Argan oil prevents down-regulation induced by endotoxin on liver fatty acid oxidation and gluconeogenesis and on peroxisome proliferator-activated receptor gamma coactivator-1 alpha, (PGC-1alpha), peroxisome proliferator-activated receptor gamma (PPARgamma) and estrogen related receptor alpha (ERRalpha)

In patients with sepsis, liver metabolism and its capacity to provide other organs with energetic substrates are impaired. This and many other pathophysiological changes seen in human patients are reproduced in mice injected with purified endotoxin (lipopolysaccharide, LPS). In the present study, down-regulation of genes involved in hepatic fatty acid oxidation (FAOx) and gluconeogenesis in mice exposed to LPS was challenged by nutritional intervention with Argan oil. Mice given a standard chow supplemented or not with either 6% (w/w) Argan oil (AO) or 6% (w/w) olive oil (OO) prior to exposure to LPS were explored for liver gene expressions assessed by mRNA transcript levels and/or enzyme a…

Sensitivity of liver metabolism in jerboa (Jaculus orientalis) to ciprofibrate, a peroxisome proliferator.

International audience; Ciprofibrate is a well-known drug used to normalize lipid parameters and fibrinogen in atherosclerosis patients. In laboratory rodents such as rats or mice, ciprofibrate exhibits peroxisome proliferator activity. However, to date, no clear alterations or side effects caused by ciprofibrate have been noted in humans. In order to further investigate such possible relationships, we studied the effects of sustained ciprofibrate treatment in jerboas (Jaculus orientalis). In these rodents, ciprofibrate does not induce hepatomegaly or promote liver cell DNA replication, confirming that this species more closely resembles humans than do rats or mice. The jerboas were treated…

Immunoaffinity purification and characterization of mitochondrial membrane-bound D-3-hydroxybutyrate dehydrogenase from Jaculus orientalis.

Abstract Background The interconversion of two important energy metabolites, 3-hydroxybutyrate and acetoacetate (the major ketone bodies), is catalyzed by D-3-hydroxybutyrate dehydrogenase (BDH1: EC 1.1.1.30), a NAD+-dependent enzyme. The eukaryotic enzyme is bound to the mitochondrial inner membrane and harbors a unique lecithin-dependent activity. Here, we report an advanced purification method of the mammalian BDH applied to the liver enzyme from jerboa (Jaculus orientalis), a hibernating rodent adapted to extreme diet and environmental conditions. Results Purifying BDH from jerboa liver overcomes its low specific activity in mitochondria for further biochemical characterization of the e…

Purification and characterization of the ?-β-hydroxybutyrate dehydrogenase from dromedary liver mitochondria

Abstract d -β-Hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a membrane enzyme, has been purified to homogeneity from dromedary ( Camelus dromedarius ) liver mitochondria. Our new purification method consisted of the solubilization of mitochondrial membranes by Triton X 100 and purification of BDH by two steps: DEAE-Sephacel and Phenyl-Sepharose. The molecular mass of the enzyme subunit size was 67 kDa. The purified enzyme is recognized by anti rat liver mitochondrial BDH antibodies. Furthermore, BDH activity was absolutely dependent upon phospholipids. BDH is also characterized by specific enzymatic parameters: an optimum pH of approximately 8 for the oxidation reaction, and approximat…

Changes of peroxisomal fatty acid metabolism during cold acclimatization in hibernating jerboa (Jaculus orientalis)

Abstract Jerboa (Jaculus orientalis) is a deep hibernator originating from sub-desert highlands and represents an excellent model to help to understand the incidence of seasonal variations of food intake and of body as well as environmental temperatures on lipid metabolism. In jerboa, hibernation processes are characterized by changes in the size of mitochondria, the number of peroxisomes in liver and in the expression of enzymes linked to fatty acid metabolism. In liver and kidney, cold acclimatization shows an opposite effect on the activities of the mitochondrial acyl-CoA dehydrogenase (–50%) and the peroxisomal acyl-CoA oxidase (AOX) (+50%), while in brown and white adipose tissues, bot…

