Preparation of a hydrolyzed yeast ß-glucan chromium(III) complex and evaluation of its hypoglycemic activity and sub-acute toxicity.

Yeast ß-glucan (BYG) possesses extremely low solubility that has limited its applications. In this study, we hydrolyzed BYG using snail enzyme to obtain hydrolyzed yeast ß-glucan (HBYG) with desirable water solubility and hypoglycemic activity. On the basis of HBYG, HBYG­chromium(III) complex (HBYG-Cr) was synthesized. The molecular weight of the complex was 4.41 × 104 Da, and the content of trivalent chromium was 8.95 %. The hydroxyl groups of HBYG participated in the coordination and formed the chromium complex. The space conformations of HBYG exhibited remarkable changes after complex formation. HBYG-Cr existed mainly in an amorphous state and presented good dispersibility, and the surface was uneven. The hypoglycemic activity of HBYG-Cr was studied in db/db and C57 mice. The results showed that HBYG-Cr had good hypoglycemic activity. Histopathological studies demonstrated that the liver, kidney, pancreas, and skeletal muscle in the treatment group were significantly improved compared with those in the diabetic model group. The sub-acute toxicity of HBYG-Cr was studied in KM mice and the results indicated that the complex did not cause adverse reactions or toxic side effects. This study broadened the application of yeast ß-glucan and provided an important reference for the development of hypoglycemic functional foods and drugs.

BCAA-BCKA axis regulates WAT browning through acetylation of PRDM16.

The link between branched-chain amino acids (BCAAs) and obesity has been known for decades but the functional role of BCAA metabolism in white adipose tissue (WAT) of obese individuals remains vague. Here, we show that mice with adipose tissue knockout of Bcat2, which converts BCAAs to branched-chain keto acids (BCKAs), are resistant to high-fat diet-induced obesity due to increased inguinal WAT browning and thermogenesis. Mechanistically, acetyl-CoA derived from BCKA suppresses WAT browning by acetylation of PR domain-containing protein 16 (PRDM16) at K915, disrupting the interaction between PRDM16 and peroxisome proliferator-activated receptor-γ (PPARγ) to maintain WAT characteristics. Depletion of BCKA-derived acetyl-CoA robustly prompts WAT browning and energy expenditure. In contrast, BCKA supplementation re-establishes high-fat diet-induced obesity in Bcat2 knockout mice. Moreover, telmisartan, an anti-hypertension drug, significantly represses Bcat2 activity via direct binding, resulting in enhanced WAT browning and reduced adiposity. Strikingly, BCKA supplementation reverses the lean phenotype conferred by telmisartan. Thus, we uncover the critical role of the BCAA-BCKA axis in WAT browning.

[Biotransformation of benzene to cis-1,2-dihydroxycyclohexa-3,5-diene using recombinant Escherichia coli JM109 (pKST11)].

Cis-1,2-dihydroxycyclohexa-3,5-diene (DHCD) can be used as a valuable chiral intermediates for applications in pharmaceuticals, aerospace, electrical and fine chemical industries. By on-line detection of toluene dioxygenase (TDO) activity in whole recombinant Escherichia coli JM109 (pKST11) cells that harbored TDO gene under a tac promoter, effects of IPTG and various benzene addition strategies on bioransformation of benzene to DHCD were investigated. When IPTG was used at the beginning of fermentation, the growth of cells was inhibited and TDO activity only maintained for 4 hours while same experiments with addition of IPTG at 6h or 8h generated TDO activity for 18 hours. Suitable induction time for IPTG was in the cell logarithmic growth phase and 0.5 mmol/L IPTG was sufficient for inducing maximum TDO activities. Benzene strongly inhibited the activity of TDO which catalyses the conversion of benzene to DHCD. It was found that both cell growth and TDO activity was remarkably inhibited by feeding of benzene vapor, only 7.5 g/L DHCD was obtained. While the benzene inhibition effect was ameliorated by two-liquid phase culture fermentation in which liquid paraffin was used as second phase in the broth. Using different initial ratios of paraffin to benzene in fed-batch culture, DHCD contents were increased to 22.6 g/L, which was 3-fold more compared with that in benzene vapor culture. A further improvement of DHCD production was achieved when the mixture of liquid paraffin and benzene was added continuously by peristaltic pump, the DHCD contents were increased to a final concentration of 36.8 g/L. It was proven that the key to improving DHCD production by recombinants is to prolong TDO activity in cells, which can be achieved by using suitable addition benzene strategies.