Overweight children and adults have low levels in their blood of a protein known as SHGB, which transports sex steroids and regulates their entry into tissues. Low levels of SHGB are a marker of the metabolic syndrome, a combination of medical disorders that increase an individual’s risk of developing type 2 diabetes and heart disease. An explanation as to why low levels of SHGB are such a good marker of the metabolic syndrome are now provided by Geoffrey Hammond and colleagues at the University of British Columbia, Vancouver.
In the study, exposure to glucose and fructose (monomeric sugar building blocks of carbohydrates) reduced the production of SHGB in vitro by a human liver cell line and in vivo by the liver of mice engineered to express human SHGB. Decreased production of SHGB was mediated by decreased expression of a protein that stimulates the gene that makes SHGB (HNF-4-alpha) and was associated with increased amounts of the fat palmitate in the liver cells. Importantly, glucose- and fructose-induced decreases in SHGB production were prevented by inhibiting palmitate generation. These data provide a mechanistic link between excess sugar and carbohydrate consumption and decreased levels of SHGB, indicating the reason it is a good marker of the metabolic syndrome.
TITLE: Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone–binding globulin gene
AUTHOR CONTACT:
Geoffrey L. Hammond
Child & Family Research Institute, Vancouver, British Columbia, Canada.
Phone: (604) 875-2435; Fax: (604) 875-2496; E-mail: ghammond@cw.bc.ca .
MEDIA CONTACT:
Jennifer Kohm
Director, Communications
Child & Family Research Institute, Vancouver, British Columbia, Canada.
Phone: (604) 875- 2401; E-mail: jkohm@cw.bc.ca .
View the PDF of this article at: https://www.the-jci.org/article.php?id=32249
Journal of Clinical Investigation