Overnutrition in Mothers and Appetite Regulators in Offspring
Overconsumption of energy-rich food and a sedentary lifestyle make significant contributions to the development of obesity. Over the past several decades, the proportion of people who are overweight or obese has risen sharply. As obesity becomes a global epidemic, the rate of childhood obesity is also increasing. Epidemiological and experimental evidence suggests that programming of obesity may occur following overnutrition during early development. Indeed, intrauterine factors such as abnormal glucose and lipid levels, along with hormonal changes due to maternal obesity may also be important determinants of subsequent obesity risk, even more so than genetic factors, thus contributing to the increased incidence of obesity in children. This highlights the importance of understanding the underlying mechanisms to enable better prevention and to permit development of therapeutic strategies. Over the past 5 years, the focus of research on programming of brain appetite regulation has moved from studying the impact of maternal undernutrition to that of overnutrition, as more and more women around the world enter pregnancy either overweight or obese. The appetite circuits that regulate feeding are highly conserved across mammalian species. Animal models provide an opportunity to investigate the impact of in utero or early postnatal overnutrition while controlling genetic and environmental influences. Rat offspring from mothers rendered obese by access to ‘junk food’ are more likely to overeat and prefer ‘junk food’. They tend to develop very early (weaning age) onset lipid and glucose metabolic disorders, such as hyperlipidemia and glucose intolerance, and these last into adulthood. These offspring also manifest resistance to the anorexigenic effects of leptin. Studies in different species suggest that maternal obesity or consuming a lipid dense diet alter the key hypothalamic neuropeptides controlling food intake and energy homeostasis in offspring in utero, with aberrant neural development continuing after birth. On balance, offspring from obese mothers appear to have more hypothalamic orexigenic neuropeptides and heightened responses to fasting, compared with offspring from lean mothers. Furthermore, short-term overfeeding early in life can significantly contribute to an obese phenotype in individuals. This chapter reviews recent work investigating the impact of maternal obesity and early postnatal overfeeding on hypothalamic appetite circuits and appetite control.
KeywordsMaternal Obesity Junk Food Obese Phenotype Suckling Period Obese Mother
Cocaine- and amphetamine-regulated transcript
High fat diet
Melanocortin 3/4 receptor
Mammalian target of rapamycin
Long form of the leptin receptor
Paraventricular nucleus of the hypothalamus
Suppressor of cytokine signalling
Signal transducer and activator of transcription
Work in the Morris laboratory is supported by the National Health and Medical Research Council of Australia and Diabetes Australia.
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