Jerboa (Jaculus orientalis) is a deep hibernating rodent native to subdesert highlands. During hibernation, a high level of ketone bodies i.e. acetoacetate (AcAc) and D-3-hydroxybutyrate (BOH) are produced in liver, which are used in brain as energetic fuel. These compounds are bioconverted by mitochondrial D-3-hydroxybutyrate dehydrogenase (BDH) E.C. 1.1.1.30. Here we report, the function and the expression of BDH in terms of catalytic activities, kinetic parameters, levels of protein and mRNA in both tissues i.e brain and liver, in relation to the hibernating process. We found that: 1/ In euthemic jerboa the specific activity in liver is 2.4- and 6.4- fold higher than in brain, respective…

Nopal Cactus (Opuntia ficus-indica) as a Source of Bioactive Compounds for Nutrition, Health and Disease

Opuntia ficus-indica, commonly referred to as prickly pear or nopal cactus, is a dicotyledonous angiosperm plant. It belongs to the Cactaceae family and is characterized by its remarkable adaptation to arid and semi-arid climates in tropical and subtropical regions of the globe. In the last decade, compelling evidence for the nutritional and health benefit potential of this cactus has been provided by academic scientists and private companies. Notably, its rich composition in polyphenols, vitamins, polyunsaturated fatty acids and amino acids has been highlighted through the use of a large panel of extraction methods. The identified natural cactus compounds and derivatives were shown to be e…

Biochemical and histological alterations of cellular metabolism from jerboa (Jaculus orientalis) by 2,4-dichlorophenoxyacetic acid: Effects on d-3-hydroxybutyrate dehydrogenase

?; International audience; 2,4-Dichlorophenoxyacetic acid (2,4D) is one of the widely used herbicide of the phenoxy family with possible startling number of adverse effects on species other than the weeds which is designed to kill. The effects of 2,4D were investigated in jerboa (Jaculus orientalis), a wild animal of subdesert highlands. The jerboas have been daily treated intraperitonally with 2,4D 3 mg/kg body weight for 4 weeks. Plasmatic markers, and antioxidants defences systems were assessed and histological alterations were evaluated. The in vivo and in vitro effects of 2,4D on the mitochondrial D-3-hydroxybutyrate dehydrogenase (BDH) were also determined. Our results showed a strong…

Physiological, morphological and metabolic changes in Tetrahymena pyriformis for the in vivo cytotoxicity assessment of metallic pollution: Impact on d-β-hydroxybutyrate dehydrogenase

Abstract The individual cytotoxicity of cadmium chloride, iron sulphate and chromium nitrate has been investigated by using the freshwater ciliate Tetrahymena pyriformis. The metabolic enzymes and antioxidant defense biomarkers were assessed. The results obtained reveal that their metal salts have perturbed the physiology and morphology of T. pyriformis. Also, the biomarkers assessed were sensitive to the presence of metal salts and this sensitivity was metal salt and dose dependant. To estimate the impact of their metal salts on mitochondria, we studied their effects in vivo and in vitro on the d -β-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30) inner mitochondrial membrane enzyme. The …

Characterization of two d-β-hydroxybutyrate dehydrogenase populations in heavy and light mitochondria from jerboa (Jaculus orientalis) liver

Mitochondrial membrane-bound and phospholipid-dependent D-beta-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a ketone body converting enzyme in mitochondria, has been studied in two populations of mitochondria (heavy and light) of jerboa (Jaculus orientalis) liver. The results reveal significant differences between the BDH of the two mitochondrial populations in terms of protein expression, kinetic parameters and physico-chemical properties. These results suggest that the beta-hydroxybutyrate dehydrogenases from heavy and light mitochondria are isoform variants. These differences in BDH distribution could be the consequence of cell changes in the lipid composition of the inner mitochon…

D-3-hydroxybutyrate oxidation in mitochondria by D-3- Hydroxybutyrate dehydrogenase in Tetrahymena pyriformis

International audience; Tetrahymena pyriformis a ciliated protozoan, is considered a good indicator of water pollution. However its energy supply is poorly understood. This work was focused on the metabolism of hydroxybutyrate through the study of the membrane bound mitochondrial NAD+-dependent D-3-hydroxybutyrate dehydrogenase (EC. 1.1.1.30) (BDH), a ketone body catalysing enzyme involvedin the interconversion of D-3-hydroxybutyrate to acetoacetate. Due to lack of informations, the physico-chemical properties and kinetic parameters of the enzyme were examined. The results are the following: 1) D-3-hydroxybutyrate is a good substrate for mitochondria. 2) The enzyme catalytic process follows…

