title: Effect of GLP-1 Receptor Activation on Offspring Kidney Health in a Rat Model of Maternal Obesity.
abstract: Maternal obesity is associated with an increased risk of chronic disease in offspring, including type 2 diabetes (T2D). Exendin-4 (Exd-4) activates the glucagon like peptide-1 (GLP-1) receptor thereby decreasing serum glucose levels and body weight. In addition, Exd-4 has been shown to reduce renal and cardiac complications in experimental models of T2D. We hypothesized that treatment with Exd-4 would ameliorate the detrimental effects of maternal and diet-induced obesity on renal characteristics in offspring. Female Sprague-Dawley rats were fed either normal or high-fat diet (HFD) for 6 weeks prior to pregnancy, during pregnancy and lactation, and their offspring were weaned to normal or HFD. The offspring were randomized to Exd-4 or placebo from weaning and their kidneys harvested at Week 9. We found that the kidneys of offspring from obese mothers, regardless of postnatal diet, had significantly increased markers of inflammation, oxidative stress and fibrosis. Exd-4 ameliorated the negative renal effects of maternal obesity and in particular, reduced renal inflammation, oxidative stress and fibrosis. In conclusion, maternal obesity has persisting effects on renal structure in the offspring. GLP-1 analogues are potentially useful for protecting against the deleterious effects of maternal obesity on renal physiology in offspring.
authors.affiliation: Department of Medicine, Kolling Institute, University of Sydney, NSW, Australia.|Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Glastras
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, NSW, Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Rachel T
authors.initials: RT
authors.lastname: McGrath
authors.affiliation: Department of Medicine, Kolling Institute, University of Sydney, NSW, Australia.
authors.forename: Amgad A
authors.initials: AA
authors.lastname: Zaky
authors.affiliation: Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
authors.affiliation: Department of Medicine, Kolling Institute, University of Sydney, NSW, Australia.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Pollock
authors.affiliation: Department of Medicine, Kolling Institute, University of Sydney, NSW, Australia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Saad
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D000077270:Exenatide; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007674:Kidney Diseases / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D039382:Maternal Nutritional Physiological Phenomena; D009765:Obesity / Q000139:chemically induced / Q000150:complications*; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage* / Q000494:pharmacology; D014886:Weaning
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D014688:Venoms; D000077270:Exenatide