Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2023

The impact of a high-fat high-sugar diet on gastric vagal afferent mechanosensitivity in pregnant dams and their offspring (99111)

Georgia Clarke 1 2 3 , Hui Li 1 3 , Stephanie O’Hara 2 3 4 , Kelly Gembu 2 3 4 , Lisa M. Nicholas 2 3 4 , Sharon R. Ladyman 5 , Kathryn L. Gatford 1 2 3 , Amanda J. Page 1 3
  1. Lifelong Health Theme, South Australian Health and Medical Research Institue, Adelaide, South Australia, Australia
  2. Robinson Research Institute, University of Adelaide, adelaide, South Australia, Australia
  3. Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
  4. Adelaide Centre for Epigenetics, University of Adelaide, Adelaide, Australia, Adelaide
  5. Centre for Neuroendocrinlogy and Department of Anatomy, University of Otago, Dunedin, New Zealand

Background: Increased food intake during pregnancy is essential for progeny health. However, over-nutrition during pregnancy negatively impacts progeny development and long-term health. Gastric vagal afferents (GVAs) sense food-related mechanical stimuli, including stomach distension, and signal to the brain, ultimately terminating a meal. Pregnancy and diet-induced obesity are independently associated with dampened GVA mechanosensitivity and increased food intake. It is unknown how GVA signalling across pregnancy is impacted by diet-induced obesity or whether maternal obesity impacts GVA signalling in the progeny.


Aims: To assess GVA mechanosensitivity: 1) during pregnancy in mice fed standard laboratory diet (SLD) or high-fat, high-sugar diet (HFHSD); and 2) in the progeny of mice fed a SLD or HFHSD before and throughout pregnancy and lactation.

Methods: For study 1, female GLU-Venus mice (3-weeks-old) were fed a SLD or HFHSD for 12-weeks, then half of each group were mated to generate late-pregnant or non-pregnant groups. At gestational day 17.5 or age-matched equivalent for the non-pregnant groups, the mice were humanely killed. For study 2, SLD-fed offspring (8-weeks-old) of dams fed a SLD or HFHSD were humanely killed. Tissue from both studies were collected at 0700 hr for in vitro single fibre GVA preparation.

Results: The response of tension-sensitive GVAs to stretch was attenuated by pregnancy in SLD-fed mice (P<0.01) and was lower in HFHSD-fed than SLD-fed non-pregnant mice (P<0.001). However, GVA responses to stretch were similar in HFHS-fed pregnant and non-pregnant mice. In progeny, the response of tension-sensitive GVAs to stretch was attenuated by maternal HFHSD in males (P<0.001), but maternal diet did not affect GVA responses in females.

Conclusion: A HFHSD attenuates GVA satiety signalling and there is no further adaptations in GVA satiety signalling during pregnancy. Maternal HFHSD also down-regulates GVA satiety signalling in male but not female progeny, possibly contributing to intergenerational transmission of obesity.