Bile Acids as Drug Candidates
Bile acid derivatives can turn on the vitamin D receptor (VDR) without causing excess calcium buildup, researchers report, a finding that could lead to vitamin D therapies for conditions beyond just bone and skin disorders.
While calcium balance may be the most well-known role of vitamin D, this molecule -through VDR binding- regulates many functions including immunity and cell growth and thus has diverse therapeutic potential. However, while vitamin D-based drugs are effective against some cancers and microbial infections, the risk of excess blood calcium has limited their clinical use.
Bile acids, compounds secreted from the liver that aid in digestion, can also bind to the VDR, though not as strongly. However, Makoto Makishima and colleagues found that derivates of the bile acid LCA (lithocolic acid) are very potent VDR activators. Interestingly, though, these acids did not induce the expression of calcium channels in various cell types.
The researchers then compared the effects of orally-fed vitamin D or LCA derivatives on mice; they found that LCA could promote VDR activation in mice without causing calcium buildup and weight loss that was observed in vitamin D animals. This study suggests bile acid derivates might have solid clinical potential.
Corresponding Author: Makoto Makishima, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan; Phone: +81-3-3972-8199; email: firstname.lastname@example.org
Transgenic Mice Don't Mind Cold Weather
Overexpressing a protein involved in the uptake of fat in muscle of mice can improve their tolerance to cold temperatures, researchers find in a new study that showcases the over-looked role muscle may play in the cold response.
When temperatures drop, mammals respond by generating heat (thermogenesis), through mechanisms like shivering and breaking down 'brown fat' (high energy fat cells that are especially prominent in newborns and hibernating animals). Considering that muscle accounts for over one-third of body mass and muscle activity regulates fat metabolism, Dalan Jensen and colleagues found that increasing the muscle's ability to use fat for energy had a profound impact on its contribution to thermogenesis.
They generated mice overexpressing lipoprotein lipase (LPL), an enzyme that extracts fat from the blood so that it can be used to produce energy instead of sugar. They placed LPL mice in a chamber set to 4 °C (39 °F) and found that they were far more cold tolerant than regular mice; LPL mice could withstand 4 °C for several hours and still maintain normal body temperatures.
This tolerance came from LPL's ability to increase the muscle's ability to oxidize fat, which allow LPL mice to produce more heat than regular animals without increasing their physical activity. Interestingly, this enhanced muscular thermogenesis is akin to how birds -which lack brown fat--produce heat and suggests that mammals, too, have multiple avenues to try and stay warm.
Corresponding Author: Dalan Jensen, Division of Endocrinology, Diabetes, and Metabolism, University of Colorado Denver, Aurora, CO; Phone: 303-724-3962; email: Dalan.Jensen@UCHSC.edu
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at www.asbmb.org