From fatty streak to fatty liver: 33 years of joint publications in the JCI

Abstract

The ASCI is notable for two unique functions--the annual meeting and The Journal of Clinical Investigation. Both have inspired us over the 37 years of our collaborative adventures in research. In this retrospective, we review highlights from our 26 joint papers in the JCI, focusing on two papers that revealed the consequences of lipid accumulation with implications for atherosclerosis and steatohepatitis.

Figure 1. Photographs of a cholesterol-loaded smooth muscle cell (A and B) and a fatty liver (C and D) that were published in our 1977 and 1996 articles in the JCI (5, 6).

A and B show human aortic smooth muscle cells that were incubated with LDL that had been given a net positive charge by covalent linkage with N,N-dimethyl-1,3-propanediamine. After 19 days in culture, the cells were examined either with polarizing microscopy (A) or stained with oil red O and hematoxylin (B). Note that the smooth muscle cell in A shows inclusions that exhibit birefringence with typical formée crosses indicative of liquid crystals of cholesteryl esters as shown in the inset. Parallel dishes of cells incubated with native LDL in the same experiment showed no birefringence and no oil red O staining. Original magnification: ×525 (A); ×3,520 (A, inset); ×600 (B). C and D show the pale color and fat-laden histology of the enlarged fatty liver from a mouse expressing a transgene encoding the nuclear form of SREBP-1a. The liver sample in D was stained with Sudan IV, which stains fatty inclusions orange. Original magnification, ×378.