Maternal Socs3 knockdown attenuates postnatal obesity caused by an early life environment of maternal obesity and intrauterine overnutrition in progeny mice

SUMMARYHuman cytomegalovirus (CMV) is a common herpesvirus establishing lifelong persisting infection, which has been implicated in immunosenescence and mortality in the elderly. Little is known about how and when susceptibility to CMV infection is determined. We measured CMV seroprevalence in two genetically informative cohorts. From the Leiden Longevity Study (LLS) we selected long-lived sib-pairs (n=844) and their middle-aged offspring and the offspring's partners (n=1452). From the Longitudinal Study of Aging Danish Twins (LSADT) 604 (302 pairs) same-sex monozygotic (MZ) and dizygotic (DZ) twins aged 73–94 years were included (n=302 pairs). Offspring of the long-lived LLS participants had significantly lower seroprevalence of CMV compared to their partners (offspring: 42%vs. partners: 51%,P=0·003). Of 372 offspring living with a CMV-positive partner, only 58% were infected. The corresponding number for partners was 71% (P<0·001). In the LSADT, MZ and DZ twins had high and similar CMV-positive concordance rates (MZ: 90%vs. DZ: 88%,P=0·51) suggesting that shared family environment accounts for the similarity within twin pairs. Our findings suggest that susceptibility to CMV infection – even under continuous within-partnership exposure – appears to be more strongly influenced by early-life environment than by genetic factors and adult environment.

Download Full-text

Epigenetics and DOHaD: from basics to birth and beyond

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174417000733 ◽

2017 ◽

Vol 8 (5) ◽

pp. 513-519 ◽

Cited By ~ 74

Author(s):

T. Bianco-Miotto ◽

J. M. Craig ◽

Y. P. Gasser ◽

S. J. van Dijk ◽

S. E. Ozanne

Keyword(s):

Dna Methylation ◽

Chronic Disease ◽

Chronic Diseases ◽

Early Life ◽

Later Life ◽

Metabolic Health ◽

Number Of Children ◽

Early Life Environment ◽

Increased Risk ◽

Early Life Exposures

Developmental origins of health and disease (DOHaD) is the study of how the early life environment can impact the risk of chronic diseases from childhood to adulthood and the mechanisms involved. Epigenetic modifications such as DNA methylation, histone modifications and non-coding RNAs are involved in mediating how early life environment impacts later health. This review is a summary of the Epigenetics and DOHaD workshop held at the 2016 DOHaD Society of Australia and New Zealand Conference. Our extensive knowledge of how the early life environment impacts later risk for chronic disease would not have been possible without animal models. In this review we highlight some animal model examples that demonstrate how an adverse early life exposure results in epigenetic and gene expression changes that may contribute to increased risk of chronic disease later in life. Type 2 diabetes and cardiovascular disease are chronic diseases with an increasing incidence due to the increased number of children and adults that are obese. Epigenetic changes such as DNA methylation have been shown to be associated with metabolic health measures and potentially predict future metabolic health status. Although more difficult to elucidate in humans, recent studies suggest that DNA methylation may be one of the epigenetic mechanisms that mediates the effects of early life exposures on later life risk of obesity and obesity related diseases. Finally, we discuss the role of the microbiome and how it is a new player in developmental programming and mediating early life exposures on later risk of chronic disease.

Download Full-text

Maternal Obesity and Developmental Programming of Metabolic Disorders in Offspring: Evidence from Animal Models

Experimental Diabetes Research ◽

10.1155/2011/592408 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 96

Author(s):

M. Li ◽

D. M. Sloboda ◽

M. H. Vickers

Keyword(s):

Animal Models ◽

Early Life ◽

Metabolic Disorders ◽

Maternal Obesity ◽

Maternal Weight ◽

Critical Window ◽

Obesity Epidemic ◽

Obesity And Overweight ◽

Increased Risk ◽

Maternal Overnutrition

The incidence of obesity and overweight has reached epidemic proportions in the developed world as well as in those countries transitioning to first world economies, and this represents a major global health problem. Concern is rising over the rapid increases in childhood obesity and metabolic disease that will translate into later adult obesity. Although an obesogenic nutritional environment and increasingly sedentary lifestyle contribute to our risk of developing obesity, a growing body of evidence links early life nutritional adversity to the development of long-term metabolic disorders. In particular, the increasing prevalence of maternal obesity and excess maternal weight gain has been associated with a heightened risk of obesity development in offspring in addition to an increased risk of pregnancy-related complications. The mechanisms that link maternal obesity to obesity in offspring and the level of gene-environment interactions are not well understood, but the early life environment may represent a critical window for which intervention strategies could be developed to curb the current obesity epidemic. This paper will discuss the various animal models of maternal overnutrition and their importance in our understanding of the mechanisms underlying altered obesity risk in offspring.

Download Full-text