# Robert K. Ockner
**Robert K. Ockner** (R. K. Ockner; Robert Keith Ockner, July 30, 1936 – September 26, 2022) was an American physician-scientist in hepatology at the [University of California, San Francisco](https://www.edgepedia.org/university-of-california-san-francisco) (UCSF), known for discovering the intracellular fatty acid-binding proteins and for proposing an albumin receptor mechanism for hepatic uptake of fatty acids.[1](https://journals.lww.com/hep/fulltext/2023/02000/in_memoriam__robert_k__ockner,_md.30.aspx) • [2](https://www.aasld.org/robert-k-ockner-md-faasld) He served as president of the American Association for the Study of Liver Diseases (AASLD) in 1984.[2](https://www.aasld.org/robert-k-ockner-md-faasld)
| Fact | Detail |
|---|---|
| Born; died | July 30, 1936, New Kensington, Pennsylvania; September 26, 2022, age 86[1](https://journals.lww.com/hep/fulltext/2023/02000/in_memoriam__robert_k__ockner,_md.30.aspx) |
| Training | BA magna cum laude, Pomona College, 1957; MD cum laude, Harvard Medical School, 1961; research fellowship under Kurt Isselbacher at the NIH[1](https://journals.lww.com/hep/fulltext/2023/02000/in_memoriam__robert_k__ockner,_md.30.aspx) |
| UCSF career | GI faculty from 1968; led the gastroenterology division 1983–1990; director of the NIH-funded Liver Center 1983–1998[2](https://www.aasld.org/robert-k-ockner-md-faasld) |
| Signature work | 1972 Science paper identifying a cytosolic fatty acid-binding protein in intestine, liver, myocardium, adipose tissue, and kidney[3](https://doi.org/10.1126/science.177.4043.56) |
| Field contribution | Named and characterized the fatty acid-binding proteins (FABPs), now a family of about ten mammalian genes |[4](https://onlinelibrary.wiley.com/doi/10.1111/jcmm.17703) • [5](https://www.annualreviews.org/content/journals/10.1146/annurev-nutr-062220-112240)
| Society role | President of the AASLD, 1984; Editor-in-Chief of Gastroenterology, 1981–1986[2](https://www.aasld.org/robert-k-ockner-md-faasld) • [6](https://www.thearknewspaper.com/live/noted-ucsf-researcher-robert-ockner-was-former-reed-schools-trustee) |
| Later career | Closed his research career with a 2004 monograph on metabolism, energetics, and signal transduction[2](https://www.aasld.org/robert-k-ockner-md-faasld) |
## Training and early career
Ockner graduated BA magna cum laude from [Pomona College](https://www.edgepedia.org/pomona-college) in 1957 and MD cum laude from Harvard Medical School in 1961.[1](https://journals.lww.com/hep/fulltext/2023/02000/in_memoriam__robert_k__ockner,_md.30.aspx) As a medical student working with [Rudi Schmid](https://www.edgepedia.org/rudi-schmid) at the Thorndike Memorial Laboratories, Boston City Hospital, he developed, according to an in memoriam published in *Hepatology*, an animal model of porphyria caused by hexachlorobenzene poisoning, published in Nature.[1](https://journals.lww.com/hep/fulltext/2023/02000/in_memoriam__robert_k__ockner,_md.30.aspx)
Between 1961 and 1968 he completed residency in internal medicine at Harvard Medical Services, Boston City Hospital, and a clinical fellowship in gastroenterology at the National Institutes of Arthritis and Metabolic Diseases, with a research fellowship under Kurt Isselbacher.[1](https://journals.lww.com/hep/fulltext/2023/02000/in_memoriam__robert_k__ockner,_md.30.aspx) In 1968 he joined the gastroenterology faculty at UCSF, where he rose to full professor.[2](https://www.aasld.org/robert-k-ockner-md-faasld)
## Career and leadership at UCSF
He served as chief of the division from 1983 until 1990, a period that included establishing UCSF's liver transplant program; the obituary in [Hepatology](https://www.edgepedia.org/hepatology) describes the sequence as Chief of Clinical Gastroenterology until 1983, then Director of the Division until 1990.[2](https://www.aasld.org/robert-k-ockner-md-faasld) • [1](https://journals.lww.com/hep/fulltext/2023/02000/in_memoriam__robert_k__ockner,_md.30.aspx) Between 1983 and 1998 he was director of the NIH-funded Liver Center at UCSF.[2](https://www.aasld.org/robert-k-ockner-md-faasld)
