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27-hydroxycholesterol molecule

Role of 27-hydroxycholesterol molecule in obesity

Patients with a non-functional ERα are obese, and those that do not have ERα have increased fat tissue even when they eat the same amount of food, indicating that ERα is the important isoform in the regulation of adipose tissue by oestrogen

A single cholesterol-derived molecule, called 27-hydroxycholesterol (27HC) will increase body fat, even if you do not eat a diet filled with red meat and fried food. That kind of diet, however, will increase the levels of 27HC and body weight.

"We found 27HC directly affects white adipose (fat) tissue and increases body fat, even without eating the diet that increases body fat," reported University of Houston assistant professor of biology, Michihisa Umetani, in the journal Endocrinology. "We hope to develop a new therapeutic approach toward modulating 27HC levels to treat cholesterol and/or oestrogen receptor-mediated diseases such as cardiovascular diseases, osteoporosis, cancer and metabolic diseases," he added, whose lab is part of the UH Center for Nuclear Receptors and Cell Signaling.

The outcomes of the paper, '27-Hydroxycholesterol Promotes Adiposity and Mimics Adipogenic Diet-induced Inflammatory Signaling', could lead to a treatment that reduces the levels of 27HC, which could result in reduced capacity for making fat.

Prior to this research, 27HC was known as an abundant cholesterol metabolite, and Umetani's group has reported its detrimental effects on the cardiovascular system, but its impact on obesity was not well known.

Obesity is one of the main risk factors influencing cardiovascular disease worldwide in both men and women and oestrogen plays a role in both sexes. Menopause in females, with its accompanying decrease in oestrogen, seems to hasten the increase in fat tissue because oestrogen protects against adiposity and body weight gain. In men, oestrogens are also synthesized locally by conversion of testosterone, so they may also play important roles in the development of fat tissues in males.

"Oestrogen receptors (ERα and ERβ) are members of the nuclear receptor superfamily and are present in adipocytes," said Umetani. "Patients with a non-functional ERα are obese, and those that do not have ERα have increased fat tissue even when they eat the same amount of food, indicating that ERα is the important isoform in the regulation of adipose tissue by oestrogen."

The main function of 27HC in the liver is to reduce excess cholesterol. Previously, Umetani discovered that 27HC binds to oestrogen receptors and acts as an inhibitor of ER action in the vasculature. It turned out that the effects by 27HC are tissue-specific, thus 27HC is the first identified naturally-produced selective oestrogen receptor modulator (SERM).

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