Anti-COX4I1 monoclonal antibody, clone 31F9D23

To investigate the role of glucagon-like-peptide-1 receptor (GLP-1R) in peripheral lipid metabolism. Both lean and high-fat diet (HFD)-induced obesity (DIO) rats were used to compare the peripheral effects of the subcutaneous and repeated administration of the GLP-1R agonist liraglutide on the expression of key regulators involved in lipid metabolism, beta-oxidation and thermogenesis in liver, abdominal muscle, and epididymal white adipose tissue (eWAT). We observed that liraglutide reduced caloric intake, body weight, and plasma levels of triglycerides and VLDL in a diet-independent manner. However, changes in liver fat content and the expression of lipid metabolism regulators were produced in a diet and tissue-dependent manner. In lean rats, liraglutide increased the gene/protein expression of elements involved in lipogenesis (ChREBP, Acaca/ACC, Fasn/FAS, Scd1/SCD1, PPAR alpha/gamma), beta-oxidation (CPT1b), and thermogenesis (Cox4i1, Ucp1/UCP1) in eWAT and muscle, which suggest an increase in fatty-acid flux and utilization to activate energy expenditure. Regarding DIO rats, the specific reduction of liver lipid content by liraglutide was associated with a decreased expression of main elements involved in lipogenesis (phospho-ACC), peroxisomal b-oxidation (ACOX1), and lipid flux/storage (Ppar gamma/PPAR gamma) in liver, which suggest a recovery of lipid homeostasis. Interestingly, the muscle of DIO rats treated with liraglutide showed a decreased expression of PPAR gamma and the thermogenic factor UCP1. These results help us to better understand the peripheral mechanisms regulating lipid metabolism that underlay the effectiveness of GLP-1 analogues for the treatment of diabetes and obesity. (C) 2016 BioFactors

Tocotrienols (T3s) are a subgroup of vitamin E and they have been widely tested to inhibit cell growth in various tumor types. Previous studies have shown that T3s inhibit cancer cell growth by targeting multiple signaling transduction and cellular processes. However, the role of T3s in the regulation of cellular bioenergetic processes remains unclear. In this study, we found that gamma-T3 interacts with mitochondrial electron transfer chain NDUFB8 (a subunit of complex I) and SDHB (a subunit of complex II) and inhibits oxidative phosphorylation (OXPHOS), and triggers the production of reactive oxygen species (ROS). In addition, we observed that gamma-T3 upregulates the glycolytic capacity in cells, but it did not compensate for cellular ATP generation and decreased the ATP levels in cells. Furthermore, we performed western blots and RT-PCR to measure the mRNA and protein levels of mitochondrial electron transfer chain (ETC) proteins and complex V (ATP synthase), where the results indicated that gamma-T3 specifically inhibited the levels of NDUFB8 and SDHB, whereas it had little effect on UQCRC2 (a subunit of complex III), COX4I1 (a subunit of complex IV), and ATP5F1A (a subunit of complex V). The inhibition of NDUFB8 and SDHB by gamma-T3 led to the overproduction of ROS and the depletion of ATP, which may be responsible for inducing apoptosis in cancer cells. Our results suggest that mitochondria] respiration may be an effective target for anticancer treatments based on gamma-T3.