Association between duration of obesity and severity of ovarian dysfunction in rat- cafeteria diet approach Saranya Kannan, Divya Srinivasan, Prasanth Balan Raghupathy, Ravi Sankar Bhaskaran ⁎ Department of Endocrinology, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India Received 6 February 2019; received in revised form 16 May 2019; accepted 16 May 2019 Abstract Consumption of unhealthy, energy-dense palatable food during early age leads to obesity in children and the onset of obesity during childhood has a profound effect on the reproductive health of women. In this study, the mechanism underlying diet-induced obesity on ovarian dysfunction was studied by exposing rats to cafeteria diet (CAFD) for two different durations. For that purpose, 21-day-old female Sprague Dawley rats were fed ad libitum with a standard diet (control group) and a cafeteria diet (CAFD group) for a period of 20 weeks (20 W) and 32 weeks (32 W). We observed obesity, hyperglycemia, hyperlipidemia, hyperleptinemia and hypoadiponectinemia in CAFD fed groups. Hyperinsulinemia, hypergonadotrophism, hypertestosteronemia and hyperprogesteronemia were observed in the 20 W-CAFD group. Conversely, in the 32 W-CAFD group hypersecretion declined to hyposecretion. The levels of estradiol remained low during both time periods. The duration of estrous cycle was extended in the CAFD fed rats. The ovary weight was higher in the 20 W- CAFD fed rats but it was drastically reduced over a longer duration cafeteria diet feeding. In the 20 W-CAFD fed rats, the protein levels of LHR, StAR, CYP11A1, 3β- HSD and 17β-HSD were increased but FSHR and CYP19A1 levels were decreased in the ovary. On the other hand, gonadotropin receptor and the protein levels of steroidogenic enzymes were decreased in the ovary of 32 W-CAFD fed rats. We conclude that the duration of energy-dense diet consumption has differential regulatory mechanism in altering the ovarian steroid production. In 20 W-CAFD fed rats, hypergonadotropic condition was observed whereas, 32 W-CAFD consumption induced hypogonadotropic hypogonadism. © 2019 Elsevier Inc. All rights reserved. Keywords: Obesity; Cafeteria diet; Hypogonadotropic hypogonadism; Hypoinsulinemia; Ovarian steroidogenesis; Ovarian dysfunction 1. Introduction Over the last century, eating habits have dramatically changed due to modernization in the food industry such as producing more processed, affordable, and effectively marketed food than ever before, which provided an easy access to palatable and high calorie food [1]. Consumption of these energy-dense foods increases the body mass index (BMI) and prevalence of childhood obesity [2,3]. Body weight is regulated by the homeostatic control of energy balance [4]. Therefore, any factor that raises energy intake or decreases energy expenditure may cause obesity [5]. Overeating is the major factor which increases energy intake; palatability plays the key role in promoting the desire to eat independent of actual energy needs [6]. The use of high energy, palatable, self-selected diets, known globally as cafeteria diet (CAFD), was introduced in the late seventies as an experimental model for the study of obesity [7,8]. Cafeteria diet model closely reflects the modern human condition of early onset obesity [9]. Obesity is associated with serious reproductive sequelae, and it is a major contributor to a variety of underlying aetiologies associated with infertility [10]. Although most obese women are not infertile, obesity has a negative impact on fecundity and fertility [11,12]. Several studies showed that excess body fat interferes with reproductive function in females in many models of obesity [13–16]. Evidences show that CAFD administered from weaning induces obesity which reduced reproductive capability in adult female rats [17,18]. It has been reported that CAFD-induced obesity impaired ovarian function in rats by reducing the ovulation rate and serum estradiol level [17,19]. Gaining excess weight in childhood likely paves way to lifelong overweight and obesity [20]. In the modern world increased intake of high-calorie palatable food occurs at an early age that leads to increased exposure to obesity over a long-term duration which may have severe impact on the reproductive system. Unfortunately, fertility and reproduction have a well-defined biological time interval. Moreover, both the degree and duration of obesity increase the risk of Available online at www.sciencedirect.com ScienceDirect Journal of Nutritional Biochemistry 71 (2019) 132 – 143 ⁎ Corresponding author at: Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai - 600 113. E-mail addresses: saranyakalai.kanan@gmail.com (S. Kannan), divyasrinivasan210893@gmail.com (D. Srinivasan), prasanth26394@gmail.com (P.B. Raghupathy), bravisankar@yahoo.com (R.S. Bhaskaran). https://doi.org/10.1016/j.jnutbio.2019.05.012 0955-2863/© 2019 Elsevier Inc. All rights reserved.