A Recipe for Brain Injury

Abstract

Biomedicine Type 2 diabetes, hypertension, heart disease, stroke, osteoarthritis, cancer. In case the list of health issues associated with a poor diet and obesity is not daunting enough, new research has uncovered another candidate—brain injury. Studying rodent models susceptible to diet-induced obesity, Thaler et al. examined the effect of a high-fat diet on a brain region called the hypothalamic arcuate nucleus, which has a well-established role in feeding and energy balance. Consumption of a high-fat diet caused a spike in hypothalamic inflammation and was accompanied by gliosis, an activation of astrocytes and microglia that normally occurs in response to brain injury. In contrast to high-fat diet-induced peripheral tissue inflammation, which primarily occurs in response to weight gain, brain inflammation occurred rapidly upon high-fat diet initiation. Although initially transient, hypothalamic inflammation reappeared with prolonged consumption of a high-fat diet along with other indicators of brain injury such as increased abundance of neuronal stress proteins, increased neuronal autophagy, and ultimately neuronal loss. In a preliminary analysis, the authors saw radiologic evidence of gliosis in the hypothalamus of obese but not lean humans, consistent with the rodent studies. One hypothesis is that the hypothalamic injury caused by a high-fat diet actively contributes to the progression of obesity and its associated metabolic disorders, but this remains to be experimentally established. J. Clin. Invest. 122 , 153 (2012).