Protective Effect of Cactus Cladode Extracts on Peroxisomal Functions in Microglial BV-2 Cells Activated by Different Lipopolysaccharides

International audience; In this study, we aimed to evaluate the antioxidant and anti-inflammatory properties of Opuntia ficus-indica cactus cladode extracts in microglia BV-2 cells. Inflammation associated with microglia activation in neuronal injury can be achieved by LPS exposure. Using four different structurally and biologically well-characterized LPS serotypes, we revealed a structure-related differential effect of LPS on fatty acid β-oxidation and antioxidant enzymes in peroxisomes: Escherichia coli-LPS decreased ACOX1 activity while Salmonella minnesota-LPS reduced only catalase activity. Different cactus cladode extracts showed an antioxidant effect through microglial catalase activ…

Biological activities of Schottenol and Spinasterol, two natural phytosterols present in argan oil and in cactus pear seed oil, on murine miroglial BV2 cells

International audience; The objective of this study was to evaluate the biological activities of the major phytosterols present in argan oil (AO) and in cactus seed oil (CSO) in BV2 microglial cells. Accordingly, we first determined the sterol composition of AO and CSO, showing the presence of Schottenol and Spinasterol as major sterols in AO. While in CSO, in addition to these two sterols, we found mainly another sterol, the Sitosterol. The chemical synthesis of Schottenol and Spinasterol was performed. Our results showed that these two phytosterols, as well as sterol extracts from AO or CSO, are not toxic to microglial BV2 cells. However, treatments by these phytosterols impact the mitoch…

Peroxisome proliferator-activated receptors as regulators of lipid metabolism; tissue differential expression in adipose tissues during cold acclimatization and hibernation of jerboa (Jaculus orientalis).

Brown (BAT) and white (WAT) adipose tissues play a key role in the body energy balance orchestrated by the central nervous system. Hibernators have developed a seasonal obesity to respond to inhospitable environment. Jerboa is one of the deep hibernator originated from sub-desert highlands. Thus, this animal represents an excellent model to study cold adaptation mechanism. We report that the adipogenic factor PPARgamma exhibits a differential expression between BAT and WAT at mRNA level. A specific induction was only seen in WAT of pre-hibernating jerboa. Interestingly, PPAR beta/delta is specifically induced in BAT and brain of pre-hibernating jerboa, highlighting for the first time the po…

Modulation of peroxisomes abundance by argan oil and lipopolysaccharides in acyl-CoA oxidase 1-deficient fibroblasts

Pseudo-neonatal adrenoleukodystrophy (P-NALD) is a neurodegenerative disorder caused by acyl-CoA oxidase 1 (ACOX1) deficiency with subsequent impairment of peroxisomal fatty acid β-oxidation, accumulation of very long chain fatty acids (VLCFAs) and strong reduction in peroxisome abundance. Increase in peroxisome number has been previously suggested to improve peroxisomal disorders, and in this perspective, the present work was aimed at exploring whether modulation of peroxisomes abundance could be achieved in P-NALD fibroblasts. Here we showed that treatment with the natural Argan oil induced peroxisome proliferation in P-NALD fibroblasts. This induction was independent on activations of bo…

Prehibernation and hibernation effects on the D-3-hydroxybutyrate dehydrogenase of the heavy and light mitochondria from liver jerboa (Jaculus orientalis) and related metabolism.

The D-3-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30) from liver jerboa (Jaculus orientalis), a ketone body converting enzyme in mitochondria, in two populations of mitochondria (heavy and light) has been studied in different jerboa states (euthermic, prehibernating and hibernating). The results reveal: (1) important variations between states in terms of ketones bodies, glucose and lipid levels; (2) significant differences between the BDH of the two mitochondrial populations in term of protein expression and kinetic properties. These results suggest that BDH leads an important conformational change depending on the physiological state of jerboa. This BDH structural change could be the c…