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…

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…

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 …

Peroxisomal changes during hiberation of jerboa (Jaculus orientalis)

As a member of the order of Rodentia, jerboa (Jaculus orientalis) is a natural deep hibernator and lives in subdesert highland in many parts of the world, including Morocco. Its small size (adult body weight ∼100 g), availability in the wild, tolerance to laboratory conditions, and some unique peroxisomal properties make it a suitable research subject for exploring peroxisome biogenesis under prehibernating and hibernating states. During 3 w, animals referred to as the prehibernator group were exposed to cold temperature (5 to 7°C) with food ad libitum. Part of the prehibernator group entered deep hibernation 24 to 48 h after starvation. Animals were sacrificed 4 and 6 d after starting hibe…

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…

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…

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…