Why might someone who is on a diet and eating very few molecules not lose weight?

Yet as we gain weight our bodies become less sensitive to leptin, and it becomes harder and harder to slim down. In other words, weight gain begets more weight gain. In an experiment using mice that became obese on a high-fat diet, an international team found obesity increases the activity of an enzyme called matrix metalloproteinase-2, or MMP-2. By using a technique called western blot analysis—separating and identifying all the proteins in a tissue sample—the authors found MMP-2 cleaves off a portion of the leptin receptor in the hypothalamus, impairing the hormone’s signaling and its ability to suppress appetite.