There is no doubt that the interaction between genetic and environmental (mainly dietary) factors plays a very significant role in the aetiology of many socially significant diseases. It should be noted that the human genome was originally selected in completely different living conditions and has remained unchanged since the agricultural revolution 10,000 years ago. Accumulating evidence suggests that the discrepancies between our Palaeolithic genome and ‘modern’ Western diet and lifestyle could play a significant role in the ongoing epidemics of obesity, hypertension, diabetes, atherosclerosis and other symptoms of metabolic syndrome (Kuneš & Zicha, 2009). This has been caused by the transition from wild and unprocessed food to a diet high in fat, sugar and salt. It has also been suggested that a sedentary lifestyle and overweight are major clinical and economic problems in modern societies. The worldwide epidemic of overweight is due to the imbalance between physical activity and dietary energy intake. A sedentary lifestyle, unhealthy diet and consequent overweight and obesity markedly increase the risk of subsequent cardiac events, such as non-fatal arrhythmia, myocardial infarction and sudden cardiac death. Regular physical activity (45–60 min per day) prevents unhealthy weight gain and obesity, whereas sedentary behaviours, such as watching television and/or working on a computer promote them. The best long-term results may be achieved when physical activity produces an energy expenditure of at least 200–500 kcal day−1. Regular moderate physical activity (mainly aerobic exercise), a healthy diet and avoidance of unhealthy weight gain are effective and safe ways to prevent and treat cardiovascular diseases. Moreover, there is plenty of evidence that exercise lowers blood pressure and has a beneficial influence on serum lipids. Recently, attention has been focused on the excessive accumulation of triglycerides (TGs) within the liver as a component of metabolic syndrome. It proves that fat accumulation in the liver is associated with several features of insulin resistance. Accumulation of TGs in hepatocytes is regulated by the integrated activities of cellular mechanisms that facilitate hepatic TG uptake, fatty acid synthesis and their esterification (input), which is balanced by hepatic fatty acid oxidation and TG export (output; den Boer et al. 2004). Steatosis occurs when input exceeds the capacity for output. Hepatic non-alcoholic steatosis is one of the most frequent liver diseases, occurring together with the plurimetabolic syndrome in overweight people. In this issue of Experimental Physiology, Crescenzo et al. (2014) clearly demonstrated that the short-term combined effects of dietary fat and fructose fed to adult rats, in proportions that mimic the Western diet, are similar to those induced by a high-fat diet alone. However, dual effects of this dietary regimen were apparent. Fructose supplementation did not worsen the deleterious effects of the high-fat diet on whole-body composition, but it worsened the plasma lipid profile by increasing circulating lipids, predominantly TGs and non-esterified fatty acids (NEFAs). These authors in their previous work (Crescenzo et al. 2008) have demonstrated that long-term feeding of a high-fat diet increases plasma NEFAs, which are associated with insulin resistance. Therefore, they hypothesized that increased plasma levels of NEFAs could contribute to hepatic insulin resistance during consumption of a high-fat diet. This hepatic insulin resistance is associated with steatosis, which means that the liver is less sensitive to the suppressive effects of insulin on hepatic glucose and TG production. Indeed, in their present paper (Crescenzo et al. 2014), the high-fat diet led to hepatic TG accumulation, and this was further increased by fructose supplementation. This observation indicates that the amount of liver TG content is not constant but can easily be modulated by nutritional conditions. The authors should be congratulated for this demonstration that short-term consumption of a Western diet, rich in saturated fat and sucrose, is more conducive to development of liver steatosis in adult rats than consumption of a high-fat diet alone. However, one should ask the question, what would be the situation in young animals in light of the fact that the number of overweight children is increasing? The answer is complicated because there is no information about developmental windows (critical developmental periods) regarding hepatic TG accumulation, hepatic insulin resistance and hepatic non-alcoholic steatosis. It is clear that the developing organism represents an ‘ideal terrain’ for the induction of many modifications, which could lead to the onset of certain diseases (Kuneš et al. 2012); therefore, detailed knowledge about the ontogenetic interactions of experimental animals with environmental factors might help us to understand the aetiology of many human diseases. Readers are invited to give their opinion on this article. To submit a comment, go to: http://ep.physoc.org/letters/submit/expphysiol;99/9/1180 None declared. The author is partially supported by grants AV0Z 50110509, 304/12/0259 (GA CR).
Read full abstract
Mar 1, 2019
Laura G Sanchez-Lozada + 8
Open Access
