Obesity Paradox, Obesity Orthodox, and the Metabolic Syndrome: An Approach to Unity

Jesse Roth, Navneet Sahota, Priya Patel, Syed F Mehdi, Mohammad M Wiese, Hafiz B Mahboob, Michelle Bravo, Daniel J Eden, Muhammad A Bashir, Amrat Kumar, Farah Alsaati, Irwin J Kurland, Wunnie Brima, Ann Danoff, Alessandra L Szulc, Valentin A Pavlov, Kevin J Tracey, Huan Yang

Obesity and the accompanying metabolic syndrome are strongly associated with heightened morbidity and mortality in older adults. In our review of more than 20 epidemiologic studies of major infectious diseases, including leaders such as tuberculosis, community-acquired pneumonia, and sepsis, obesity was associated with better outcomes. A cause-and-effect relationship between over-nutrition and survival with infection is suggested by results of two preliminary studies of infections in mice, where high fat feeding for 8-10 weeks provided much better outcomes. The better outcomes of infections with obesity are reminiscent of many recent studies of "sterile" non-infectious medical and surgical conditions where outcomes for obese patients are better than for their thinner counterparts --- and given the tag "obesity paradox". Turning to the history of medicine and biological evolution, we hypothesize that the metabolic syndrome has very ancient origins and is part of a lifelong metabolic program. While part of that program (the metabolic syndrome) promotes morbidity and mortality with aging, it helps infants and children as well as adults in their fight against infections and recovery from injuries, key roles in the hundreds of centuries before the public health advances of the 20th century. We conclude with speculation on how understanding the biological elements that protect obese patients with infections or injuries might be applied advantageously to thin patients with the same medical challenges.