eLife 2020;9:e58949 https://elifesciences.org/articles/58949
In the mouse, the osteoblast-derived hormone Lipocalin-2 (LCN2) suppresses food intake and acts as a satiety signal. This study now shows that a meal challenge increases serum LCN2 levels in humans with normal or overweight, but not in those with obesity. Postprandial LCN2 serum levels correlate inversely with hunger sensation in challenged subjects. Brain PET scans show that injected radiolabelled recombinant human LCN2 (rh-LCN2) crosses the blood-brain barrier and localizes to the hypothalamus. Daily treatment of lean monkeys with rh-LCN2 decreased food intake by 21%, without overt side effects, suggesting that LCN2 may be a novel target for obesity treatment.
The lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids, retinoids, and lipids. They share limited regions of sequence homology and a common tertiary structure architecture. LCN2 is mainly produced by bone cells of mice and humans and acts on the paraventricular nucleus (PVN) of the hypothalamus as a satiety signal that is upregulated after feeding in mice to limit food intake. Studies in mice have shown that it reduces food intake and prevents weight gain, without leading to a slow-down in their metabolism. The authors claim that LCN2 acts as a signal for satiety after a meal, leading mice to limit their food intake, and it does this by acting on the hypothalamus. In people with overweight or obesity, but not in people with normal weight, LCN2 levels increased after a meal. Non-responders, who showed no increase in LCN2 after a meal, tended to have a larger waist circumference and higher BMI, body fat, increased blood pressure and increased blood glucose. After gastric bypass surgery and weight loss they increased their LCN2, suggesting re-sensitization of these subjects.They also show that LCN2 can cross the blood-brain barrier. Monkeys treated with LCN2 for a week had a 28% decrease in food intake.