Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition

Ishikawa, T., Kitaura, Y., Kadota, Y. et al. Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition. Sci Rep 7, 39825 (2017). https://doi.org/10.1038/srep3982

Enhanced oleate uptake and lipotoxicity associated with laurate

Free fatty acids have been reported to induce cell death (lipotoxicity), but the effects depend on the carbon chain length and number of double bonds. Medium‐chain saturated fatty acids (MC‐SFAs), such as laurate, have less lipotoxicity than long‐chain saturated fatty acids (LC‐SFAs), such as palmitate. Monounsaturated fatty acids, such as oleate, have also been reported not only to exert cytotoxic effects, but also to reduce the lipotoxicity of LC‐SFA. However the interaction between MC‐SFA and oleate with respect to cell death is unclear. In this report, we found that lipotoxicity was enhanced by a combination of laurate and oleate relative to either fatty acid alone. The possible mechanisms involved were examined by measuring the production of reactive oxygen species, mitochondrial depolarization, caspase‐3 activity, and lipid droplet formation. Although the stress signals and cell death pathways were distinct among different cell types, we found a common phenomenon of enhanced lipid droplet formation in all cells tested. Using fluorescent‐ or radioisotope‐labeled fatty acids, we found that oleate, but not laurate, increased the uptake of fluorescent‐labeled fatty acids, and the combinatory effect was more efficient than with oleate alone. We also found that laurate increased oleate uptake, but the effect of oleate on laurate uptake varied among cell types. These results suggest that laurate enhances the influx rate of oleate, the increased intracellular concentration of which not only enhances lipid storage, but also induces cell death by lipotoxic stress responses, which vary according to cell type

Regulation of hepatic branched-chain α-ketoacid dehydrogenase complex in rats fed a high-fat diet

Branched-chain α-ketoacid (BCKA) dehydrogenase complex (BCKDC) regulates branched-chain amino acid (BCAA) metabolism at the level of BCKA catabolism. It has been demonstrated that the activity of hepatic BCKDC is markedly decreased in type 2 diabetic animal models. In this study, we examined the regulation of hepatic BCKDC in rats with diet-induced obesity (DIO). Rats were fed a control or a 60% of energy high-fat diet (HFD) for twelve weeks. Concentrations of blood components and the activities and protein amounts of hepatic BCKDC and its specific kinase (BDK) were measured. The concentrations of plasma glucose, insulin, and corticosterone were significantly elevated in DIO rats compared to those fed the control diet, suggestive of insulin resistance. Blood BCAA concentrations were not increased. The activity of hepatic BCKDC that was present in the active form in the liver was higher in DIO rats compared to controls, although the total activity and the enzyme amount were not different between two diet groups. The activity of hepatic BDK and the abundance of BDK bound to the BCKDC were decreased in DIO rats. The total amount of hepatic BDK was also significantly decreased in DIO rats. In rats made obese through HFD feeding, in contrast to prior studies in rat models of type 2 diabetes, hepatic BDK was down-regulated and thereby hepatic BCKDC was activated, suggesting that DIO promotes liver BCKA catabolism. In this model there was no evidence that increased blood BCAAs drive DIO-associated insulin resistance, since concentrations of BCAAs were not altered by DIO

Feeding of 1-Kestose Induces Glutathione-S-Transferase Expression in Mouse Liver

Functional food ingredients, including prebiotics, have been increasingly developed for human health. The improvement of the human intestinal environment is one of their main targets. Fructooligosaccarides (FOS) are oligosaccharide fructans that are well studied and commercialized prebiotics. 1-Kestose, one of the components of FOS, is considered to be a key prebiotic component in FOS. However, to our knowledge, no studies have been reported on the physiological efficacy of 1-Kestose regarding its anti-oxidative activity. In the present study, we examined the effects of dietary 1-Kestose on gene expression of antioxidative enzymes in the liver, kidney and epididymal adipose tissue of mice by quantitative RT-PCR (qRT-PCR). We demonstrated that a 1-Kestose-rich diet increased mRNA and enzymatic activity levels of glutathione-S-transferase (GST) in mouse liver. These results suggest the possibility that dietary 1-Kestose as a prebiotic may enhance antioxidative activity in mice

An Alteration in the Cecal Microbiota Composition by Feeding of 1-Kestose Results in a Marked Increase in the Cecal Butyrate Content in Rats - Fig 1

<p><b>(a)-(e). Photographs of the cecum with cecal contents in rats.</b> The cecum from each group of rats: (a) control, (b) 0.5%, (c) 1%, (d) 2.5%, (e) 5%. Bars: 2 cm.</p

Concentrations of isobutyrate, isovalerate, and valerate in cecal contents.

<p>Concentrations of isobutyrate, isovalerate, and valerate in cecal contents.</p