Maternal Obesity Has Gender‐Specific Effects on Mouse Offspring Insulin Sensitivity After β3 Adrenergic Agonist Treatment

Abstract

IntroductionMaternal obesity has negative effects on offspring metabolism and adipose tissue, a central organ for energy homeostasis and body weight regulation, is a putative target of treatment in this context. Our aim was to evaluate putative effects of maternal obesity on offspring metabolism and adaptation after pharmacological induction of adipose tissue lipolysis and remodeling.MethodsThis project was approved by the institution Animal Ethics Committee (process number 40/2016). Eight weeks‐old female mice were randomly divided in two groups: high fat and high sugar diet or balanced diet. At sixth week, before mating, a glucose tolerance test (GTT) was performed. After conception, lean and obese female mice were single‐housed and their respective diets were maintained. Offspring received ad libitum balanced diet from weaning to eight weeks, when a GTT was performed. After, they were randomly divided between two treatments: CL 316,243 (1mg/kg/day), a β3 adrenergic receptor agonist, or saline i.p. during 10 days. In this period, energy intake was measured each day. An insulin tolerance test (ITT) was performed on the seventh day of treatment. On the last day of treatment, energy expenditure was analysed by indirect calorimetry in a 24 hours period. Both male and female offspring were studied. Data was analyzed by unpaired t test or two‐way ANOVA followed by Tukey post‐hoc test. Each group had 3–5 animals and a p‐value < 0.05 was considered statistically significant.ResultsAt sixth week, obese females were 4.9 g heavier than lean females (p=0.0001). Obese females also had impaired glucose tolerance, showing a 57.7% increase in area under the curve of blood glucose through time (p=0.0028). Glucose tolerance was also reduced in obese female offspring (lean dam 28849 AUC vs. obese dam 42676 AUC, p=0.0131), while male obese dam offspring had a better performance on this test (lean dam 34634 AUC vs. obese dam 22969 AUC, p=0.0410). Energy intake during the 10 days treatment was increased with adrenergic agonist administration in male offspring, for both lean and obese dams (p=0.0499), while obese dam female offspring had smaller consumption, independent of the treatment (p=0.0076). At seven days of treatment, glucose decay ratio improved in male obese dam offspring (p=0.0368). However, in female offspring, treatment didn't improved insulin response, and obese offspring had worst results, independent of the treatment (p=0.0364). After ten days of treatment, energy expenditure was analysed by indirect calorimetry. For female offspring, CL316,243 treatment per se increase respiratory exchange, independent of the maternal diet (p=0.0387), indicating major oxidation of carbohydrates. Obese female offspring had reduced ambulatory activity after treatment (p=0.0194) and showed no difference in O2 consumption. There were no differences for male offspring.ConclusionA lack of properly response to CL 316,243 in obese dam female offspring, which indicates poor communication between sympathetic nerves and adipose tissue, is a putative cause for metabolic alterations in adulthood, and can be a target for treatment and prevention of metabolic syndrome.Support or Funding InformationFAPESP 2016/08202‐0This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.