Direct Free Fatty Acid Uptake Into Human Adipocytes In Vivo
Open accessAbstract
We sought to assess whether direct uptake of circulating free fatty acids (FFAs) by adipocytes occurs in vivo in overnight postabsorptive humans and, if so, whether there are regional differences in uptake between lean and obese women and men. We used bolus injections of radiolabeled FFA tracers followed by carefully timed adipose tissue biopsies. First, we validated a method to measure direct adipocyte FFA uptake and then quantitated this process using the modified methods in normal-weight postabsorptive men and women. We then used a continuous infusion of radiolabeled FFA to measure direct and indirect (VLDL) regional adipose tissue uptake in obese men and women. Direct FFA uptake was greater in women than men: 8.2 ± 0.6 vs. 4.0 ± 0.5% (P < 0.0001) of FFAs were taken up by subcutaneous adipose tissue, respectively. Abdominal subcutaneous fat took up FFAs more avidly than femoral fat in men, but this did not occur in women. Similar sex and regional difference were found to occur in obese women and men. Gene expression of fatty acid transporters was greater in abdominal than femoral fat in men (P < 0.05) but not in women (P = 0.80). We observed sex- and site-specific recycling of circulating FFAs into subcutaneous fat. This is a novel FFA disposal pathway that may also play a role in the development or maintenance of body fat distribution. Regional variations in facilitated fatty acid transport may contribute to this process.
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Fatty acids can move across cell membranes via a flip-flop mechanism, which seems to be a major mechanism for fatty acid entry into cells for several tissues.
“Because of their nature, FA can move across cell membrane via a “flip-flop” mechanism (97), which seems to be a major mechanism for fatty acids to enter cells for several tissues.”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [97]
The Discussion (page unavailable) identifies “flip-flop” as passive transmembrane transport of free fatty acids, supporting the claim that fatty acids can cross membranes this way. It does not say flip-flop is a major entry mechanism across several tissues; instead, it says that mechanism seemed unlikely to explain the study’s adipocyte findings. (LLM, conf=0.88)
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References 30 · Cited by 127
- Authors
- Shadid, S., Koutsari, C., & Jensen, M. D.
- Affiliations
- Mayo Clinic (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2007-05-01
- Volume
- 56
- Issue
- 5
- Pages
- 1369-1375
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2141377753
- Cited by
- 127
- References
- 30
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 7 · 2017: 8 · 2016: 6 · 2015: 9 · 2014: 7 · 2013: 8 · 2012: 10
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- Deutsches Krebsforschungszentrum
- U.S. Public Health Service (DK45343, DK-40484, DK-50456, R-00585)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 40484, P30DK050456, DK 45343, DK50456, R01DK045343)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- free fatty acid uptake, adipocytes, adipose tissue, fatty acid transporters, sex differences, obesity, regional variation, subcutaneous adipose tissue, abdominal fat, postabsorptive state, VLDL, fatty acid recycling, body fat distribution
- MeSH terms
- Adipose Tissue, Biological Transport, Body Weight, Fatty Acids, Nonesterified, Female, Humans, Male, Obesity, Reference Values, RNA, Tissue Distribution, Adipocytes, Oleic Acid, Palmitic Acid, Fatty Acid Transport Proteins
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