Differential Effects of 25-Hydroxyvitamin D3 versus 1α 25-Dihydroxyvitamin D3 on Adipose Tissue Browning in CKD-Associated Cachexia

Patients with chronic kidney disease (CKD) often have low serum concentrations of 25(OH)D3 and 1,25(OH)2D3. We investigated the differential effects of 25(OH)D3 versus 1,25(OH)2D3 repletion in mice with surgically induced CKD. Intraperitoneal supplementation of 25(OH)D3 (75 μg/kg/day) or 1,25(OH)2D3 (60 ng/kg/day) for 6 weeks normalized serum 25(OH)D3 or 1,25(OH)2D3 concentrations in CKD mice, respectively. Repletion of 25(OH)D3 normalized appetite, significantly improved weight gain, increased fat and lean mass content and in vivo muscle function, as well as attenuated elevated resting metabolic rate relative to repletion of 1,25(OH)2D3 in CKD mice. Repletion of 25(OH)D3 in CKD mice attenuated adipose tissue browning as well as ameliorated perturbations of energy homeostasis in adipose tissue and skeletal muscle, whereas repletion of 1,25(OH)2D3 did not. Significant improvement of muscle fiber size and normalization of fat infiltration of gastrocnemius was apparent with repletion of 25(OH)D3 but not with 1,25(OH)2D3 in CKD mice. This was accompanied by attenuation of the aberrant gene expression of muscle mass regulatory signaling, molecular pathways related to muscle fibrosis as well as muscle expression profile associated with skeletal muscle wasting in CKD mice. Our findings provide evidence that repletion of 25(OH)D3 exerts metabolic advantages over repletion of 1,25(OH)2D3 by attenuating adipose tissue browning and muscle wasting in CKD mice.

Perirenal White Adipose Tissue Browning and Epithelial-Mesenchymal Transition, Contributes To Tumor Development in Kidney Cancer

Tumor cells can interact with neighboring adipose tissue and adipocyte dedifferentiation appears to be an important aspect of tumorigenesis. We evaluated the size of adipocytes in human adipose explants from normal (hRAN) and kidney cancer (hRAT); changes in the expression of WAT and BAT/beige markers in hRAN and hRAT; and changes in the expression of epithelial-mesenchymal transition (EMT) cell markers; in human kidney tumor (786-O, ACHN and Caki-1) and non-tumor (HK-2) epithelial cell lines incubated with the conditioned media (CMs) of hRAN and hRAT. We observed that hRAT adipocytes showed a significantly minor size compared to hRAN adipocytes. Also, we observed that both Prdm16 and Tbx1 mRNA and the expression of UCP1, TBX1, PPARγ, PCG1α, c/EBPα LAP and c/EBPα LIP was significantly higher in hRAT than hRAN. Finally, we found an increase in vimentin and N-cadherin expression in HK-2 cell incubated for 24 h with hRAT-CMs compared to hRAN- and control-CMs. Furthermore, desmin and N-cadherin expression also increased significantly in 786-O when these cells were incubated with hRAT-CMs compared to the value observed with hRAN- and control-CMs. The results obtained, together with the results previously published by our group, allow us to conclude that perirenal white adipose tissue browning and epithelial-mesenchymal transition, contributes to tumor development in kidney cancer.

Cold Hardiness of Select Apple Cider Cultivars in Canada

There is increasing interest in growing European origin apple cultivars for the production of hard cider in Canada; however, little is known about their winter hardiness. Eleven promising cider cultivars were evaluated for cold hardiness over two consecutive winters and compared with the winter tender cultivar 'Golden Delicious’. Sections of the current season's dormant shoots were frozen in a series of test temperatures ranging from -20°C to -40°C in a programmable freezer. Xylem tissue browning ratings were used to assess injury after thawing. The temperature of incipient damage (TID), the warmest temperature at which 1-yr-old shoot segments begin to show injury, was obtained from tissue browning curves using non-linear regression. TID varied significantly among cultivars and between sampling years. Overall, the cultivars could be classified according to relative winter hardiness as follows: Ashmead’s Kernel, Bramley’s Seedling (very tender) < Calville Blanc d’Hiver, Porter’s Perfection, Bulmer’s Norman (intermediate) < Crimson Crisp, GoldRush, Golden Delicious, Enterprise, Yarlington Mill, Enterprise (hardy) < Golden Russet (hardy). These data indicate nearly a 10oC range in winter hardiness amongst the 11 cultivars studied, depending on the sampling date. Ashmead’s Kernel and Bramley’s Seedling appear to be particularly winter tender, whereas Bulmer's Norman, Porter's Perfection, and Calville Blanc d'Hiver demonstrated less hardiness during three of the four sampling dates. Based upon these findings, it would be prudent to consult long-term climate normals and consider the frequency of extreme weather events for potential susceptibility to winter injury, particularly prior to establishing more injury-prone cultivars.

Enzymatic Browning in Banana Blossoms and Techniques for Its Reduction

Banana blossoms are rich in fiber and nutrients and are a popular plant-based, vegan alternative to fish. However undesirable browning, usually visible at the peduncle cut-end, negatively impacts consumer acceptability of banana blossoms. The aim of this work was to develop safe alternatives to prevent browning in banana blossoms. First, the activities of primary enzymes associated with tissue browning, i.e., polyphenol oxidase (PPO), peroxidase (POD) and phenylalanine ammonia lyase (PAL), were assayed. Our data showed that PPO and POD were the key enzymes responsible for blossom browning as they increased in activity, reaching a maximum at pH 7, as browning developed. In contrast, PAL activity decreased, and total phenolic content did not change as browning progressed, indicating PAL was not induced by cutting and may not be involved in blossom browning. Second, to find antibrowning agents for banana blossoms that can substitute for the use of sodium metabisulfite (SMS), different organic acids of varying concentrations were tested. Among organic acids studied, treatment with 3% (w/v) oxalic acid was the most effective method and thus could be a safe substitution for SMS to prevent browning in banana blossoms.

Loss of Sirt6 in adipocytes impairs the ability of adipose tissue to adapt to intermittent fasting

Intermittent fasting (IF) is gaining popularity for its effectiveness in improving overall health, including its effectiveness in achieving weight loss and euglycemia. The molecular mechanisms of IF, however, are not well understood. This study investigated the relationship between adipocyte sirtuin 6 (Sirt6) and the metabolic benefits of IF. Adipocyte-specific Sirt6-knockout (aS6KO) mice and wild-type littermates were fed a high-fat diet (HFD) ad libitum for four weeks and then subjected to 12 weeks on a 2:1 IF regimen consisting of two days of feeding followed by one day of fasting. Compared with wild-type mice, aS6KO mice subjected to HFD + IF exhibited a diminished response, as reflected by their glucose and insulin intolerance, reduced energy expenditure and adipose tissue browning, and increased inflammation of white adipose tissue. Sirt6 deficiency in hepatocytes or in myeloid cells did not impair adaptation to IF. Finally, the results indicated that the impaired adipose tissue browning and reduced expression of UCP1 in aS6KO mice were accompanied by downregulation of p38 MAPK/ATF2 signaling. Our findings indicate that Sirt6 in adipocytes is critical to obtaining the improved glucose metabolism and metabolic profiles conferred by IF and that maintaining high levels of Sirt6 in adipocytes may mimic the health benefits of IF.