Early life origins of metabolic disease: Developmental programming of hypothalamic pathways controlling energy homeostasis

Abstract

A wealth of animal and human studies demonstrate that perinatal exposure to adverse metabolic conditions - be it maternal obesity, diabetes or under-nutrition - results in predisposition of offspring to develop obesity later in life. This mechanism is a contributing factor to the exponential rise in obesity rates. Increased weight gain in offspring exposed to maternal obesity is usually associated with hyperphagia, implicating altered central regulation of energy homeostasis as an underlying cause. Perinatal development of the hypothalamus (a brain region key to metabolic regulation) is plastic and sensitive to metabolic signals during this critical time window. Recent research in non-human primate and rodent models has demonstrated that exposure to adverse maternal environments impairs the development of hypothalamic structure and consequently function, potentially underpinning metabolic phenotypes in later life. This review summarizes our current knowledge of how adverse perinatal environments program hypothalamic development and explores the mechanisms that could mediate these effects.

Resveratrol supplementation of high‐fat diet‐fed pregnant mice promotes brown and beige adipocyte development and prevents obesity in male offspring

“…), impaired hippocampal neurogenesis (Tozuka et al . ; Dearden & Ozanne, ), adrenal and thyroid dysfunction (Franco et al . ), as well as obesity and insulin resistance (Boyle et al .…”

Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets

“…Currently, one of the main environmental insults on human health is the food we eat (Lustig et al., 2012). Indeed, chronic diseases are on the rise globally, due in part to aging populations (Christensen et al., 2009) but also due to the increasing consumption of unhealthy diets dominated by highly processed, low-cost foods (Dearden and Ozanne, 2015, Lustig et al., 2012). For example, sugar consumption has tripled over the last 50 years and is linked to a range of detrimental health outcomes (Lustig et al., 2012).…”

“…In humans and other mammals, there is a wealth of epidemiological and experimental evidence that both under- and over-nutrition in early life can profoundly influence later-life health and survival. Long-term effects arise during development, potentially in early adulthood, and can be transmitted from parent to offspring (Dearden and Ozanne, 2015, Fernandez-Twinn et al., 2014, Gillman, 2005, Hardikar et al., 2015, Hirko et al., 2015, Langley-Evans, 2006). Importantly, even small, persistent effects can have important societal consequences due to the sheer number of people consuming unhealthy diets (Lustig et al., 2012).…”

Birthdate of parvalbumin-neurons in the Parvafox-nucleus of the lateral hypothalamus

“…The hypothalamus is known to play a pivotal role in the regulation of vital functions (Dearden and Ozanne, 2015;MacKay and Abizaid, 2014).…”