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.

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