Nutrition and its role in epigenetic inheritance of obesity and diabetes across generations

Abstract

Nutritional constraints including not only caloric restriction or protein deficiency, but also energy-dense diets affect metabolic health and frequently lead to obesity and insulin resistance, as well as glucose intolerance and type 2 diabetes. The effects of these environmental factors are often mediated via epigenetic modifiers that target the expression of metabolic genes. More recently, it was discovered that such parentally acquired metabolic changes can alter the metabolic health of the filial and grand-filial generations. In mammals, this epigenetic inheritance can either follow an intergenerational or transgenerational mode of inheritance. In the case of intergenerational inheritance, epimutations established in gametes persist through the first round of epigenetic reprogramming occurring during preimplantation development. For transgenerational inheritance, epimutations persist additionally throughout the reprogramming that occurs during germ cell development later in embryogenesis. Differentially expressed transcripts, genomic cytosine methylations, and several chemical modifications of histones are prime candidates for tangible marks which may serve as epimutations in inter-and transgenerational inheritance and which are currently being investigated experimentally. We review, here, the current literature in support of epigenetic inheritance of metabolic traits caused by nutritional constraints and potential mechanisms in man and in rodent model systems.

tRNA Biology in the Pathogenesis of Diabetes: Role of Genetic and Environmental Factors

“…Another piece of evidence supporting the role of environmentally altered tRNAs metabolism in obesity and diabetes is the implication of tRNA fragments in the intergenerational inheritance of metabolic traits (Figure 4). Epidemiological and preclinical data suggest that paternal protein-poor or caloric-restricted diets as well as energy-dense diets may influence paternal heredity, predisposing offspring to obesity, insulin resistance, and T2D [197][198][199][200]. Female rats born from HFD-fed fathers have impaired glucose tolerance and reduced insulin secretion as a consequence of pancreatic β-cell dysfunction [201], while premating fasting of male mice was shown to influence the offspring's glycemia [202].…”

Emerging Classes of Small Non-Coding RNAs With Potential Implications in Diabetes and Associated Metabolic Disorders

“…Intergenerational inheritance of metabolic disorders and b-cell dysfunction are established (142)(143)(144). In recent years, paternal metabolic challenges were shown to be correlated with alterations in sperm tRFs in humans, mice, and rats (111,120,145,146).…”

Exploring the Role of Maternal Nutritional Epigenetics in Congenital Heart Disease

“…In mammals, epigenetic inheritance is either intergenerational or transgenerational ( 52 ). Intergenerational inheritance will pass on the epimutations established in gametes that survive the epigenetic reprogramming events during the preimplantation stage.…”

“…Intergenerational inheritance will pass on the epimutations established in gametes that survive the epigenetic reprogramming events during the preimplantation stage. If epimutations persist throughout the additional reprogramming during germ cell development in the later part of embryonic growth, it is referred to as transgenerational inheritance ( 52 ). The transgenerational epigenetic effect of nutrition has been explored by various researchers.…”