The Legacy of the Great Hunger: Obesity, Hypothalamic Circuits, and the Role of Tryptophan: A Proposed Mechanism

Ireland has elevated rates of obesity; Eurostat EU-SILC data indicate Ireland ranks approximately 12th in the EU for combined overweight and obesity among adults, and the usual explanations including diet, inactivity, and socioeconomic conditions do not fully account for the burden of metabolic disease. Here we argue that part of the answer may originate in The Great Hunger (An Gorta Mór) which took place in Ireland from 1845 to 1852. The blighting of the potato crop by Phytophthora infestans and seven years of malnutrition left most of the rural Irish population without their only meaningful source of tryptophan and vitamin B6, the two nutrients the body needs to synthesize serotonin. Fetuses developing during those years may therefore have formed hypothalamic appetite circuits under reduced serotonin availability, potentially resulting in reduced expression of the receptor that signals satiety in the brain. Evidence from the Dutch Hunger Winter, the Great Chinese Famine, Finland, Ghana, and the Holodomor indicates that this type of prenatal nutritional disruption is consistently associated with elevated obesity and metabolic disease risk in adulthood, and that some of the associated epigenetic differences are detectable in subsequent generations, although germline transmission has not been established in humans. Here we explore potential neural epigenetic mechanisms that may have originated in the Great Hunger and in subsequent generations.