Within each human cell, molecules called lipids serve as an energy reserve and as structural components of cell membranes. These molecules also do much more, researchers are learning. Lipids help regulate energy metabolism and are involved in communication within and between cells. As messenger molecules, lipids are crucial for the regulation and control of numerous biological processes, including those influencing how drugs affect cell functions. Investigators have begun to focus increasing interest on these versatile molecules, and NIDA recently sponsored the first-ever international conference devoted to the emerging field of inquiry known as lipidomics—the systematic study of the structure and function of lipids.
Lipidomics is a further exploration of research avenues opened by previous NIDA-supported study, explained Dr. Timothy Condon, deputy director of NIDA, in welcoming researchers to the conference, "Targeted Lipidomics: Signaling Lipids and Drugs of Abuse," held in Washington, D.C. "NIDA's marijuana research helped bring into focus the variety of functions of just one group of lipids—the endogenous cannabinoids," Dr. Condon said. "Marijuana-derived cannabinoids contribute to the effects that make marijuana the country's number-one drug of abuse, but cannabinoids that occur naturally in the play a role in obesity, pain, and immune responses to agents like HIV. Other lipids are crucial to the way in which drugs and pathogens behave in the . So it is clear that describing the roles played by lipids and similar compounds will be one of the most important areas of NIDA research in the next decade. This conference will help us develop the agenda for that research," Dr. Condon said.
The conference was organized by Dr. Rao Rapaka of NIDA's Division of Basic Neurosciences and Behavioral Research. "We are learning that lipid interactions are crucial to drug effects, but our understanding of lipids is very superficial," Dr. Rapaka said. "As a first step, lipidomics will bring to bear the same sort of comprehensive research that was used in genomics." Genomics—the scientific effort that led to description of the instructions specified on each of the human 's roughly 30,000 genes—was a scientific milestone, Dr. Rapaka says, but much work remains to understand how those instructions play out in the functioning of the organism. The genes use combinations of nucleic acids to instruct organelles within each cell to synthesize proteins. The proteins, in turn, interact with other chemical compounds—including an estimated 1,000 different lipids, which include energy storage molecules like fatty acids, biologically active sterols such as testosterone and estrogen, and the amide anandamide, a cannabinoid that is active as a chemical messenger in the central nervous system and immune system. Lipids interact with other compounds in temporary or long-lived configurations that have multifarious biological properties and play a role in various cellular activities. "We want to use this conference to develop ideas that will direct a systematic investigation into the structure and function of lipids and their behavior in these complex interactions," Dr. Rapaka said.
At the Washington conference, Dr. Edward Dennis of the University of California-San Diego provided an overview of lipid researchers' major investigative resource—a collaboration of more than 30 researchers at 18 universities known as the Lipid Metabolites and Pathways Strategy (MAPS) Consortium, funded by the National Institute of General Medical Sciences. "We plan to generate 'road maps' that will define how all the lipid components of a cell move through the complex lipidomic network, from biosynthesis to removal, including their important roles as secondary messengers," he explained. Lipid MAPS is divided into focus areas that concentrate on major groupings of lipids, informatics, cell biology, lipid detection and quantitation, and lipid synthesis.
"NIDA's leadership in this important field is invaluable," Dr. Dennis noted. "Lipidomics research is much more than an exercise in basic cell science. The identification of endogenous cannabinoids clearly illustrates the relevance of lipid research to the field of drug abuse, and other discoveries will clarify the complex biochemical relationships between drugs and biological systems ranging from signaling within the central nervous system to immune response."
In addition to the Washington, D.C., conference, NIDA has organized lipid symposia that were held as part of the annual meetings in June of the College on Problems of Drug Dependence in San Juan, Puerto Rico, and the International Cannabinoid Research Society in Paestum, Italy, Dr. Rapaka said.