Anti-obesity activity has been reported for beta-carotene (BC) supplementation at high doses and metformin (MET). We studied whether BC treatment at a closer to dietary dose and MET treatment at a lower than therapeutic dose are effective in ameliorating unwanted effects of an obesogenic diet and whether their combination is advantageous. Obesity-prone mice were challenged with a high-fat diet (HFD, 45% energy as fat) for 4 weeks while receiving a placebo or being treated orally with BC (3 mg/kg/day), MET (100 mg/kg/day), or their combination (BC+MET); a fifth group received a placebo and was kept on a normal-fat diet (10% energy as fat). HFD-induced increases in body weight gain and inguinal white adipose tissue (WAT) adipocyte size were attenuated maximally or selectively in the BC+MET group, in which a redistribution towards smaller adipocytes was noted. Cumulative energy intake was unaffected, yet results suggested increased systemic energy expenditure and brown adipose tissue activation in the treated groups. Unwanted effects of HFD on glucose control and insulin sensitivity were attenuated in the treated groups, especially BC and BC+MET, in which hepatic lipid content was also decreased. Transcriptional analyses suggested effects on skeletal muscle and WAT metabolism could contribute to better responses to the HFD, especially in the MET and BC+MET groups. The results support the benefits of the BC+MET cotreatment.

We studied the effect of microbiota on the transcriptome and weight of the urinary bladder by comparing germ-free (GF) and specific pathogen-free (SPF) housed mice. In total, 97 genes were differently expressed (fold change > ±2; false discovery rate (FDR) p-value < 0.01) between the groups, including genes regulating circadian rhythm (Per1, Per2 and Per3), extracellular matrix (Spo1, Spon2), and neuromuscular synaptic transmission (Slc18a3, Slc5a7, Chrnb4, Chrna3, Snap25). The highest increase in expression was observed for immunoglobulin genes (Igkv1-122, Igkv4-68) of unknown function, but surprisingly the absence of microbiota did not change the expression of the genes responsible for recognizing microbes and their products. We found that urinary bladder weight was approximately 25% lighter in GF mice (p = 0.09 for males, p = 0.005 for females) and in mice treated with broad spectrum of antibiotics (p = 0.0002). In conclusion, our data indicate that microbiota is an important determinant of urinary bladder physiology controlling its gene expression and size.