Alloveda Liver Update: Impact of Hormonal Regulation on Cholesterol Homeostasis |
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Alloveda Liver Update: Impact of Hormonal Regulation on Cholesterol Homeostasis

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Regulation of cholesterol homeostasis is done by a group of endocrine hormones under physiological conditions, hence, hormonal dysregulation is often related to a disturbed cholesterol homeostasis, causing several clinical disorders including atherosclerosis, fatty liver and metabolic syndrome. This regulation of cholesterol metabolism by circulating hormones is mediated by altering levels of relative genes either through their interactions with nuclear receptors or by interfering with bile acid signaling pathways. Thus, elucidation of hormonal regulatory mechanisms can help in recognizing potential effective and selective targets for the management of cholesterol dysfunction.

 

Plethora of evidences suggested that an association is present between thyroid status and cholesterol or lipid metabolism. It has been reported that patients with hypothyroidism have elevated plasma cholesterol and increased lipid accumulation in the liver, which can be normalized with thyroid supplements. Thyroid hormone in physiological levels is essential for maintaining cholesterol homeostasis, which is done by multiple crucial steps including stimulating its hepatic synthesis, serum uptake and the intrahepatic conversion to bile acids. 

 

There is substantial evidence demonstrating better lipid profiles in premenopausal females in contrast to males and these group of women are more protected from hypercholesterolemia-related diseases, including cardiovascular diseases. Assessment of lipid profile has also resulted in similar findings suggesting lower levels of LDL cholesterol and a higher level of HDL cholesterol in premenopausal women. However, these gender variations of lipid profiles disappears after menopause and women even have higher-level LDL as compared to age-matched men. Thus, estrogen replacement therapy can improve lipoprotein profiles in postmenopausal women.

 

Although a negative association is found between obesity and growth hormone, it has the potential to alter lipid metabolism. Numerous studies have proven a remarkable link exists between lower serum levels of growth hormone and non-alcoholic fatty liver disease (NAFLD). Moreover, it has been reported that patients with hypopituitary disorders with growth hormone deficiency are more prone to NAFLD, which can be improved by its supplementation. Hepatic signaling of growth hormone is required for the regulation of intrahepatic lipid and cholesterol metabolism. Studies conducted in experimental animals showed that high-fat diet feeding and obesity suppress pulsatile secretion of growth hormone. Thus, chronic growth hormone therapy improves hepatic lipid peroxidation and lipid metabolism in these populations.

 

Glucagon also affects hepatic cholesterol metabolism. A case representation of a 6-year-old girl with the homozygous form of familial hypercholesterolemia disorder, post portacaval shunt surgery showed significant reduction in LDL and cholesterol synthesis. This alteration is evident to be related with increase of bile acids and the glucagon level, suggestive that glucagon supplementation may ameliorate hepatic lipid metabolism. Moreover, glucagon exhibits a hypolipidemic effect via glucagon receptors that makes making it a potential therapeutic agent for the treatment of dyslipidemia and obesity.

 

Irisin, a novel identified hormone is secreted into the circulation as a cleaved protein product and stimulated by exercise. It mediates the metabolic benefits of exercising by enhancing the browning of subcutaneous adipose tissue, decreasing visceral obesity and ameliorating glucose and cholesterol metabolism. Furthermore, its circulating level is negatively associated with fat mass, fasting glucose and dyslipidemia, as well as intrahepatic total triglyceride levels. 

Source: Mao Z, Li J, Zhang W. Hormonal Regulation of Cholesterol Homeostasis. 2018. Available at: https://www.intechopen.com/books/cholesterol-good-bad-and-the-heart/hormonal-regulation-of-cholesterol-homeostasis

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