Developmental Adipogenesis and Later-Life Cardiometabolic Risk in Offspring Exposed to Dams with Metabolic Dysfunction
| dc.contributor.advisor | Thompson, Jennifer A. | |
| dc.contributor.author | Mikolajczak, Anna | |
| dc.contributor.committeemember | Huang, Carol T. L. | |
| dc.contributor.committeemember | Slater, Donna M. | |
| dc.date | 2020-11 | |
| dc.date.accessioned | 2020-09-29T18:55:03Z | |
| dc.date.available | 2020-09-29T18:55:03Z | |
| dc.date.issued | 2020-09-25 | |
| dc.description.abstract | Intrauterine exposure to maternal obesity and diabetes is linked to the development of obesity and other cardiovascular disease (CVD) risk factors in the offspring. The hypothesis for this study is that impaired subcutaneous adipose tissue (SAT) expandability underlies the development of CVD risk factors in offspring born to metabolically compromised pregnancies. Female mice heterozygous for leptin receptor deficiency (Hetdb) were used as a model of maternal metabolic dysfunction. Wild type (Wt) offspring from Wt or Hetdb pregnancies were examined as either neonates or adults fed a control diet (CD) or a high fat/fructose (HFF) diet. Aim 1 of my study was to determine the effect of a metabolically compromised pregnancy on developmental adipogenesis. Measurement of whole-body fat mass and plasma resistin revealed that fat accumulation was heightened in neonates born to the Hetdb vs. Wt dams. Cell size distribution data confirmed the presence of larger-sized adipocytes in the inguinal SAT (iSAT) of neonates from the Hetdb pregnancy. Oil Red O staining, Western Blot and qPCR demonstrated a higher adipogenic potential in progenitor cells isolated from neonates born to the Hetdb pregnancy. Aim 2 of my study was to determine if SAT dysfunction is associated with CVD risk factors in offspring born to dams with metabolic dysfunction. Offspring exposed to Hetdb pregnancy had a predisposition for developing risk factors associated with CVD in adulthood. Higher circulating free fatty acids were accompanied by impairment of insulin-stimulated inhibition of lipolysis, indicating the manifestation of adipose tissue dysfunction. The differences in distribution of adipocyte diameter observed shortly after birth persisted into adulthood in CD-fed offspring, suggesting a predisposition to hypertrophic dysfunction, the cause of insulin resistance in adipocytes. In vitro differentiation studies in isolated adipocyte progenitors revealed that the intrinsic differentiation capacity of adipocyte-derived stem cells was not the mechanism responsible for impaired SAT function. In conclusion, intrauterine exposure to metabolic dysfunction leads to accelerated developmental adipogenesis and a later-life perturbation in lipid handling. Therefore, CVD risk may arise from SAT dysfunction programmed during the critical perinatal window of SAT development. Keywords: Fetal programming, adipogenesis, cardiovascular disease | en_US |
| dc.identifier.citation | Mikolajczak, A. (2020). Developmental Adipogenesis and Later-Life Cardiometabolic Risk in Offspring Exposed to Dams with Metabolic Dysfunction (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/38274 | |
| dc.identifier.uri | http://hdl.handle.net/1880/112615 | |
| dc.publisher.faculty | Cumming School of Medicine | en_US |
| dc.publisher.institution | University of Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | en_US |
| dc.subject | Fetal programming | en_US |
| dc.subject | Adipogenesis | en_US |
| dc.subject | Cardiovascular disease | en_US |
| dc.subject.classification | Human Development | en_US |
| dc.subject.classification | Nutrition | en_US |
| dc.subject.classification | Obstetrics and Gynecology | en_US |
| dc.title | Developmental Adipogenesis and Later-Life Cardiometabolic Risk in Offspring Exposed to Dams with Metabolic Dysfunction | en_US |
| dc.type | master thesis | en_US |
| thesis.degree.discipline | Medicine – Cardiovascular/Respiratory Science | en_US |
| thesis.degree.grantor | University of Calgary | en_US |
| thesis.degree.name | Master of Science (MSc) | en_US |
| ucalgary.item.requestcopy | true | en_US |