Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring

  title={Chronic high-fat diet in fathers programs $\beta$-cell dysfunction in female rat offspring},
  author={Sheau-Fang Ng and Ruby C Y Lin and David Ross Laybutt and Romain Barr{\`e}s and Julie A Owens and Margaret J. Morris},
The global prevalence of obesity is increasing across most ages in both sexes. This is contributing to the early emergence of type 2 diabetes and its related epidemic. Having either parent obese is an independent risk factor for childhood obesity. Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are well established, the extent of any contribution of obese fathers is unclear, particularly the role of non-genetic factors in the causal… 

Paternal long‐term exercise programs offspring for low energy expenditure and increased risk for obesity in mice

  • A. MurashovE. Pak P. Neufer
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2016
It is suggested that paternal exercise produces offspring with a thrifty phenotype, potentially via miRNA‐induced modification of sperm, providing a potential mechanism for the transgenerational inheritance.

Effects of paternal obesity on growth and adiposity of male rat offspring.

It is proposed that the reduced GH secretion at 8 wk of age altered the growth of male offspring from HFD-F0, resulting in smaller animals from 9 wk to 6 mo of age, potentially increasing their metabolic risk.

Intergenerational Influence of Paternal Obesity on Metabolic and Reproductive Health Parameters of the Offspring: Male-Preferential Impact and Involvement of Kiss1-Mediated Pathways

It is suggested that HFD-induced metabolic and reproductive disturbances are exacerbated by paternal obesity preferentially in males, whereas kisspeptin effects are affected in both sexes.

Paternal obesity induces metabolic and sperm disturbances in male offspring that are exacerbated by their exposure to an “obesogenic” diet

It is indicated that metabolic and fertility disturbances in male offspring sired by HFD fathers are exacerbated by a “second‐hit” of exposure to the same obesogenic environment postnatally, relevant to the current worldwide obesity epidemic.

Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring

Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD.

Programming of Obesity and Comorbidities in the Progeny: Lessons from a Model of Diet-Induced Obese Parents

Male and female offspring of a mother and father that received a HF diet demonstrated the effects of paternal obesity most prominently in adult life, alterations in glucose metabolism, increase in components of lipogenesis and liver steatosis.

Maternal Western diet increases adiposity even in male offspring of obesity-resistant rat dams: early endocrine risk markers.

Maternal Western diet covertly programmed increased adiposity in childhood and adulthood, disrupted relations of energy regulatory hormones with body fat, and decreased energy expenditure in offspring of lean, genetically obesity-resistant mothers.

Paternal Obesity, Interventions, and Mechanistic Pathways to Impaired Health in Offspring

Paternal overweight/obesity induces paternal programming of offspring phenotypes likely mediated through genetic and epigenetic changes in spermatozoa, and these programmed changes to offspring health appear to be partially restored via diet/exercise interventions in obese fathers preconception.

Paternal Exercise Improves Glucose Metabolism in Adult Offspring

Voluntary exercise training of male mice results in pronounced improvements in the metabolic health of adult male and female offspring, and provides the first in-depth analysis of small RNAs in sperm from exercise-trained males, revealing a marked change in the levels of multiple smallRNAs with the potential to alter phenotypes in the next generation.



Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice.

These studies provide evidence that the heritability of body length and glucose homeostasis are modulated by maternal diet across multiple generations, providing a mechanism where length can increase rapidly in concert with caloric availability.

Intergenerational Transmission of Glucose Intolerance and Obesity by In Utero Undernutrition in Mice

Maternal undernutrition during pregnancy (F0) programs reduced birth weight, IGT, and obesity in both first- and second-generation offspring.

Early life influences on obesity risk: maternal overnutrition and programming of obesity

  • M. Morris
  • Biology
    Expert review of endocrinology & metabolism
  • 2009
This review summarizes recent evidence of the impact of maternal obesity on subsequent obesity risk, paying particular attention to the hypothalamic regulation of appetite and markers of metabolic control.

Diet-Induced Obesity in Male Mice Is Associated with Reduced Fertility and Potentiation of Acrylamide-Induced Reproductive Toxicity1

It is demonstrated that diet-induced obesity in mice caused a significant reduction in male fertility and exacerbated AA-induced reproductive toxicity and germ cell mutagenicity.

Undernutrition during suckling in rats elevates plasma adiponectin and its receptor in skeletal muscle regardless of diet composition: a protective effect?

This study demonstrates the important role of early nutrition on body weight and metabolism, suggesting early undernourishment enhances insulin sensitivity and fatty-acid oxidation.

Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific.

The studies show that LP dietary insult in early, middle, or late gestation, all result in a relative deficiency of beta cells following birth, due to a failure to develop larger islets, but that females were particularly susceptible in mid-gestation and males in late gestation.

Genetic and Environmental Influences on Human Cord Blood Leptin Concentration

Cord blood leptin concentration is elevated in the presence of a family history of obesity on the paternal side, but not on the maternal side, and may help clarify the role of leptin in parental contributions to human obesity.

Childhood obesity: are genetic differences involved?

  • C. Bouchard
  • Biology, Medicine
    The American journal of clinical nutrition
  • 2009
This brief review focuses on the genetic contribution to childhood obesity, and suggests that the prevalence of childhood obesity is increasing across generations as a result of positive assortative mating with obese husbands and wives contributing more obese offspring than normal-weight parents.

Parental diabetes and birth weight of offspring: intergenerational cohort study

This large cohort study of British births in 1958 was used to evaluate whether a father's non-insulin dependent diabetes or a mother's diabetes starting after childbirth is associated with the birth weight of their offspring.