Obesity is considered a public health problem in many parts of the world, and the rates of obesity are rising; the World Health Organization has called obesity a "global epidemic." While there is debate about what constitutes healthy body weight, and whether that may be different for different people, there is evidence that obese people are more likely to have other diseases including type 2 diabetes and heart disease. Obesity has also been linked to a reduction in life expectancy.
Hormones including leptin and ghrelin are produced by various organs and fat tissue. Those hormones can help regulate hunger and satiety, a feeling of fullness, by acting on neurons in the brain. The relationships among various hormones, the organs that produce them, and cells throughout the body, such as the hypothalamus-pituitary-adrenal axis, are very complex. Scientists have sought to understand them in various ways, and several new studies have revealed new findings that were discovered using human samples, animal models, and computational tools.
Reporting in the Proceedings of the National Academy of Sciences (PNAS), researchers found that a protein called augmentor-alpha is highly expressed in agouti-related peptide (AgRP) neurons in the hypothalamus. AgRP neurons are known to trigger feelings of hunger. In a mouse model, fasting caused AgRP neurons to generate more augmentor-alpha. While this work has to be confirmed in humans, the researchers suggested that augmentor-alpha plays a crucial role in energy conservation and metabolism, and may be involved in other processes as well.
A study reported in Cell Metabolism by a different group also focused on a molecule that stimulates AgRP neurons. This molecule, asprosin, promotes hunger by activating AgRP neurons. Previous research has indicated that asprosin raises the level of glucose in the blood through appetite stimulation. When people have lower asprosin levels, they are not as hungry and their glucose and insulin levels are lower.
This research identified the receptor for asprosin on AgRP neurons as protein tyrosine phosphatase receptor δ (Ptprd). When the researchers developed a drug that interfered with the link between Ptprd and asprosin, appetite and body weight was reduced in a mouse model.
"This new drug suppressed appetite, body weight, and blood glucose levels in obese mice by sequestering plasma asprosin. From a clinical standpoint, it means that this discovery could potentially yield a brand-new drug against metabolic syndrome," said first study author Ila Mishra, Ph.D., a research associate at Case Western Reserve School of Medicine. Now the researchers want to learn more about what other functions asprosin may perform.
In an unrelated study published in Frontiers in Endocrinology, scientists used mathematical modeling to analyze the relationship between two hormones in obese women. With a statistical approach called the Granger causality test, researchers analyzed the levels of cortisol, a stress hormone, and leptin, a hormone that promotes satiety in patients with obesity. Leptin also acts on neurons in the hypothalamus.
Though the study was very small, it indicated that in 14 of 18 patients, there was a reduction in leptin levels, which could be reducing satiety and raising their risk of obesity. The researchers suggested that a deeper understanding of the relationship between leptin and cortisol could help create new treatments for obesity.
Sources: Frontiers in Endocrinology, PNAS, University Hospitals Cleveland Medical Center, Cell Metabolism