His research produced 94 publications in lipid and lipoprotein metabolism.[2](https://www.aasld.org/robert-k-ockner-md-faasld) He closed his research career with a 2004 monograph, *Integration of Metabolism, Energetics, and Signal Transduction: Unifying Foundations in Cell Growth and Death, Cancer, Atherosclerosis, and Alzheimer Disease*.[2](https://www.aasld.org/robert-k-ockner-md-faasld)
## Representative work
His [1972 Science paper](https://doi.org/10.1126/science.177.4043.56), "A Binding Protein for Fatty Acids in Cytosol of Intestinal Mucosa, Liver, Myocardium, and Other Tissues," identified a protein of molecular weight approximately 12,000 that binds long-chain fatty acids in the cytosol of intestinal mucosa, liver, myocardium, adipose tissue, and kidney.[3](https://doi.org/10.1126/science.177.4043.56) Binding is noncovalent and greater for unsaturated than for saturated and medium-chain fatty acids, and greater than for other anions tested, including sulfobromophthalein, so it does not depend on negative charge alone.[3](https://doi.org/10.1126/science.177.4043.56) The paper proposed that the binding protein may explain previously observed differences in intestinal absorption among fatty acids and may participate in the utilization of long-chain fatty acids by many mammalian tissues.[3](https://doi.org/10.1126/science.177.4043.56)
## The fatty acid binding protein discovery and its legacy
The protein was named "fatty acid binding protein" because it showed tight association with a radiolabelled long-chain fatty acid.[4](https://onlinelibrary.wiley.com/doi/10.1111/jcmm.17703) A companion 1972 [Gastroenterology](https://www.edgepedia.org/gastroenterology) paper reported the same roughly 12,000 molecular weight cytosolic protein across the same tissues.[7](https://doi.org/10.1016/s0016-5085(72)80115-x) A 1974 Journal of Clinical Investigation paper isolated the intestinal protein by gel filtration and isoelectric focusing and showed complete immunochemical identity with the 12,000 molecular weight fatty-acid-binding fractions of liver, myocardium, and adipose tissue.[8](https://doi.org/10.1172/jci107768) Intestinal FABP concentration in villi was approximately three times greater than in crypts, and significantly higher in animals on high-fat diets than low-fat diets.[8](https://doi.org/10.1172/jci107768) A 1982 [Journal of Biological Chemistry](https://www.edgepedia.org/journal-of-biological-chemistry) paper isolated liver FABP with molecular weight 12,080 ± 80, existing in several immunochemically identical forms differing in isoelectric pH; FABP-bound fatty acids accounted for 60% of total cytosolic long-chain fatty acids, and cytosolic FABP concentration in mature female rats (51.7 ± 3.0 µg/mg protein) exceeded that of mature males (39.8 ± 4.0, p < 0.05).[9](https://doi.org/10.1016/s0021-9258(18)34463-6)
The 1972 description of liver-FABP (FABP1) was the first FABP described; L-FABP is expressed at 2–5% of cytosolic protein in liver, intestine, and kidney.[10](https://pmc.ncbi.nlm.nih.gov/articles/PMC2939181/) Later scholarship cites the 1972 Science paper as a foundational work of the FABP field.[11](https://doi.org/10.1007/978-1-4615-3936-0_1) Five decades on, ten FABP protein-coding genes have been identified in the human genome (FABP1–9 and FABP12), originally named for the tissue of first identification; FABPs are a family of 14–15 kDa carriers of small hydrophobic molecules, now understood as sensors, conveyors, and modulators of cellular lipid handling rather than master regulators.[5](https://www.annualreviews.org/content/journals/10.1146/annurev-nutr-062220-112240) • [4](https://onlinelibrary.wiley.com/doi/10.1111/jcmm.17703) Mouse studies show the physiological weight of the discovery: L-FABP gene ablation produces age- and sex-dependent weight gain and increased fat mass, exacerbated by a high-fat diet,[10](https://pmc.ncbi.nlm.nih.gov/articles/PMC2939181/) and LFABP-null mice show diminished hepatic fatty acid β-oxidation in the fasted state that is not due to diminished oxidative capacity or decreased PPARα.[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC2963392/)
