It shouldn’t come as a surprise to hear that obesity is one of the most prevalent medical concerns in the United States. In fact, 30% of the US population has obesity and 30% of these individuals also has diabetes. Our society is a point where the number of cases of type 1 diabetes in young people under the age of 18 is increasing. In order to combat this rise in obesity and diabetes regulations have been placed on fast food businesses, requirements such as food nutrition labels have been implemented, and grassroots campaigns against chemicals such as Red Dye and High Fructose Corn Syrup have sprung up around the country. These regulations have been put in place as an attempt to curb people’s eating habits and make them aware of just what they are eating. However, the issue of obesity and diabetes may not stem solely from society’s increased consumption of food. In order to understand the cause of these issues we must delve into the brain and observe the interactions of two chemicals: Leptin and Insulin.
While insulin is a term you’ve probably heard about, you may be unfamiliar with leptin. First, a brief summary of insulin. Insulin is a peptide hormone which regulates the amount of glucose taken in by cells throughout the body. Within the brain, insulin controls glucose intake by neurons, regulates acetylcholine, and contributes to memory function (http://www.hbo.com/alzheimers/science-insulin-in-the-brain.html). Similarly leptin is also a peptide hormone. Leptin is an important regulator of food intake (appetite) and body weight. In the brain leptin and insulin receptors are primarily found within the hypothalamus in a region known as the hypothalamic arcuate nucleus. Chemicals such as neuropeptide Y (NPY), agouti related protein (AgRP), and proopiomelanocortin (POMC), which are released based on leptin and insulin concentrations, cause the neurons in this region to be known as appetite-regulating neurons. When concentrations of insulin and leptin are high, POMC is released which reduces food intake and when concentration are low, NPY and AgRP stimulate food intake.
It might be helpful to know some of the Biochemistry of leptin signaling. Leptin stimulates cytokine receptors, which activate the JAK/STAT pathway towards gene expression. JAK, janus kinase, is a protein bound to the cytokine receptor, which upon stimulation of the receptor becomes phosphorylated. The phosphorylated JAK then creates a bind site for STAT (signal transducers and activators of transcription) molecules. STAT then enters the cell nucleus where it transcribes DNA for gene expression.
Now that some of the Biochemistry is out of the way, it is important to discuss how levels of leptin contribute to the rising levels of obesity in the US population. People with obesity have a flood of leptin in their system so the cytokine receptors become resistant to the overabundant leptin. This means that the appetite controlling chemical POMC is not produced because the neurons are not receiving leptin. Therefore, the signal stop food intake in never activated. On the other side of the metabolic disorder spectrum, people with anorexia have high levels of leptin without receptor resistance, thereby expressing POMC and preventing craving for food intake. Therefore, dyregulation and imbalance in leptin levels in the brain can cause various metabolic disorders such as obesity.