)(13) and the recent molecular mapping of/to the same genomic interval as/a (13).…”

mentioning

confidence: 99%

Phenotype of the Obese Koletsky (f) Rat Due to Tyr763Stop Mutation in the Extracellular Domain of the Leptin Receptor (Lepr): Evidence for Deficient Plasma-to-CSF Transport of Leptin in Both the Zucker and Koletsky Obese Rat

et al. 1997

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The obese phenotypes of the diabetes (db) mouse and fatty (fa) rat are due to functional null mutations of the leptin receptor (Lepr). The recessive mutation in the Koletsky (f) obese rat maps to the same genetic intervals as db and fa and fails to complement the fa mutation. Comparison of the sequence of brain Lepr cDNA from +/+ and f/f animals reveals a T2349A transversion resulting in a Tyr763Stop nonsense mutation in the gene just before the transmembrane domain. Virtual absence of Lepr mRNA in whole brain from /^animals is consistent with the presence of a null mutation. The predicted reduced cerebrospinal fluid (CSF) transport of leptin in both f/f and fa/fa mutants is reflected in thẽ 10-fold lower ratio of CSF/plasma leptin concentration in the obese versus lean animals. However, equivalent CSF leptin concentration between lean and obese rats (fa/fa, f/f) indicates that leptin can enter the CSF through a non-Lepr-mediated mechanism, which may be saturated at normal physiological plasma leptin concentration. Diabetes 46:513-518, 1997 T he obese (ob) and diabetes (db) mutations have recently been shown to be in the Lep (leptin) and Lepr (leptin receptor) genes, respectively (1,2). Leptin is secreted from adipose tissue and is a ligand for the receptor whose five or more splice variants are expressed in a tissue-specific fashion (3,4). Because leptin (16 kDa) is produced only in adipose tissue and is too large to From the Laboratory of Human Behavior and Metabolism (X.S.W.-R, S.C.C., cross the blood-brain barrier, it is thought to enter the brain parenchyma via a saturable transport system, possibly constituted by one or more of the various membrane bound splice variants of Lepr.The identical phenotypes of ob and db mutant micewhich include early onset, severe obesity, insulin resistance, and strain-dependent diabetes-and the results of cross circulation experiments between ob and db animals provided the initial evidence that these were mutations in a signaling pathway for the size of body fat stores (5). Rats with a similar autosomal recessive phenotype were described first by Zucker et al. (fatty =/a) (6) and then by Koletsky (Koletsky =f) (7) in two different rodent colonies and rat strains. Based on genetic mapping experiments (8,9), it was suspected (and subsequently proven) that the Zucker fatty mutation was in the same gene as the db mutation (10). The high likelihood that fa and/are mutations in the same gene was demonstrated by the obese phenotype offa/f compound mutants (11-13) and the recent molecular mapping of/to the same genomic interval as/a (13).The recently cloned Lepr gene encodes a single transmembrane-spanning protein that resembles gpl30, a member of the class I cytokine receptor superfamily (1,14). The db and db Pas mutations have been shown to be, respectively, novel splice donor (3) and gene duplication (9) mutations in Lepr. The fa mutation is a Gln269Pro transversion in Lepr that impairs intracytoplasmic transport of the protein (10,15).In this report, we show that / is a nonsense ...

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Prevention of obesity in A^vy/a mice by dehydroepiandrosterone

Cited by 235 publications

References 23 publications

Dehydroepiandrosterone intake protects against 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in the obese Zucker rat model

Dehydroepiandrosterone intake protects against 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in the obese Zucker rat model

Beyond the rodent model: Calorie restriction in rhesus monkeys

Phenotype of the Obese Koletsky (f) Rat Due to Tyr763Stop Mutation in the Extracellular Domain of the Leptin Receptor (Lepr): Evidence for Deficient Plasma-to-CSF Transport of Leptin in Both the Zucker and Koletsky Obese Rat

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Prevention of obesity in Avy/a mice by dehydroepiandrosterone

Cited by 235 publications

References 23 publications

Dehydroepiandrosterone intake protects against 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in the obese Zucker rat model

Dehydroepiandrosterone intake protects against 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in the obese Zucker rat model

Beyond the rodent model: Calorie restriction in rhesus monkeys

Phenotype of the Obese Koletsky (f) Rat Due to Tyr763Stop Mutation in the Extracellular Domain of the Leptin Receptor (Lepr): Evidence for Deficient Plasma-to-CSF Transport of Leptin in Both the Zucker and Koletsky Obese Rat

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Prevention of obesity in A^vy/a mice by dehydroepiandrosterone