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A Review on the Sex Difference in Lipotoxicity in Peripheral Nerves

Masahiro Ogawa

Obesity is caused as the consequence of positive energy balance, which increases the amount of lipid in adipose tissue. The intake of excessive amounts of fatty acids is considered to be a risk factor for cardiovascular diseases, insulin resistance, dyslipidemia, and obesity. Males and females experience many diseases and disorders differently. Sex hormones, such as estrogen, progesterone, and androgen, contribute to the sex differences in body weight and metabolism between males and females and are thought to be responsible for sex-specific differences. Several studies have shown that the sex-specific adverse effects were observed in peripheral nerves. This review focuses on the sex difference in lipotoxicity in peripheral nerves. High-fat diet feeding promotes oxidative stress and inflammation in animal models. In male mice fed the high-fat diet, the pathogenesis of neuropathy is enhanced in the sciatic nerves. The high-fat diet induced apoptosis in the sciatic nerves of male, but not female. In ovariectomized female mice, a high-fat diet induces the apoptosis marker. On the other hand, estrogen attenuates high-fat dietinduced apoptosis markers in the sciatic nerve of ovariectomized female mice. Therefore, there indicate that estrogen is a key factor for the sex difference in peripheral nervous disorder. In vitro studies have reported that estrogen-activated ERα prevents the fatty acid-induced oxidative stress and inflammation and has the inhibitory effects of fatty acid-enhanced apoptosis and autophagy in peripheral nerves. On the other hand, a recent study has reported that ERβ promotes autophagy in neural cells. These suggest that ERβ may have the opposite effects of ERα in neural cells. Further studies are needed to understand the role of ER isoforms in neuron injury.