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

Abstract

1Obesity paradox, obesity orthodox, and the metabolic syndrome: An approach to unity 1 Obesity paradox and the metabolic syndrome. Abstract: 26Obesity and the accompanying metabolic syndrome are strongly associated with heightened morbidity 27 and mortality in older adults. In our review of more than 20 epidemiologic studies of major infectious 28 diseases, including leaders such as tuberculosis, community-acquired pneumonia, and sepsis, obesity was 29 associated with better outcomes. A cause-and-effect relationship between over-nutrition and survival with 30 infection is suggested by results of two preliminary studies of infections in mice, where high fat feeding 31 for 8-10 weeks provided much better outcomes. The better outcomes of infections with obesity are 32 reminiscent of many recent studies of "sterile" non-infectious medical and surgical conditions where 33 outcomes for obese patients are better than for their thinner counterparts ---and given the tag "obesity 34 paradox". Turning to the history of medicine and biological evolution, we hypothesize that the metabolic 35 syndrome has very ancient origins and is part of a lifelong metabolic program. While part of that program 36 (the metabolic syndrome) promotes morbidity and mortality with aging, it helps infants and children as 37 well as adults in their fight against infections and recovery from injuries, key roles in the hundreds of 38 centuries before the public health advances of the 20th century. We conclude with speculation on how 39 understanding the biological elements that protect obese patients with infections or injuries might be 40 applied advantageously to thin patients with the same medical challenges. experts to predict that obesity will shortly become the leading personal health problem worldwide. 52Obesity and the accompanying metabolic syndrome are typically associated with shortened life 53 expectancy, premature disability, and heightened prevalence of cardiovascular disorders, cancer, diabetes, 54and Alzheimer disease as well as multiple other disorders linked to advancing age. 55 ( ¶2) In the jeremiads inspired by obesity, the modest but deeply rooted health advantages of 56 obesity are typically neglected (Table 1). In this paper we add further to the list of advantages of obesity; 57 we review over 20 epidemiology studies of six serious infectious diseases, including tuberculosis, 58 pneumonia, and sepsis, where outcomes are inversely related to body mass index. The consistency of the 59 obesity advantage is especially remarkable because the usual measurements to express adiposity i.e. body 60 mass index (BMI; the weight in kilograms divided by the square of the height in meters) as well as waist 61 circumference or neck circumference are such rough approximations of total body fat or of visceral fat or 62 of metabolic syndrome. The connection between body mass index and the metabolic syndrome in 63 epidemiology studies is further loosened by impressive ethnic differences (Figure 1) [1] and changes in 64 individuals with aging. ...

Reuniting overnutrition and undernutrition, macronutrients, and micronutrients

“…These disorders are considered to be consequences of the metabolic syndrome. While the late Gerald Reaven, a leader and pioneer in the field, focused on insulin resistance as a key element strongly related to obesity, later investigators emphasized elements of inflammation, eg, pro‐inflammatory cells and cytokines—in the etiology of the metabolic syndrome . Obesity, insulin resistance, and inflammation inter‐relate and interact on the path to the late chronic disorders …”

“…The negative effects of obesity are linked to the metabolic syndrome . The health benefits associated with obesity are often treated with suspicion and gathered under the rubric of the “obesity paradox.” The word “paradox” in the Oxford English Dictionary is “a statement or tenet contrary to received opinion or belief, especially one that is incredible, absurd, or fantastic.” Thus, the name “obesity paradox” given to the health benefits of obesity can be misleading. Benefits are not really paradoxical to the detrimental health effects of overweight.…”

“…Our hypothesis is that the link between nutrition and inflammation is essentially lifelong (“metabolic program”). Throughout life, bountiful nutrition helps fight infections and speeds wound healing (Figures ) . In youth, the benefits of extra nutrition are great and deficits small.…”

“…The life‐lengthening benefit of diminished weight reaches an optimum. Further decrements in body weight are associated with an upswing in mortality . The original explanation for the upswing at lower weights (inclusion of smokers or individuals with pre‐existing illnesses) has been discarded .…”

Obesity altered T cell metabolism and the response to infection

“…Roth et al., in their review of over 20 epidemiological studies, found that obesity was associated with better outcomes from infections such as tuberculosis, community-acquired pneumonia and sepsis [39]. They argue that aspects of the metabolic syndrome often found in obesity provide an advantageous niche for immune cells to fight off infection.…”