Obesogenic Diet Drives Epigenetic Predisposition To Metabolic Disorders

Obesogenic Diet Drives Epigenetic Predisposition To Metabolic Disorders

An obesogenic diet may cause inheritable epigenetic changes. Learn more about the possible impact of an obesogenic diet on future generations.

 

In this article:

  1. Can a Father’s Obesogenic Diet Predispose Offspring to Metabolic Disorders?
  2. Obesogenic Diet Propels an Epigenetic Predisposition to Metabolic Disorders
  3. Transgenerational and Intergenerational Nongenetic Inheritance
  4. Epigenetics and Environmental Influences
  5. Consequences for Multiple Generations Exposed to an Obesogenic Diet

Obesogenic Diet | Rethinking Epigenetic Inheritance

 

Can a Father’s Obesogenic Diet Predispose Offspring to Metabolic Disorders? 

The possibility to pass down individual epigenetic changes to future generations has made us rethink what inheritance is. Nongenetic inheritance is becoming common in current epigenetic research. 

Recent studies have begun to recognize the mechanisms underlying the acquisition of phenotypic traits induced by specific environmental cues in the parents of individuals. 

Paternal contribution to birth weight induced by an unhealthy diet can affect the metabolism of the offspring. A new study found significant evidence that paternal obesity affects the metabolic health of their progeny [5]. 

Nongenetic inheritance of received phenotypes is where changes caused by environmental cues induced within the parents, grandparents, and so on, can be transmitted to their offspring [3]. 

Epigenetic factors in gametes play an important role in the intergenerational transmission of obesity and type 2 diabetes. This has sparked interest in whether transgenerational inheritance also occurs via gametes [2, 4].

 Environmental cues can potentially modify molecular-heritable information carried by the sperm. They are demonstrating that environmentally induced epigenetic modifications are not erased through the process of epigenetic reprogramming. 

This causes the way the paternal epigenome is expressed and passed onto their offspring [5]. The evidence suggests that the father’s unhealthy diet negatively affected the metabolic health of their multigenerational descendants.

 

Obesogenic Diet Propels an Epigenetic Predisposition to Metabolic Disorders

ast food snacks and cola drink on wooden table | Obesogenic Diet Propels an Epigenetic Predisposition to Metabolic Disorders | Obesogenic Diet Drives Epigenetic Predisposition To Metabolic Disorders | Obesogenic Diet Drives Epigenetic Predisposition To Metabolic Disorders

Obesity is a growing public health concern that is responsible for 4 million deaths a year globally. The epigenetic inheritance of acquired metabolic disorders may contribute to the current obesity and diabetes pandemic [4]. 

The Western diet (WD) is a diet consisting of high-fat and high-sugar junk foods. Most studies only looked at the single generational effects of the WD on the father and his offspring’s phenotype. This new study’s findings revealed that maintaining a WD for several generations promotes the accumulation of epigenetic alterations in somatic and germline cells [5].

This study is all about the paternal maintenance of the WD’s part in multiple generations’ metabolic phenotype. Examining the function of nongenetic inheritance and the environment’s role in obese individuals has uncovered that paternal contribution to birth weight is induced by an unbalanced diet. 

This paternal contribution can affect the metabolism and metabolic pathologies of the offspring. One obese-associated pathology, hepatic steatosis, was identified and that it increased in severity with the ensuing generations that consumed the WD. 

The appearance of the obese-phenotype after multigenerational WD feeding indicates that obesogenic sensitivity is elevated by multiple generations of exposure [5].

 

Transgenerational and Intergenerational Nongenetic Inheritance

In the study, they maintained a paternal WD feeding in five consecutive generations of mice, which induced a gradual enhancement of fat mass and metabolic diseases over the course of the multiple generations being observed [5]. 

The researchers compared the metabolic parameters across the multiple generations of WD males.

The progenies of fathers with several WD-fed ancestors were consistently overweight for the following 4 generations, even if their father did not get fed the WD. Meaning the epigenetic inheritance of an obese phenotype is transgenerational (figure 1). Notably, males who were third and fourth generation-descendants of obese WD-fed males ended up not becoming overweight themselves.

So the obese phenotype triggered by environmental exposure of the WD in preceding paternal generations was not the only influencing factor on the mice’s phenotypes. Excluding the individual’s own diet is not painting the entire picture; this data supports that it is both the ancestral and individual diet that causes a severe metabolic effect [5].

 

Transgenerational and Intergenerational Nongenetic Inheritance

Epigenetic alterations associated with aging have been found to accelerate as a result of a high-fat diet, indicating that environmental factors play a significant part in the aging of an individual. 

Unlike genetic inheritance, environmentally-triggered epigenetic alterations are reversible, but environmental changes to the epigenome can persist over several generations [5]. This helps explain why some people seem to have a predisposition to obesity. 

Epigenetic information can be inherited through the germline, and sperm represents a plausible transgenerational carrier of environmental information [1]. Sperm RNA is the vector for paternal-intergenerational epigenetic inheritance of environmentally induced metabolic pathologies [3]. 

Environmentally induced epigenetic modifications in germlines contribute to the environmental adaptation of that species. This shows the importance of assessing each epigenetic vector for inheritance and how they will interact together to regulate the epigenome of the embryo during development. 

 

Consequences for Multiple Generations Exposed to an Obesogenic Diet

This study indicated that multigenerational exposure forced stress-induced phenotypes, which affected the metabolic state of the subsequent generations that were never directly exposed to a WD. The study showed that sperm RNAs are vectors of intergenerational inheritance but aren’t really good for the transgenerational inheritance of diet-induced metabolic alterations [5].

RNAs as vectors for epigenetic inheritance only works within the span of one generation from father to its progeny and isn’t capable of transcending multiple generations unless multiple generations have consecutively been exposed to the WD. But, as mentioned, the generations that were exposed back-to-back to the WD had the most severe overweight phenotype and metabolic disorders [5].

Ancestral exposure to the WD influenced the magnitude of the progeny’s weight, but it is not the only thing to think about when addressing severe obesity. 

Knowing that environmentally induced epigenetic modifications in germlines contribute to the offspring’s phenotypic traits is an essential factor when considering the health consequences of obesity and its comorbidities. 

Hopefully, by uncovering the mechanisms that drive epigenetic inheritance of phenotypes can help find therapies and preventative treatments for individuals with a predisposition to metabolic disorders.

 

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