Splanchnic lipolysis in human obesity
Open accessAbstract
Elevated FFA concentrations have been shown to reproduce some of the metabolic abnormalities of obesity. It has been hypothesized that visceral adipose tissue lipolysis releases excess FFAs into the portal vein, exposing the liver to higher FFA concentrations. We used isotope dilution/hepatic vein catheterization techniques to examine whether intra-abdominal fat contributes a greater portion of hepatic FFA delivery in visceral obesity. Obese women (n = 24) and men (n = 20) with a range of obesity phenotypes, taken together with healthy, lean women (n = 12) and men (n = 12), were studied. Systemic, splanchnic, and leg FFA kinetics were measured. The results showed that plasma FFA concentrations were approximately 20% greater in obese men and obese women. The contribution of splanchnic lipolysis to hepatic FFA delivery ranged from less than 10% to almost 50% and increased as a function of visceral fat in women (r = 0.49, P = 0.002) and in men (r = 0.52, P = 0.002); the slope of the relationship was greater in women than in men (P < 0.05). Leg and splanchnic tissues contributed a greater portion of systemic FFA release in obese men and women than in lean men and women. We conclude that the contribution of visceral adipose tissue lipolysis to hepatic FFA delivery increases with increasing visceral fat in humans and that this effect is greater in women than in men.
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The relative contribution of leg adipose tissue lipolysis to systemic FFA is significantly greater in women than in men.
“The relative contribution of leg adipose tissue lipolysis to systemic FFA is significantly greater in women than men (67, 70)”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [70]
In Systemic FFA kinetics (page unavailable), the lower-body contribution to systemic FFA release is numerically higher in lean women than lean men (20% versus 14%), but equal in obese women and men (28% each). The reported P = 0.02 tests differences among groups, not a significant overall difference between women and men, so the claimed significant sex difference is not established. (LLM, conf=0.86)
Experimental — accuracy not yet measuredVisceral adipose tissue accounts for only a small proportion (c. 6%) of whole body lipolysis in lean individuals.
“Although visceral adipose tissue accounts for only a small proportion (c. 6%) of whole body lipolysis in lean individuals,31 this may explain why chronic glucocorticoid excess causes accumulation of visceral adipose tissue.”
From Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct (2017) · cites this paper as [31]
The Systemic FFA kinetics section reports that the splanchnic bed accounted for 6% ± 1% of systemic FFA release in lean women and men. This supports the small proportion and approximate figure, but the measured quantity is splanchnic FFA release, not visceral adipose tissue's share of whole-body lipolysis. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe contribution of visceral fat to hepatic FFA delivery relative to visceral adipose tissue content is greater in women than in men.
“However, the contribution of visceral fat to hepatic FFA delivery relative to visceral adipose tissue content is greater in women than men (70)”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [70]
The authors pooled data from femoral artery, femoral vein, and hepatic vein catheterization studies to assess variability and sex differences in regional FFA release.
“We pooled data from femoral artery, femoral vein and hepatic vein catheterization studies that included measures of blood flow, body composition and isotopic tracer techniques to assess the variability and sex-differences regional FFA release (33, 65–70).”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [70]
There is no significant difference between women and men in the relative contribution of splanchnic and upper body subcutaneous adipose tissue to systemic FFA release under overnight postabsorptive conditions.
“but there appears to be no significant difference between women and men in the relative contribution of splanchnic and upper body subcutaneous adipose tissue to systemic FFA release under overnight, postabsorptive conditions (70).”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [70]
Only approximately 20% of portal vein FFA delivered to the liver and 14% of systemic FFA delivered to skeletal muscle are derived from lipolysis of VAT in obese subjects.
