Brain hypothalamic proopiomelanocortin and high-fat diet on methylation in offspring as epigenetic modifications

Abstract

Generally, it is believed that genotype and adult lifestyle factors are primary risks of metabolic diseases in life, such as obesity, insulin resistance, and diabetes mellitus. Currently, substantial epidemiological studies and animal experiments indicated maternal overnutrition, such high-fat diet during the critical periods of early life development can significantly increase the predisposition to developing metabolic diseases in later life. However, the underlying mechanism is still not very clear. Recently, epigenetics is hypothesized to be the important molecular basis of the early life overnutrition and abnormal glucose metabolism in adulthood. The fundamental mechanism is that early developmental nutrition can regulate epigenetic modifications of some genes associated with development and metabolism. DNA methylation is the first discovered and an important epigenetic modification. Recent studies suggest that DNA methylation may be the crucial modulators of fetal epigenetic programming in nutrition and metabolic disorders. Furthermore, emerging studies show that brain plays a central role in glucose homeostasis. And the central role of neuropeptides expressed in neurons within nuclei located in the hypothalamus, which can keep balance between food intake and energy expenditure. Most peripheral organs including liver, pancreas, skeletal muscle, and adipose tissue appear to be imprinted by this early imbalanced nutrition. However, investigations into the effects of maternal diet on epigenetic modification of the brain like hypothalamus in the offspring are limited. Therefore, this chapter will focus on brain hypothalamic proopiomelanocortin and high-fat diet on methylation in offspring as epigenetic modifications.