Extension of the mitochondria dysfunction hypothesis of metabolic syndrome to atherosclerosis with emphasis on the endocrine‐disrupting chemicals and biophysical laws

Abstract

Metabolic syndrome and its component phenotypes, hyperglycemia, hypertension, (abdominal) obesity and hypertriglyceridemia, are major risk factors for atherosclerosis. Recently, associations between exposure to endocrine-disrupting chemicals (EDCs), mitochondrial dysfunction, metabolic syndrome and atherosclerosis have been established, suggesting a possible common mechanism underlying these phenomena. Extending a previously proposed mitochondria dysfunction theory of metabolic syndrome and using biophysical laws, such as metabolic scaling, Murray's law and fractal geometry of the vascular branching system, we propose that atherosclerosis could be explained as an ill-adaptive change occurring in nutrient-supplying arteries in response to the decreasing tissue energy demand caused by tissue mitochondrial dysfunction. Various aspects of this new hypothesis are discussed. (J Diabetes Invest,

Metabolic syndrome and the environmental pollutants from mitochondrial perspectives

“…We postulated in our previous paper that if the unit cellular metabolic rate is decreased due to accumulation of EDCs like POPs, adaptation would occur to restore core temperature, resulting in increased body mass [4]. This view is consistent with the view of Cannon and Nedergaard who emphasized the importance of thermogenesis [25].…”

“…Therefore we consider the mitochondria-based model of metabolic syndrome is a special case of metabolic scale law, which extend to mitochondrion itself and its electron transfer system [3,4]. Then, it must be stressed that this law is inevitable consequence of bioenergetics in large scale.…”

“…Adaptive thermogenesis or the auto-regulated production of heat in response to cold temperature or food intake is recognized as an important factor in determining weight maintenance. In this sense, mitochondria (dysfunction) hypothesis is a special case of the metabolic scaling relation occurring in humans [4].…”

“…We could not review this huge subject, but briefly review mitochondrial dysfunction hypothesis, in which mitochondrial dysfunction is a central pathophysiology of insulin resistance and the environmental pollutants are causes. For the details of this hypothesis, readers are referred to our previous reviews [3,4]. We fully acknowledge that this hypothesis is not well established.…”

Linking mitochondrial dysfunction, metabolic syndrome and stress signaling in Neurodegeneration

“…Recently, it has been reported that serum levels of many mitochondrial toxins, for instance, persistent organic pollutants (POPs) are associated with MetS. However, further investigation to reveal its precise mechanism is still unclear [9]. Likewise, deficiency of Co-enzyme Q10 (Co-Q10), an important element of the mitochondrial electron transport chain has been reported in a couple of clinical outcomes, including hypertension, heart failure, obesity, which all together leads to MetS [10].…”