Effect of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Alpha Variants on Spontaneous Clearance and Fibrosis Progression during Hepatitis C Virus Infection in Moroccan Patients

Virologica Sinica - Hepatitis C virus (HCV) is still one of the main causes of liver disease worldwide. Metabolic disorders, including non-alcoholic fatty liver disease (NAFLD), induced by HCV have...     

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 consequence of the lipid composition modifications in inner mitochondrial membrane leading to changes in BDH catalytic properties.     

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

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 results showed a high inhibition of BDH in terms of activity, protein expression and kinetic parameters.     

Characterization of two D-beta-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 mitochondrial membrane of heavy and light mitochondria. These changes could modify both BDH insertion and BDH lipid-dependent catalytic properties.     

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 possible key role of this ubiquitous isoform in the cold adaptation of this true hibernator. Inductions of PPARgamma(2) in WAT and PPAR beta/delta in BAT are blunted by a hypolipemic drug, the ciprofibrate. These changes may be correlated with hibernation arrest and death of treated jerboa. Mitochondrial acyl-CoA dehydrogenase and peroxisomal acyl-CoA oxidase activities in brown and white adipose tissues are decreased up to 85% during cold acclimatization (without food privation). These enzyme activities are subject to a strong induction in BAT and in WAT (3.4-7.5 fold) during the hibernation period. The BAT thermogenesis marker is also largely induced (approximately 4 fold of UCP1 mRNA level) during pre-hibernation period. Unexpectedly, treatment with ciprofibrate deeply affects lipolysis in BAT by increasing acyl-CoA dehydrogenase activity (3.4 fold) and acyl-CoA oxidase at both activity and mRNA levels (2.8 and 3.8 fold, respectively) and enhances strongly UCP1 mRNA level (9.5 fold) during pre-hibernation.     

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

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, both activities are decreased down to 85%. These enzymes activities are subject to a strong induction in brown and in white adipose tissue (3.4- to 7.5-fold, respectively) during the hibernation period which is characterized by a low body temperature (around 10 degrees C) and by starvation. Expression level of AOX mRNA and protein are increased during both pre-hibernation and hibernation periods. Unexpectedly, treatment with ciprofibrate, a hypolipemic agent, deeply affects lipolysis in brown adipose tissue by increasing acyl-CoA dehydrogenase activity (3.4-fold), both AOX activity and mRNA levels (2.8- and 3.8-fold, respectively) during pre-hibernation. Therefore, during pre-hibernation acclimatization, there is a negative regulation of fatty acid degradation allowing to accumulate a lipid stock which is later degraded during the hibernation period (starvation) due to a positive regulation of enzymes providing the required energy for animal survival.