## Albumin receptor hypothesis and hepatic uptake
In a [1981 Science paper](https://www.science.org/doi/10.1126/science.6258226), kinetic analysis of the uptake of carbon-14-labeled oleate in single-pass perfused rat liver, together with saturable and specific binding of iodine-125-labeled albumin to hepatocytes in suspension, suggested the existence of a receptor for albumin on the liver cell surface.[13](https://www.science.org/doi/10.1126/science.6258226) The putative receptor appeared to mediate uptake of albumin-bound fatty acids and might account for the efficient hepatic extraction of many substances tightly bound to albumin.[13](https://www.science.org/doi/10.1126/science.6258226) A 1983 review by the group reported that iodine-125-albumin binds specifically, saturably, and reversibly to isolated hepatocytes, adipocytes, and erythrocytes, and that uptake of albumin-bound ligands is mediated primarily by direct interaction of the albumin-ligand complex with the hepatocyte surface.[14](https://doi.org/10.1152/ajpgi.1983.245.1.g13)
## Honors, editorial and society roles
Ockner was elected president of the AASLD in 1984[2](https://www.aasld.org/robert-k-ockner-md-faasld) and received the Western Gastroenterological Society's Research Prize in 1980.[6](https://www.thearknewspaper.com/live/noted-ucsf-researcher-robert-ockner-was-former-reed-schools-trustee) He was Associate Editor of the Journal of Lipid Research (1972–1976), Editor-in-Chief of Gastroenterology (1981–1986), and Co-Editor of Progress in Liver Diseases (1991–1997).[1](https://journals.lww.com/hep/fulltext/2023/02000/in_memoriam__robert_k__ockner,_md.30.aspx) He chaired the Gastroenterology and Clinical Nutrition Review Group at the NIH from 1980 to 1981 and served on the [Governing Board](https://www.edgepedia.org/governing-board) of the [American Gastroenterological Association](https://www.edgepedia.org/american-gastroenterological-association) from 1989 to 1992.[1](https://journals.lww.com/hep/fulltext/2023/02000/in_memoriam__robert_k__ockner,_md.30.aspx) In 2005 he received a Mentors Research Scholar Award from the AGA.[1](https://journals.lww.com/hep/fulltext/2023/02000/in_memoriam__robert_k__ockner,_md.30.aspx)
## References
1. In memoriam: Robert K. Ockner, MD. Hepatology, February 2023. https://journals.lww.com/hep/fulltext/2023/02000/in_memoriam__robert_k__ockner,_md.30.aspx
2. Robert K. Ockner, MD, FAASLD. AASLD tribute page. https://www.aasld.org/robert-k-ockner-md-faasld
3. A Binding Protein for Fatty Acids in Cytosol of Intestinal Mucosa, Liver, Myocardium, and Other Tissues. Science, 1972. https://doi.org/10.1126/science.177.4043.56
4. Importance of fatty acid binding proteins in cellular function and organismal metabolism. Journal of Cellular and Molecular Medicine. https://onlinelibrary.wiley.com/doi/10.1111/jcmm.17703
5. The Multifunctional Family of Mammalian Fatty Acid–Binding Proteins. Annual Review of Nutrition, 2024. https://www.annualreviews.org/content/journals/10.1146/annurev-nutr-062220-112240
6. Noted UCSF researcher Robert Ockner was former Reed schools trustee. The Ark. https://www.thearknewspaper.com/live/noted-ucsf-researcher-robert-ockner-was-former-reed-schools-trustee
7. https://doi.org/10.1016/s0016-5085(72)80115-x
8. Fatty Acid-Binding Protein in Small Intestine: Identification, Isolation, and Evidence for Its Role in Cellular Fatty Acid Transport. Journal of Clinical Investigation, 1974. https://doi.org/10.1172/jci107768
9. https://doi.org/10.1016/s0021-9258(18)34463-6
10. Liver Fatty Acid Binding Protein and Obesity. https://pmc.ncbi.nlm.nih.gov/articles/PMC2939181/
11. Historic overview of studies on fatty acid-binding proteins. Springer. https://doi.org/10.1007/978-1-4615-3936-0_1
12. Tissue-specific Functions in the Fatty Acid-binding Protein Family. Journal of Biological Chemistry thematic series. https://pmc.ncbi.nlm.nih.gov/articles/PMC2963392/
13. Receptor for Albumin on the Liver Cell Surface May Mediate Uptake of Fatty Acids and Other Albumin-Bound Substances. Science, 1981. https://www.science.org/doi/10.1126/science.6258226
14. Hepatic uptake of albumin-bound substances: albumin receptor concept. American Journal of Physiology, 1983. https://doi.org/10.1152/ajpgi.1983.245.1.g13
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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in physiology › Cellular and molecular physiologists*
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