The discovery of leptin, an appetite-suppressing hormone secreted by fat tissue, generated headlines and great hopes for an effective treatment for obesity. But hopes dimmed when it was found that obese people are unresponsive to leptin due to development of leptin resistance in the brain. New research, however, may revive that hope.

In 1995, researchers reported that they had isolated a protein that is present in normal mice, but not in an obese strain. When either obese or normal mice were directly injected with the protein, now called leptin, they ate less and lost weight. Unfortunately, when obese humans took the hormone, they lost weight only temporarily.

In a new study, scientists showed that the brain cells of obese mice have increased stress in the endoplasmic reticulum (ER), and that this stress blocks leptin action in the brain. But they also showed that reducing ER stress can re-sensitize the brain to leptin, and lead to weight loss when used in conjunction with leptin.