Jan Oxholm Gordeladze

**Endocrinology**

Additional information is available at the end of the chapter Jan Oxholm Gordeladze

http://dx.doi.org/10.5772/67685 Additional information is available at the end of the chapter

**1. Introduction**

The comprehension of the genetics or "OMICS" (referring to a field of study in biology ending in -omics, such as genomics, proteomics or metabolomics), serving as a determinant in the development of obesity, has led to the identifications of genes closely associated with obesity-related diseases or ailments. Understanding of the etiology of adipogenesis has been of interest to the global community, i.e., obesity genetics, as well as its regulatory mechanisms, with transcription factors (TFs) being instrumental in the worldwide epidemics of overweight, with an increased risk for adiposity.

The identification of specific genes, sensitive to modulation by nutrients, as well as oxidative stress, inflammation mediators, endocrine factors/diseases, the turnover of lipids and carbohydrates (i.e., glucose and fructose, in particular), and insulin resistance has become a major focal point of the current obesity epidemic in various developed countries. "Epigenetics" is now construed as an important mechanism for the development of obesity, which may emanate from alterations in cellular chromatin structure without "touching" the DNA sequence itself, reaching from DNA methylation, histone modifications, and chromatin remodeling. The epigenetic modifications brought about by unhealthy "eating" affect nuclear and/or mitochondrial interplay, involving nuclear receptors like sirtuins, e.g., Sirt 1, serving as a single gene interacting with microRNAs, as well as transcription factors (TFs), e.g., p53, modulating cellular metabolism. These epigenetic players determine lipid turnover and energy expenditure, thereby inducing senescence followed by incomplete DNA repair. Epigenetic modifications in various socials communities are at present believed to induce "nonalcoholic fatty liver disease" (NAFLD), associated with excess fat transfer to white adipose tissues (WATs), thus leading to obesity in developed countries. The overt failure of a series of antiobese drugs advocates the use of so-called nutrigenomic diets, enabling a reverse of the senescence, which ensures an early and successful nutritional intervention combatting NAFLD, preceding a reduction in the number of severe adiposity, worldwide.

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© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, The enhancement in chronic diseases, such as obesity and diabetes (including early neurodegenerative diseases), is speculated to multiply by a factor of 5 by the year 2050, and will be linked to various organ diseases in the global population [1]. In overweight individuals, the increased adiposity is thought to be associated with epigenetic modifications, encompassing chromatin alterations induced by the environment and/or unhealthy diets. Genetic modifications inducing abnormal metabolic turnover in white adipose tissue (WAT) consolidate the defective nuclear mitochondrial interplay, leading to decrements in their energy expenditure.

Several hypotheses predicting the induction of obesity encompass the telomere-induction of cellular senescence associate a decline in telomeres with mitochondrial functioning [2, 3]. This phenomenon haunts humans in particular (in comparison to other mammals) and indicates that the human genes exhibit malfunctions in early childhood, like mitochondrial apoptosis associated with an enhanced probability of incurring nonalcoholic fatty hepatic disease (NAFLD), as well as degenerative, detrimental diseases [4, 5].

Furthermore, the theoretical aspects of age-related mutations and senescence [6, 7] have proven essential to describe the enhanced insulin resistance and the severity of weight gain and diabetes, which may be linked to xenobiotic ingestion in general [7, 8]. Adaptation model systems allude to theories of aging, postulating genetic alterations, like mutational patterns, which could be induced through excessive ingestion of dietary fats and sugars, which may lead to patterns of age-related mortality in general. Hereditary and/or evolutionary senescence mechanisms encompass known genetic approaches, which may yield information related to age-specific patterns of segregating genetic traits in various populations. Modern genetic analyses, such as DNA or RNA microarray analyses, are now available to aid in pinpointing age-related changes in the genetic "interplay." This has unraveled a solid identification of novel, age-dependent genetic pathways of metabolism, which are associated with disturbances in the steady state of the appearance of new mutations within single genes involved in diseases like NAFLD, as well as obesity worldwide [8].

Various lifestyles in a global population could decrease, or event prevent, senescence as well as mutations, associated with the telomere shortening theory, thus improving in adaptation of man to his environment. A single gene, like Sirt1 (Sirtuin-1), being involved in longevity, may govern the expression of a plethora of genes being of relevance to the triggering of organ diseases in obesity and diabetes. Sirt1 may be of relevance to both (a) the telomere hypothesis [2] and (b) the mitochondrial theories of aging [3, 4].

In different, closed habitats, the phenotypical transformation of a "versatile," i.e., beige adipocyte phenotype, to the traditional white, triglyceride-storing, adipocytes, has been linked to a poor glucose homeostasis. This is now associated to diabetes and hepatic malfunctioning and a defective Sirt1, leading to insulin resistance. Sirt1-mediated malfunctioning with concomitant loss of appetite control and NAFLD development in experimental animals seems to involve other genes, such as the obese (ob), leptin, fat, and agouti genes [8]. Sirt1 dysregulation and insulin resistance are linked to diabetes and encompass genes like the "mature-onset diabetes of the young genes," as well as others [9]. In obesity and diabetes, changes in Sirt1 expression is linked to the transcription factor p53, which enables the transformation the "normal" white adipose into an adipokine secreting tissue type, linked to NAFLD [6].
