Exercise in obese fathers restores son’s metabolic health via changes to pancreatic morphology and function — ASN Events
  1. Schedule
  2. Session 5.2: Paternal impacts on Development
  3. Exercise in obese fathers restores son’s metabolic health via changes to pancreatic morphology and function

Exercise in obese fathers restores son’s metabolic health via changes to pancreatic morphology and function (#36)

Nicole McPherson 1 2 , Julie A Owens 1 , Tod Fullston 1 , Michelle Lane 1 3
  1. School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology, Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia
  2. Fremasons Center for Mens Health, University of Adelaide, Adelaide, SA, Australia
  3. Repromed, Dulwich, SA, Australia

Recent studies have shown that male obesity can program obesity, metabolic syndrome and subfertility in subsequent offspring. Currently one study has shown that this paternal programming maybe reversible with lifestyle interventions to obese founders restoring sperm function in male offspring. Whether similar exercise interventions to fathers can additionally restore metabolic health of their sons is unknown.


C57BL6 male mice (n=30) were fed either a control diet (CD-6%-fat) or a high fat diet (HFD-21%-fat) for 10 weeks before HFD mice were allocated to either exercise (HE) or a continued HFD (HH) for a further 8 weeks. Males were mated with CD females and male offspring assessed. At 8/17weeks of age, male offspring (n=10 per group) were assessed for glucose tolerance (GTT) and insulin tolerance (ITT). Pancreas (n=6 per group) was collected post-mortem (18weeks) and islet cell morphology and microRNAs abundance assessed.


Exercise intervention in founders (HE) restored male offspring insulin tolerance during an ITT at both 8 (+16%) and 17 (+23%) weeks compared with HH offspring (p<0.05) and glucose tolerance during a GTT at 17 weeks (+10%, p<0.05), suggesting improved pancreatic islet cell function. Morphological assessment of pancreas showed increased islet cell density (+18%) and large islet cell size (+11%) in HE offspring compared with HH offspring (p>0.05) and comparable to CC offspring, with no differences in pancreatic mass. Further, key microRNAs targeting genes implicated in insulin secretion and glucose regulation, were altered in HH compared to CC offspring (p<0.05) and restored in HE offspring (p<0.05); of note, these microRNAs are also dysregulated in HH founder sperm (mir-181a-5p, mir-153-3p, mir-128-3p and mir-142-5p).


This is the first study to show that male offspring metabolic health and key regulator pathways (microRNAs) can be improved by simple exercise interventions to father. This suggests that lifestyle interventions in impaired paternal health could have significant implications for the metabolic programming of the next generation.