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The current global epidemic1 of obesity2-linked diabetes3 and its associated consequences -cardiovascular, neurological and renal(肾脏的) diseases -- is a growing public health problem for which therapeutic4 options are limited. In obesity, fatty acids, derived5 mostly from adipose6 tissue(脂肪组织), alter lipid(脂质) metabolism7 in other tissues such as liver and skeletal muscles. Both impaired8 fatty acid metabolism and glucose9 are hallmarks of diabetes.
In a recent study published in the journal Biochemistry, a research group led by James A. Hamilton, PhD, professor of physiology10, biophysics and radiology at Boston University School of Medicine (BUSM), applied11 novel fluorescent12 methods to measure the rate by which fatty acids bind13 to and move across the fatty acid membrane14 to become metabolized.
"Our study shows that fatty acid entry into cells occurs by diffusion15 without catalysis by a protein previously16 described as a fatty acid transport protein. However, this protein promotes intracellular(细胞间的) metabolism and storage," said Hamilton. "With this advance in basic science, new drugs can be designed that target the exact mechanism17 more precisely18 than currently available drugs."
Previous research has shown that glucose(葡萄糖) transport under the control of insulin is mediated19 by a transport protein called GLUT4. However, how fatty acids enter into cells has been an important unsolved problem, especially whether there are gatekeeper plasma20 membrane proteins that regulate fatty acid translocation across the membrane, thereby21 controlling the supply of fatty acids to the interior of the cell. Although several proteins postulated22 to be fatty acid transporters have now been shown to have other roles, the mechanistic roles of the protein CD36 have remained elusive23 and are widely debated.
After measuring the products of fatty acid metabolism over time, the researchers found that CD36 enhances fatty acid metabolism into triglycerides (fat deposits), without increasing fatty acid translocation across the membrane in a cell line that does not normally synthesize triglycerides(三酸甘油酯). Thus, CD36 increases fatty acid uptake by increasing intracellular metabolism, which promotes diffusion of fatty acids into cells.#p#分页标题#e#
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