A sideways glance: Lamarck strikes back? Fathers pass on to progeny characteristics they develop during their lives

摘要

The global prevalence of obesity is increasing across all age groups and in both sexes, contributing to the early emergence of insulin resistance usually followed by the development of type 2 diabetes (Kahn and Flier 2000; Reaven 1995). The pathology is determined by resistance to insulin action in multiple tissues, accompanied by failure of pancreatic β-cells to compensate the lack of response through increased insulin synthesis and secretion, a condition that leads to β-cell damage (Graham and Kahn 2007). Obesity in humans appears to be mostly related to complex interactions between genetic and environmental factors. Although diet affects the function of several somatic cell types playing a key role also in diseases like obesity and diabetes, it is widely accepted that none of the somatic cell effects can be transmitted to the next generation. The majority of environmental factors does not alter the animal’s DNA sequence, but rather promote alterations that can influence somatic cell metabolism, and therefore the health status of the individual exposed to them. In the current paradigm for disease etiology, either single-nucleotide polymorphisms (SNiPs) or chromosomal abnormalities can promote the onset of a disease; however, evidences are accumulating in the last years that also the environment is equally important in disease etiology.;Diet and food components are the prime environmental factors that affect the animal genome, transcriptome, proteome, and metabolome, and this life-long interaction largely defines the health or disease state of any individual. Most, if not all, nutrients have at least indirect effects on gene and protein expression and therefore on metabolism.;The genome is evolutionarily and chemically rather stable. The ability of environmental factors to influence or promote disease onset and progression does not generally involve induction of DNA mutations, but acts through the regulation of genome activity, influencing disease etiology at different stages of development. Such altered metabolic programs can in turn promote abnormal physiology and disease onset at later developmental stages through epigenetic mechanisms.;The past few years have witnessed an important expansion in the understanding of inheritance, in parallel with the increasing variety of epigenetically inherited traits that have been described. Mechanisms thus exist that could allow organisms to tell their progeny about prevailing environmental conditions like for example the repeated exposure to a moderately toxic environment. Whether or not organisms can inherit characters induced by ancestral environments has serious implications. This type of inheritance is called “Lamarckian” inheritance after JB Lamarck who believed in the inheritance of acquired traits.;The term “epigenetics” was coined by Conrad Waddington in the 1940s to integrate the concepts of embryological growth and differentiation (epigenesis) with genetics and has evolved since then with the increased understanding of genes and genomes. Epigenetics focuses on molecular elements that can influence chromatin structure, irrespective of the DNA sequence. At present, the best definitions of epigenetics seem to be: “molecular factors and processes around DNA that are mitotically stable and regulate genome activity independently from DNA sequence” or “the study of mitotically and/or meiotically heritable changes in gene expression or cellular phenotype, which occur without changes to the underlying DNA sequence.” The first epigenetic molecular factor, identified in the 1970s, was DNA methylation. In the mid-1990s, DNA methylation was followed by histone modification, together with the appreciation of the role of chromatin structure in genome regulation. Then, around the year 2000, non-coding RNA was discovered, and finally in 2005, the first whole epigenome was analyzed. New epigenetic processes have been described in the past few years, whose function is not yet completely unders