Different classes of fibres differ in their potential to lower lipid levels. In order to examine how chemically diverse fibres differ in their hypolipidaemic activity, mucilages of varying chemical composition isolated from three different sources were administered to experimental animals and the metabolism of lipids and lipoproteins was studied. The mucilages used were a galactomannan isolated from fenugreek (Trigonella foenum-graecum) seeds, a glucomannan from Dioscorea esculenta tubers and an arabinogalactan from Colocasia esculenta tubers. Rats were fed these mucilages at a dose of 4 mg/100 g body weight per d for 8 weeks and the changes in the levels of total cholesterol and triacylglycerols in serum, liver and aorta were analysed. All these mucilages decreased lipid levels both in serum and tissues. Among these mucilages, glucomannan showed the most hypolipidaemic effect followed by galactomannan and arabinogalactan. Further, hepatocytes were isolated from the livers of mucilage-fed rats and the synthesis and secretion of lipoproteins were studied using metabolic labelling. There was a decrease in the synthesis and secretion of apoB-containing lipoproteins, mainly VLDL, by hepatocytes isolated from mucilage-fed rats when compared to control (P<0.05). This was further confirmed by pulse chase analysis. Among the different mucilages, mannose-rich glucomannan showed the most effect followed by galactomannan, and mannose-free arabinogalactan showed minimal effect. Comparison of relative viscosity and water-holding capacity showed that mannan-rich mucilages like galactomannan and glucomannan, which showed greater hypolipidaemic effect, had greater relative viscosity and water-holding capacity. The present results suggested that the hypolipidaemic effect of dietary fibre involves a decrease in hepatic production of VLDL and further that it varies with the nature of the fibre.

The antihypercholesterolemic and antiatherogenic effect of the mucilage galactomannan isolated from fenugreek seeds was studied in experimental rabbits maintained on a high cholesterol diet for 3 months. Changes in the levels of cholesterol and triglycerides in serum and tissues and aortic fatty lesions were analysed in animals receiving mucilage (40 mg/kg body weight) daily and compared with the control. A significant decrease in serum total cholesterol, LDL cholesterol and triglycerides and cholesterol and triglycerides in liver and aorta and a decrease in Sudan IV staining of aorta indicated antihypercholesterolemic and antiatherogenic effects of the mucilage. Regression studies showed that administration of mucilage for 3 months caused a significant decrease in serum total and LDL cholesterol and aortic cholesterol. Mucilage accelerated the regression of atheromatous lesions in the aorta as evidenced by significantly low sudanophilic staining. Recovery from inflammation in hypercholesterolemic animals receiving mucilage was evidenced by a faster decrease in C-reactive protein (CRP) in serum to basal levels. The lipid lowering and antiatherogenic effects of mucilage from fenugreek which is used as a food flavoring spice highlights the importance of dietary intervention in the regression of atherosclerosis.

Hypothermic conditions enhance the incidence of cardiovascular diseases due to increased blood pressure. Cold-induced adaptive thermogenesis increased mitochondrial biogenesis and function in skeletal muscles and adipocytes. Here, we studied the effect of intermittent cold exposure on the regulators of cardiac mitochondrial biogenesis, function, and its regulation by SIRT-3. Intermittent cold exposed mice hearts showed normal histopathology with increased mitochondrial antioxidant and metabolic function, as evidenced by an increase in the activity and expression of MnSOD and SDH. A substantial increase in mitochondrial DNA copy number and increase in the expression of PGC-1α and its downstream targets NRF-1 and Tfam indicated the possibility of enhanced cardiac mitochondrial biogenesis and function on intermittent cold exposure. Increased mitochondrial SIRT-3 level and decreased total protein lysine acetylation indicate increased sirtuin activity in cold exposed mice hearts. Ex vivo cold mimic using norepinephrine showed a significant increase in PGC-1α, NRF-1, and Tfam levels. AGK-7, a SIRT-3 inhibitor, reversed the norepinephrine-induced upregulation of PGC-1α and NRF-1, indicating the role of SIRT-3 on the production of PGC-1α and NRF-1. Inhibition of PKA with KT5720 in norepinephrine treated cardiac tissue slices indicates the role of PKA in regulating the production of PGC-1α and NRF-1. In conclusion, intermittent cold exposure upregulated the regulators of mitochondrial biogenesis and function through PKA and SIRT-3 mediated pathway. Our results emphasize the role of intermittent cold-induced adaptive thermogenesis in overcoming chronic cold-induced cardiac damage.

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ADAMTS-4 is a protease enzyme which involves in vascular remodeling and atherosclerosis. It was found to be upregulated in macrophages seen in atherosclerotic lesions. The aim of this study was to investigate the expression and regulation of ADAMTS-4 in oxLDL induced human monocytes/macrophages system. PBMCs isolated from human blood(hPBMCs), treated with oxLDL (50μg/ml) were used as the model system for the study. mRNA and protein expressions were studied by qRT-PCR, ELISA, and western blot analysis. ROS production and cell viability were determined by fluorescence imaging and MTT assay respectively. In the presence of oxLDL, monocytes get differentiated into macrophages, which were confirmed by the increased expression of CD-36, b- D glucuronidase activity and by the morphological changes. OxLDL increased the mRNA and protein expression of ADAMTS-4 and TIMP-3 in monocytes/ macrophages. A significant increase in the mRNA and protein expression of TNF-α was also observed in oxLDL treated cells compared to untreated control. In the presence of NAC, the ROS scavenger, the production of NFκB and ADAMTS-4 was decreased significantly. Our study suggests that oxLDL significantly upregulated the expression of ADAMTS-4 in the monocyte/macrophage system. OxLDL mediated upregulation of ADAMTS-4 in hPBMCs involves TNF-α and ROS- NFκB pathway.

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Background and aimsADAMTS-4 is a protease enzyme involved in vascular remodeling and atherosclerosis. It was found to be upregulated in macrophages seen in atherosclerotic lesions. This study aimed to investigate the expression and regulation of ADAMTS-4 in oxidized LDL-induced human monocytes/macrophages system.MethodsPeripheral blood mononuclear cells (PBMCs) isolated from human blood, and treated with oxidized LDL (50 μg mL−1) were used as the model system for the study. mRNA and protein expressions were studied by PCR, ELISA, and western blot analysis. ROS production and cell viability were determined by DCFDA staining and MTT assay, respectively.ResultsIn the presence of oxidized LDL, monocytes get differentiated into macrophages, which were confirmed by the increased expression of macrophage differentiation markers and pro-inflammatory cytokine TNF-α. Oxidized LDL increased the mRNA and protein expression of ADAMTS-4 in monocytes/macrophages. N- Acetyl cysteine, ROS scavenger, downregulate the protein expression of ADAMTS-4. The expression of ADAMTS-4 was decreased significantly in the presence of NF-κB inhibitors. SIRT-1 activity was significantly downregulated in the macrophages and was reversed in the presence of the SIRT-1 agonist, resveratrol. Acetylation of NF-κB and hence the expression of ADAMTS-4 were significantly downregulated in the presence of SIRT-1 activator, resveratrol.ConclusionsOur study suggests that oxidized LDL significantly upregulated the expression of ADAMTS-4 in the monocytes/macrophages through ROS- NF-κB- SIRT-1 pathway.