“In fact, only Ϸ20% of portal vein FFA delivered to the liver and 14% of systemic FFA delivered to skeletal muscle are derived from lipolysis of VAT in obese subjects (20,21).”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [21]
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Santosa, S., Hensrud, D. D., Votruba, S. B., & Jensen, M. D. (2008) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/88.4.1134 · Cited by 62 · see citing works
Self-citationMiyake, T., Abe, M., Tokumoto, Y., Hirooka, M., Furukawa, S., Kumagi, T., Hamada, M., Kawasaki, K., Tada, F., Ueda, T., et al. (2013) · Hepatology International · doi:10.1007/s12072-012-9345-8 · Cited by 59 · see citing works
Free Fatty Acid Storage in Human Visceral and Subcutaneous Adipose Tissue
Ali, A. H., Koutsari, C., Mundi, M., Stegall, M. D., Heimbach, J. K., Taler, S. J., Nygren, J., Thorell, A., Bogachus, L. D., Turcotte, L. P., et al. (2011) · Diabetes · doi:10.2337/db11-0219 · Cited by 58 · see citing works
Self-citationHorton, T. J., Miller, E. K., & Bourret, K. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00491.2005 · Cited by 48 · see citing works
Tschritter, O., Preissl, H., Hennige, A. M., Sartorius, T., Grichisch, Y., Stefan, N., Guthoff, M., Düsing, S., Machann, J., Schleicher, E., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0469 · Cited by 42 · see citing works
Chen, Y., Zheng, X., Ma, D., Zheng, S., Han, Y., Su, W., Liu, W., Xiao, F., Lin, M., Yan, X., et al. (2021) · Fertility and Sterility · doi:10.1016/j.fertnstert.2020.07.027 · Cited by 37 · see citing works
Koutsari, C., Ali, A. H., Nair, K. S., Rizza, R. A., O'Brien, P., Khosla, S., & Jensen, M. D. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0165 · Cited by 35 · see citing works
Self-citationHepatic Fatty Acid Balance and Hepatic Fat Content in Humans With Severe Obesity
Lytle, K. A., Bush, N. C., Triay, J. M., Kellogg, T. A., Kendrick, M. L., Swain, J. M., Gathaiya, N. W., Hames, K. C., & Jensen, M. D. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00875 · Cited by 35 · see citing works
Self-citationInsulin resistance and metabolic flexibility as drivers of liver and cardiac disease in T2DM
Colosimo, S., Mitra, S. K., Chaudhury, T., & Marchesini, G. (2023) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2023.111016 · Cited by 38 · see citing works
Costa, D. N., Santosa, S., & Jensen, M. D. (2025) · Physiological Reviews · doi:10.1152/physrev.00008.2024 · Cited by 34 · see citing works
Self-citationAbdominal fat: does it predict the development of type 2 diabetes?
Gastaldelli, A. (2008) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.5.1118 · Cited by 32 · see citing works
Impact of body composition on very-low-density lipoprotein-triglycerides kinetics
Gormsen, L. C., Nellemann, B., Sørensen, L. P., Jensen, M. D., Christiansen, J. S., & Nielsen, S. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90675.2008 · Cited by 32 · see citing works
Self-citationMorgan-Bathke, M., Chen, L., Oberschneider, E., Harteneck, D., & Jensen, M. D. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00424.2014 · Cited by 30 · see citing works
Self-citationPostabsorptive VLDL‐TG Fatty Acid Storage in Adipose Tissue in Lean and Obese Women
Nellemann, B., Gormsen, L. C., Christiansen, J. S., Jensen, M. D., & Nielsen, S. (2010) · Obesity · doi:10.1038/oby.2009.370 · Cited by 25 · see citing works
Self-citationBülow, J., Gjeraa, K., Enevoldsen, L. H., & Simonsen, L. (2006) · Clinical Physiology and Functional Imaging · doi:10.1111/j.1475-097x.2006.00664.x · Cited by 22 · see citing works
Carbohydrate supplementation: A critical review of recent innovations
Baur, D. A., & Saunders, M. J. (2021) · European Journal of Applied Physiology · doi:10.1007/s00421-020-04534-y · Cited by 22 · see citing works
Similar VLDL-TG Storage in Visceral and Subcutaneous Fat in Obese and Lean Women
Søndergaard, E., Nellemann, B., Sørensen, L. P., Gormsen, L. C., Christiansen, J. S., Ernst, E., Dueholm, M., & Nielsen, S. (2011) · Diabetes · doi:10.2337/db11-0604 · Cited by 17 · see citing works
Self-citationLytle, K. A., Bush, N. C., Triay, J. M., Kellogg, T. A., Kendrick, M. L., Swain, J. M., Gathaiya, N. W., Hames, K. C., & Jensen, M. D. (2021) · Obesity · doi:10.1002/oby.23149 · Cited by 6 · see citing works
Self-citation
- Authors
- Nielsen, S., Guo, Z., Johnson, C. M., Hensrud, D. D., & Jensen, M. D.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Jensen, Michael D.
- Venue
- Journal of Clinical Investigation
- Published
- 2004-06-01
- Volume
- 113
- Issue
- 11
- Pages
- 1582-1588
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC419492
- OpenAlex
- W2010895111
- Cited by
- 933
- References
- 40
- Citations by year
- 2026: 26 · 2025: 26 · 2024: 37 · 2023: 41 · 2022: 41 · 2021: 49 · 2020: 47 · 2019: 33 · 2018: 39 · 2017: 48 · 2016: 37 · 2015: 37 · 2014: 52 · 2013: 54 · 2012: 49
- FWCI
- 16.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Clinic
- Mayo Foundation for Medical Education and Research
- Deutsches Krebsforschungszentrum
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 40484, P30DK050456, DK 45343, DK50456, R37DK040484, R01DK045343, R01DK040484)
- National Center for Research Resources (RR 0585, M01RR000585)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- visceral adipose tissue, free fatty acids, obesity, visceral fat, sex differences, hepatic vein catheterization, isotope dilution, portal vein
- MeSH terms
- Abdomen, Adult, Female, Humans, Kinetics, Leg, Male, Obesity, Body Mass Index, Lipid Metabolism
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