1. Wayne Gade, PhD, MT(ASCP)[⇑][1] 1. Associate Professor, Clinical Lab Science Program, University of Illinois Springfield, Springfield, IL 2. Jean Gade, MS, BS(RN) 1. Nurse Educator, Lincoln Prairie Behavioral Health, Springfield, IL 1. Address for Correspondence: Wayne Gade, Clinical Laboratory Science & Chemistry Departments, HSB Rm 314, One University Place, Springfield, IL 62703, wgade1{at}uis.edu, 217-725-6384. Modern societies suffer from an obesity epidemic, despite considerable societal pressure to be thin. The epidemic persists in spite of the widely accepted notion that obesity is unhealthy, unattractive, and shortens life expectancy. Conservation of energy (the first law of thermodynamics) tells us that obesity must result when caloric intake chronically exceeds caloric expenditures. Historically, physiologic control mechanisms suppressed appetite and promoted physical activity, enabling most people to avoid a positive energy balance. But what forces compel modern humans, the most intelligent and rational of beings, to chronically exceed their caloric requirements? In the first article, we compare the development of obesity to a “highway” whose destination is obesity. This “Highway to Obesity” has many “entrance ramps” that represent the many biological, genetic, and psychological factors that underlie overindulgence. We explore the genetic deficiencies and biological tendencies that predispose one toward obesity. In recent decades, these inherited tendencies toward obesity are more likely to be expressed, due to easy access to high calorie foods and decreased physical activity. Complete genetic deficiencies rarely occur and generally result in early-onset, morbid obesity. More commonly, obesity involves a gradually acquired dysregulation of hormonal systems that initially limit obesity. However, when these fragile feedback mechanisms become overwhelmed and fail, hormone resistance actually favors weight gain. Article one also examines the multitude of comorbidities associated with obesity. These include type II diabetes, atherosclerosis, hypertension, congestive heart failure, pulmonary disease, several forms of cancer; renal disease, liver and gall bladder diseases, polycystic ovarian syndrome, coagulation disorders,… [1]: #corresp-1