Changes in Liver Structure and Function after Short-Term and Long-Term Treatment of Rats with Dehydroepiandrosterone

Bellei, Monica; Battelli, Daniele; Fornieri, C.; Mori, G.; Muscatello, Umberto; Lardy, Henry A.; Bobyleva, Valentina

doi:10.1093/jn/122.4.967

Cited by 36 publications

(23 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we could not document that DHEAS induced either carnitine levels or fatty acid metabolism in the osteoblast cultures. Thus, our findings suggest that DHEAS promotes protein production in osteoblasts through other mechanisms, such as increasing mitochondrial respiration [16,44], protein synthesis [18,45], and enzyme activities [17,18,46,47].…”

Section: Discussionmentioning

confidence: 85%

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

et al. 1999

View full text Add to dashboard Cite

Abstract. Age-related bone loss eventually leads to osteopenia in men and women. The etiology of age-related bone loss is currently unknown; however, decreased osteoblast activity contributes to this phenomenon. In turn, osteoblast proliferation and function is dependent on energy production, thus the loss of energy production that occurs with age may account for the deficient osteoblast activity. Carnitine and dehydroepiandrosterone-sulfate (DHEAS), both of which decline with age, promote energy production through fatty acid metabolism. Thus, we hypothesized that carnitine and DHEAS would increase osteoblast activity in vitro. Accordingly, we measured the effect of carnitine and DHEAS on palmitic acid oxidation as a measure of energy production, and alkaline phosphatase (ALP) activity and collagen type I (COL) as indices of osteoblast function in primary porcine osteoblast-like cell cultures. Carnitine (10 −3 and 10 −1 M) but not DHEAS (10 −9 , 10 −8 , and 10 −7 M) increased carnitine levels within the cells. Carnitine alone and in combination with DHEAS increased palmitic acid oxidation. Both carnitine and DHEAS alone and in an additive fashion increased ALP activity and COL levels. These results demonstrate that in osteoblast-like cells in vitro, energy production can be increased by carnitine and osteoblast protein production can be increased by both carnitine and DHEAS. These data suggest that carnitine and DHEAS supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss. Key words:Osteoblast -Carnitine -Dehydroepiandrosterone sulfate -Alkaline phosphatase -Collagen Type I.Bone loss is often divided into two broad mechanisms: (1) postmenopausal bone loss, characterized by increased osteoclast activity, and (2) age-related bone loss, characterized by decreased osteoblast activity. Osteoblast activity is dependent on energy production. Thus, it is plausible that the loss of energy production, which accompanies age, may account for decreased osteoblast activity. Most cells use both glucose and fatty acid oxidation pathways for ATP synthesis, although some cell types show a substrate preference. For instance, some studies have suggested that glucose is the major fuel substrate for bone [1,2]. However, more recent work indicates that cell populations enriched with osteoblast-like cells generate 40-80% of the energy demands through fatty acid oxidation [3]. Osteoblasts are responsible for bone formation and it follows that they maintain a high rate of ATP utilization to support the requisite protein synthesis. Cells with a high rate of protein synthesis generate ATP from fatty acid oxidation, the most efficient metabolic process for energy production [4][5][6]. Thus, modulation of fatty acid oxidation may regulate the amount of energy available for protein synthesis in osteoblasts.A number of factors are required for fatty acid oxidation. For example, carnitine is the requisite carrier for the transport of long-chain fatty acids across the inner mitochondrial membrane into...

show abstract

Section: Discussionmentioning

confidence: 85%

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

et al. 1999

View full text Add to dashboard Cite

show abstract

“…It is also relevant that the steroid hormone dehydroepiandrosterone (DHEA) is reported to induce hepatomegaly in rats (Bellei et al, 1992) and mice (Friedman et al, 1996). Hepatomegaly induced by the hormone in rat livers was associated with a significant increase in the size and number of hepatocyte peroxisomes and of peroxisomal marker enzymes catalase and fatty acyl CoA oxidase.…”

Section: Mechanistic Aspectsmentioning

confidence: 99%

Effect of feeding solanidine, solasodine and tomatidine to non-pregnant and pregnant mice

Friedman

Henika

Mackey

2003

Food and Chemical Toxicology

View full text Add to dashboard Cite

The aglycone forms of three steroidal glycoalkaloids-solanidine (derived by hydrolytic removal of the carbohydrate side chain from the potato glycoalkaloids a-chaconine and a-solanine), solasodine (derived from solasonine in eggplants) and tomatidine (derived from a-tomatine in tomatoes)-were evaluated for their effects on liver weight increase (hepatomegaly) in non-pregnant and pregnant mice and on fecundity in pregnant mice fed for 14 days on a diet containing 2.4 mmol/kg of aglycone. In non-pregnant mice, observed ratios of % liver weights to body weights (%LW/BWs) were significantly greater than those of the control values as follows (all values in % vs matched controls AES.D.): solanidine, 25.5 AE13.2; solasodine 16.8 AE 12.0; and tomatidine, 6.0 AE7.1. The corresponding increases in pregnant mice were: solanidine, 5.3 AE10.7; solasodine, 33.1 AE15.1; tomatidine, 8.4 AE 9.1. For pregnant mice (a) body weight gains were less with the algycones than with controls: solanidine, À36.1 AE14.5; solasodine, À17.9 AE14.3; tomatidine, À11.9 AE18.1; (b) litter weights were less than controls: solanidine, À27.0 AE 17.1; solasodine, À15.5 AE 16.8; tomatidine, no difference; (c) the %LTW/BW ratio was less than that of the controls and was significant only for solasodine, À8.7AE 13.7; and (d) the average weight of the fetuses was less than the controls: solanidine, À11.2 AE 15.2; solasodine, À11.4 AE 9.4; tomatidine, no difference. Abortion of fetuses occurred in five of 24 pregnant mice on the solanidine and none on the other diets. To obtain evidence for possible mechanisms of the observed in vivo effects, the four glycoalkaloids (a-chaconine, a-solanine, solasonine and a-tomatine) mentioned above and the aglycones solanidine and tomatidine were also evaluated in in vitro assays for estrogenic activity. Only solanidine at 10 mm concentration exhibited an increase in the MCF-7 human breast cancer cell proliferation assay. Generally, the biological effects of solanidine differ from those of the parent potato glycoalkaloids. Possible mechanisms of these effects and the implication of the results for food safety and plant physiology are discussed. Published by Elsevier Science Ltd.

show abstract

“…Hypertrophy of hepatocytes following treatment with DHEA has been attributed to proliferation of peroxisomes and mitochondria [9]. Antioxidant effects of DHEA have also been demonstrated [10].…”

Section: Introductionmentioning

confidence: 99%

“…However, in the studies cited above, various researchers have used different dose regimens and the routes of administration also differed [7,9,10,13,14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of dehydroepiandrosterone (DHEA) treatment on oxidative energy metabolism in rat liver and brain mitochondria. A dose–response study

Patel¹,

Katyare²

2007

Clinical Biochemistry

View full text Add to dashboard Cite

Changes in Liver Structure and Function after Short-Term and Long-Term Treatment of Rats with Dehydroepiandrosterone

Cited by 36 publications

References 20 publications

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

Effect of feeding solanidine, solasodine and tomatidine to non-pregnant and pregnant mice

Effect of dehydroepiandrosterone (DHEA) treatment on oxidative energy metabolism in rat liver and brain mitochondria. A dose–response study

Contact Info

Product

Resources

About