Conclusions
Blocking LCN2 restores metabolic health and normalizes the pattern of food consumption by normalizing LCN2 signalling in different brain regions.
Material and methods
4-week-old male C57BL/6 mice were used, divided into four experimental groups: intact, T2D, TD2/anti-LCN2, and T2D/IgG as isotype control. T2D was induced by low doses of streptozotocin and a high-carbohydrate diet. LCN2 blockade was performed by intraperitoneal administration of a polyclonal anti-LCN2 antibody. We analyzed metabolic parameters, food intake, feeding patterns, and serum LCN2 and leptin concentrations. In another group of intact or T2D mice, we analyzed the effect of blocking LCN2 and recombinant LCN2 on food consumption in a fasting-refeeding test and, the expression of cFOS and LCN2 in brain sections, specifically in the hypothalamus, piriform cortex, visceral area, arcuate nucleus and caudate-putamen.
Methods
4-week-old male C57BL/6 mice were used, divided into four experimental groups: intact, T2D, TD2/anti-LCN2, and T2D/IgG as isotype control. T2D was induced by low doses of streptozotocin and a high-carbohydrate diet. LCN2 blockade was performed by intraperitoneal administration of a polyclonal anti-LCN2 antibody. We analyzed metabolic parameters, food intake, feeding patterns, and serum LCN2 and leptin concentrations. In another group of intact or T2D mice, we analyzed the effect of blocking LCN2 and recombinant LCN2 on food consumption in a fasting-refeeding test and, the expression of cFOS and LCN2 in brain sections, specifically in the hypothalamus, piriform cortex, visceral area, arcuate nucleus and caudate-putamen.
Results
T2D caused an increase in serum LCN2, without alterations in Ad libitum feeding, but with changes in the feeding pattern associated with alterations in LCN2-cFOS signalling in hypothalamic and non-hypothalamic brain regions. Blocking LCN2 improved metabolic parameters, increased Ad libitum feeding, and restored the feeding pattern after fasting, which is associated with enhanced LCN2 signalling in the brain. Conclusions: Blocking LCN2 restores metabolic health and normalizes the pattern of food consumption by normalizing LCN2 signalling in different brain regions.