Obesity as a Conditioning Factor for High-Altitude Diseases

Abstract

Obesity, a worldwide epidemic, has become a major health burden because it is usually accompanied by an increased risk for insulin resistance, diabetes, hypertension, cardiovascular diseases, and even some kinds of cancer. It also results in associated increases in healthcare expenditures and labor and economic consequences. There are also other fields of medicine and biology where obesity or being overweight play a major role, such as high-altitude illnesses (acute mountain sickness, hypoxic pulmonary hypertension, and chronic mountain sickness), where an increasing relationship among these two morbid statuses has been demonstrated. This association could be rooted in the interactions between obesity-related metabolic alterations and critical ventilation impairments due to obesity, which would aggravate hypobaric hypoxia at high altitudes, leading to hypoxemia, which is a trigger for developing high-altitude diseases. This review examines the current literature to support the idea that obesity or overweight could be major conditioning factors at high altitude.

Long-Term Intermittent Work at High Altitude: Right Heart Functional and Morphological Status and Associated Cardiometabolic Factors

“…It has been assumed by several authors that under CH or CIHH, individuals are prone to good metabolic features (Anderson and Honigman, 2011 ; Ezzati et al, 2012 ). However, recent evidence has shown that there is an increasing proportion of individuals with marked metabolic alteration (Mohanna et al, 2006 ), which would be related to chronic mountain sickness (Miele et al, 2016 ) and other altitude diseases (San Martin et al, 2017 ). In fact, our results support this observation; in this model of exposure, a rather high proportion (almost half of the subjects) displayed an altered lipid profile.…”

Lower Body Weight in Rats Under Hypobaric Hypoxia Exposure Would Lead to Reduced Right Ventricular Hypertrophy and Increased AMPK Activation

“…In our results, the degree of hypoxia was the most important variable because it determined the amount of food intake, although the difference was not significant between the CR and the AL in CH groups. Interestingly, AL groups, in both hypoxia conditions show a decrease of food-intake and a possible explanation could be attributed to the hypoxic stressor and its side effects (San Martin et al, 2017).…”

“…Conversely, the CIH groups eat differently under hypoxic stimuli. Those fed ad libitum eat 4.5 g; however, the CR group eat an average of 7.9 g. The AL groups could have been affected by anorexia and general malaise, as occurs in humans (acute mountain sickness), and particularly so when just slightly over a healthy body weight (as described by San Martin et al, 2017). Furthermore, the AL group maintained a substantial amount of fat tissue, which has an influence in insulin.…”

“…The impact of caloric restriction (CR) on inducing weight loss in cardiac hypertrophy has substantial clinical importance (Karwi et al, 2019). Recently, it has been reported in both humans and animal models that overweight and obesity influence highaltitude illness outcomes such as pulmonary hypertension (San Martin et al, 2017;Brito et al, 2018). Studies in mice show that CR is a potent dietary intervention to produce beneficial cardiac effects (Kobara et al, 2015;Melo et al, 2016) through AMPK activation, which plays an important role in cardioprotection (Shinmura et al, 2005(Shinmura et al, , 2008Chen et al, 2013).…”

Non-genetic Transgenerational Inheritance of Acquired Traits in Drosophila

“…Often, multiple conditions manifest themselves simultaneously in afflicted individuals, suggesting shared elements in disease pathology. Obesity and other metabolic disorders, for example, are associated with various secondary disease indications as the underlying cellular and organismal metabolism is fundamental to nearly all necessary biological processes [45]. The prominent role of nutrition and other environmental factors in the development of metabolic disorders offers a promising model to identify and characterize the underlying epigenetic mechanisms, leading to diet optimization and nutrition-responsive therapies to combat chronic diseases (cf.…”