Chapter 14 The Developmental Mechanisms of Obesity by Maternal Obesity Long T. Nguyen, Carol A. Pollock and Sonia Saad Abstract Obesity is a major global concern due to its alarming prevalence and associated risks for multiple diseases. The rate of obesity has nearly tripled in the last four decades and amounting evidence is implying a critical role of develop- mental factors before, during and after pregnancy in promoting this global pan- demic. Maternal obesity in particular has been associated with large-for-gestational age babies and increased risk of obesity in adulthood, thus generating a vicious cycle. Studies in animal models demonstrated that such effects of maternal obesity can be detected in the offspring across up to three generations, suggesting a pro- found transgenerational impact. This chapter will discuss critical windows for developmental programming of obesity and possible mechanisms involved such as oxidative stress, mitochondrial dysfunction, placental insults, intrauterine overnu- trition, appetite dysregulation and microbiome. A special focus will be put on epigenetic regulation and the role of sirtuins, which have been suggested to play a central role in the metabolic programming process. Finally, the prospective of intervention therapies for maternal obesity-induced developmental programming will be briefly discussed. Keywords Obesity Á Metabolic disorders Á Pregnancy Á Developmental pro- gramming Á Epigenetic Á Sirtuin Introduction Overweight and obesity, which are generally characterised by greater energy intake than energy expenditure state, with excess energy being stored as fats in adipose tissues, are affecting 25% of the global population, leading to diabetes, hypertension and other chronic diseases. Despite the fundamental role of genetic background in L. T. Nguyen (&) Á C. A. Pollock Á S. Saad Renal Medicine, Kolling Institute Level 9, Royal North Shore Hospital, The University of Sydney, Pacific Hwy, St. Leonard, NSW 2065, Australia e-mail: long.t.nguyen@sydney.edu.au © Springer Nature Switzerland AG 2020 P. S. Tappia et al. (eds.), Pathophysiology of Obesity-Induced Health Complications, Advances in Biochemistry in Health and Disease 19, https://doi.org/10.1007/978-3-030-35358-2_14 241