Nicotinamide riboside supplementation exerts an anti-obesity effect and prevents inflammation and fibrosis in white adipose tissue of female diet-induced obesity mice.

Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD+) precursor. We previously reported that NR supplementation prevented the development of liver fibrosis in male mice. However, whether NR exerts a similar effect in females is unknown. Therefore, we determined whether NR supplementation can prevent obesity-induced inflammation and fibrosis in the liver and white adipose tissue (WAT) by providing NAD+ in obese female mice. Female C57BL/6J mice at the age of 8 weeks (young) and 16 weeks (old) were fed a high-fat/high-sucrose/high-cholesterol diet (HF) or HF diet supplemented with NR at 400 mg/kg/d for 20 weeks. While NR had minor effects in young female mice, it significantly reduced body weight gain, fat mass, glucose intolerance, and serum cholesterol levels compared to the HF group in old females. Hepatic NAD+ level tended toward an increase in the NR group (P=.054), but NR did not attenuate serum alanine aminotransferase levels, steatosis, and liver fibrosis in old female mice. However, NR decreased weight and adipocyte size in gonadal WAT (gWAT) of old females. NR also reduced the number of crown-like structures and the expression of inflammatory genes, along with decreases in fibrogenic gene expression and collagen accumulation in gWAT compared with the HF group. Also, old mice fed NR showed increased metabolic rates, physical activity, and energy expenditure compared with the HF. Thus, our results indicated that NR supplementation exerted an anti-obesity effect and prevented the development of inflammation and fibrosis in the WAT of old, but not young, female mice with diet-induced obesity.

Partial characterization of chorionic gonadotropin-like binding sites from the bacteria Xanthomonas maltophilia.

The gram-negative bacterium, Xanthomonas maltophilia, has low- and high-affinity luteinizing hormone/chorionic gonadotropin (LH/CG)-binding sites, similar to the LH/CG receptor found in mammals. Although the low-affinity site binds both LH and human CG (hCG), the high-affinity site is specific for hCG. In the current investigation, these two binding sites were independently isolated from X. maltophilia for further characterization. To isolate functional binding sites, we developed a solubilization method using the detergent zwittergent 3,14 and high glycerol concentrations that allowed for the maintenance of ligand-binding integrity. Gel filtration experiments established molecular weights of 170 and 11.5 kDa for the two binding sites, which were supported by data from photoaffinity labeling and ultracentrifugation experiments. Gel filtration data also suggested the presence of a third binding site of 5.4 kDa. The 170-kDa site had a binding affinity of Kd = 12 x 10(-6) and bound both LH and hCG. The small molecular weight site had an affinity of Kd = 9.4 x 10(-8) and was CG specific. Collectively, these data demonstrate the presence of multiple hormone binding sites in X. maltophilia that differ in molecular size, binding affinity, and ligand specificity.