Long-term low-dose alcohol intake promotes white adipose tissue browning and reduces obesity in mice.

There are numerous pieces of evidence indicating that moderate alcohol intake has a protective effect on metabolic diseases. Our previous studies revealed that long-term low-dose alcohol intake resists high-fat diet (HFD) induced obesity. A process in which white adipose tissue can be stimulated and turned into heat-producing brown adipose tissue named white adipose browning is associated with energy expenditure and weight loss. In this study we aimed to investigate whether alcohol causes the browning of white adipose tissue and whether the browning of white adipose tissue is involved in the resistance to the occurrence of obesity caused by long-term low-dose alcohol intake. After eight months of alcohol feeding, the body weight of mice had no significant change, but the fat content and lipid deposition in the liver were reduced. Morphological observations revealed that the browning of white adipose tissue occurred. The white adipose tissue browning marker UCP1 gene and protein expression levels were increased and the expression of the PGC1-α/PPAR-α pathway protein and the P38 MAPK/CREB pathway protein was also elevated in the alcohol feeding group. Moderate alcohol drinking increased the secretion of the CXCL14 protein in inguinal subcutaneous adipose tissue, which drove the recruitment of M2 macrophages. Moderate alcohol drinking mice had faster lipid metabolism and slower lipid anabolism. In addition, we found that long-term low-dose alcohol intake prevented the increase of body weight, triglycerides, inflammation and energy expenditure decrease induced by HFD. Moderate alcohol consumption increased the expression of UCP1 and glucose uptake in the adipose tissue of the HFD group. In conclusion, our results show for the first time that alcohol can trigger the browning of white adipose tissue to counteract obesity.

Enhancement of Solubility, Purification, and Inclusion Body Refolding of Active Human Mitochondrial Aldehyde Dehydrogenase 2.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is predominantly linked with acetaldehyde detoxification in the second stage of alcohol metabolism. To intensively study ALDH2 function, a higher purity and uniform composition of the protein is required. An efficient Escherichia coli system for ALDH2 expression was developed by using His and a small ubiquitin-related modifier fusion tag. Most of the recombinant ALDH2s were expressed in the form of inclusion bodies. The ALDH2-enriched inclusion bodies were denatured with 6 M guanidine hydrochloride, and then ALDH2 was ultrafitrated. Finally, ALDH2 was successfully purified through affinity and gel filtration chromatography. The purified ALDH2 was finally preserved by the vacuum freeze-drying method, and its purity was determined to be higher than 95%, with a final media yield of 33.89 mg/L. The specific activity of ALDH2 was 6.1 × 104 U/mg. This work was the first to report pET-SUMO-ALDH2 recombinant plasmid expression in Escherichia coli, and the inclusion bodies were isolated and refolded. Finally, the purified ALDH2 had relatively higher purity, yield, and biological activity.