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

Abstract

Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our previous work using a rodent model of diet-induced paternal obesity showed that female offspring from high-fat diet (HFD)-fed fathers develop glucose intolerance due to impairment of pancreatic insulin secretion. Here, we focused on the health outcomes of male offspring from HFD-fed fathers. Male Sprague-Dawley rats (3 wk old) were fed control (CD-F0) or HFD (HFD-F0) for 12 wk before mating with control-fed females. Male offspring were fed control diets for up to 8 wk or 6 mo. Although male offspring from HFD-F0 did not develop any obvious glucose metabolism defects in this study, surprisingly, a growth deficit phenotype was observed from birth to 6 mo of age. Male offspring from HFD-F0 had reduced birth weight compared with CD-F0, followed by reduced postweaning growth from 9 wk of age. This resulted in 10% reduction in body weight at 6 mo with significantly smaller fat pads and skeletal muscles. Reduced circulating levels of growth hormone (GH) and IGF-I were detected at 8 wk and 6 mo, respectively. Expression of adipogenesis markers was decreased in adipose tissue of HFD-F0 offspring at 8 wk and 6 mo, and expression of growth markers was decreased in muscle of HFD-F0 offspring at 8 wk. We propose 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. Furthermore, increased muscle triglyceride content and expression of lipogenic genes were observed in HFD-F0 offspring, potentially increasing their metabolic risk.

Four weeks of exercise early in life reprograms adult skeletal muscle insulin resistance caused by a paternal high‐fat diet

“…However, we found that body weight was lower in female adult offspring fathered by rats fed with HFD, which was also reported in male offspring (Lecomte et al . ). Ng et al .…”

Parental adiposity differentially associates with newborn body composition

“…The study, led by Ng et al, focused on females and found paternal obesity to induce sustained pancreatic β‐cell dysfunction in the offspring without altering growth or adiposity. More recently, and using a similar murine model, Lecomte et al reported birthweight and growth trajectories of male offspring are dramatically affected by paternal obesity, with lower birthweight, stunted growth and decreased adiposity occurring in association with low levels of GH and IGF1 factor.…”

“…Undeniably, the experiences of the developing embryo/foetus are primarily those of the mother; therefore, it is maternal contributions to programming of offspring health that have captivated research efforts. In the United States where ~50% of babies are being born to women with either overweight or obesity, a clear link has been established between maternal obesity at conception and offspring's obesity and cardiometabolic risks across the lifespan. In recent years, however, studies have pointed out that paternal obesity is also contributing to the programming of offspring phenotype, but the results from some of these studies are conflicting.…”

“…For instance, Chen et al reported that foetal growth is positively associated with paternal body mass index (BMI) in male, but not female babies, while another study found that obesity in fathers increases the risk of intrauterine growth restriction, a known risk factor for cardiovascular disease later in life. Murine models of paternal obesity also show different results, with studies reporting that offspring weight and/or adiposity are either unaffected or decreased by paternal obesity. In the latter case, programming of the growth hormone (GH) insulin‐like growth factor (IGF) axis has been proposed as a potential mechanism.…”

“…Murine models of paternal obesity also show different results, with studies reporting that offspring weight and/or adiposity are either unaffected or decreased by paternal obesity. In the latter case, programming of the growth hormone (GH) insulin‐like growth factor (IGF) axis has been proposed as a potential mechanism.…”