Environmental and Nutritional Effects Regulating Adipose Tissue Function and Metabolism Across Generations

Abstract

The unabated rise in obesity prevalence during the last 40 years has spurred substantial interest in understanding the reasons for this epidemic. Studies in mice and humans have demonstrated that obesity is a highly heritable disease; however genetic variations within specific populations have so far not been able to explain this phenomenon to its full extent. Recent work has demonstrated that environmental cues can be sensed by an organism to elicit lasting changes, which in turn can affect systemic energy metabolism by different epigenetic mechanisms such as changes in small noncoding RNA expression, DNA methylation patterns, as well as histone modifications. These changes can directly modulate cellular function in response to environmental cues, however research during the last decade has demonstrated that some of these modifications might be transmitted to subsequent generations, thus modulating energy metabolism of the progeny in an inter- as well as transgenerational manner. In this context, adipose tissue has become a focus of research due to its plasticity, which allows the formation of energy storing (white) as well as energy wasting (brown/brite/beige) cells within the same depot. In this Review, the effects of environmental induced obesity with a particular focus on adipose tissue are discussed.

Keywords: adipose tissue; diabetes; epigenetics; obesity; transgenerational epigenetic inheritance.

Figure 1

Energy balance: the main determinant of body weight is controlled by multiple factors, which regulate energy accumulation and expenditure.

Figure 2

Body weight is highly heritable,24, 25 however DNA sequence variations identified so far, account for only a small percentage of the observed heritability. This mismatch might potentially be due to epigenetic regulation.

Figure 3

Adipose tissue distribution in humans and mice. Brown adipose tissue composed of either brown or brite/beige adipocytes in humans is mainly localized in cervical, supraclavicular, axillary, paraspinal, and perirenal depots. In mice, brown adipocytes are located in the interscapular depot while brite/beige adipocytes are found interspersed in different depots.

Figure 4

Environmental cues could be transmitted cross generations. In the case of in utero expose, F1 and F2 transmissions are classified as intergenerational epigenetic inheritance, F3 and further generations are transgenerational epigenetic inheritance. In the case of paternal exposure, F1 is classified as inter‐, while F2 and beyond as transgenerational epigenetic inheritance. DNA methylation, histone modification and s‐ and lncRNAs are involved in the epigenetic transmission.