Leptin effects on food intake of offspring from dams with metabolic and nutritional impairments

Author(s)

Giovana Pereira de Oliveira

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
• Defense date: 2021-12-15

Examining board members

Ana Carolina Inhasz Kiss; Jackson Cioni Bittencourt; Carla de Moraes Machado; Débora Cristina Damasceno Meirelles dos Santos

• Advisor: Ana Carolina Inhasz Kiss

Abstract

There is evidence that offspring from diabetic dams show impairments in the structure and function of the main systems involved in the regulation of energy balance. Besides maternal metabolism, maternal nutrition can also compromise these parameters in the offspring. However, the effects of the association of both maternal factors on offspring food intake have not been explored yet. Thus, the aim of this study was to evaluate the effects of chronic central leptin infusion on food intake of male and female offspring of dams with mild hyperglycemia and snack intake during pregnancy and lactation. Sprague-Dawley rats were mated and on pregnancy day (PD) 0 were randomly divided into 2 experimental groups: standard diet or standard diet + snacks, comprised of potato chips and a red fruit-flavored sucrose syrup (1,5%). On PD 7, both experimental groups were then subdivided into normoglycemic dams and dams that were rendered hyperglycemic by streptozotocin administration (STZ, 35mg/kg, i.p.). On postnatal day (PND) 75, 2 males and 2 females from each litter were used and each received a different treatment (saline solution or leptin). Thus, the offspring experimental groups were formed according to maternal metabolism (normoglycemic or hyperglycemic), maternal diet (standard chow or standard chow plus snacks), sex (male or female) and treatment (saline or leptin). On PND 82, animals underwent a stereotaxy surgery for cannula implantation in the lateral cerebral ventricle attached to an osmotic pump (Alzet® model 2001) that released 0.9% saline solution or leptin (1 µg of leptin per day at a rate of 1 µl / hour for 7 consecutive days). Body weight and food intake were monitored daily for 7 days before and 7 days after surgery. On PND 89, rats were killed, and cannula placement was evaluated. All experimental procedures were approved by the local ethics committee (Protocol 1134). Snack intake aggravated the glucose intolerance of hyperglycemic dams and changed the food intake pattern of the offspring. Maternal hyperglycemia during pregnancy increased offspring food intake, and this increase was more pronounced in the offspring of dams fed with snacks. Leptin chronic central infusion reduced offspring food intake and body weight, and the anorectic effect was more pronounced in males. Leptin effects on offspring food intake were modified by maternal metabolism, with offspring from hyperglycemic dams showing a more pronounced reduction on food intake, while effects on body weight were influenced by maternal diet. It is important to emphasize that even an experimental model of mild hyperglycemia, associated with a model with a slight nutritional change, resulted in changes in the offsprings food intake, reinforcing the importance of glycemic and nutritional control of pregnant women to prevent metabolic changes in the offspring and, with this, the transgenerational effect of obesity and related diseases. (AU)

• FAPESP's process: 19/06974-3 - Effects of chronic central leptin infusion on food intake of offspring of rats with mild hyperglicemia
• Grantee: Giovana Pereira de Oliveira
• Support Opportunities: Scholarships in Brazil - Master