Energy expenditure, sex, and endogenous fuel availability in humans
Open accessAbstract
Adipose tissue lipolysis supplies circulating FFAs, which largely meet lipid fuel needs; however, excess FFAs, can contribute to the adverse health consequences of obesity. Because "normal" FFA release has not been well defined, average (mean of 4 days) basal FFA release and its potential regulation factors were measured in 50 lean and obese adults (25 women). Resting energy expenditure (REE), but not body composition, predicted most of the interindividual variation in FFA release. There was a significant, positive linear relationship between palmitate release and REE; however, women released approximately 40% more FFA than men relative to REE. Neither plasma palmitate concentrations nor respiratory quotient by indirect calorimetry differed between men and women. Glucose release rates were not different in men and women whether related to REE or fat free mass. These findings indicate that nonoxidative FFA clearance is greater in women than in men. This could be an advantage at times of increased fuel needs. We conclude that "normal" adipose tissue lipolysis is different in men and women and that the fuel export role of adipose tissue in obesity will need to be reassessed.
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Physical activity increases energy expenditure and alters substrate utilization based on intensity and duration.
“Physical activity increases energy expenditure and alters substrate utilization based on the intensity and duration (32, 160).”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [32]
The Introduction says exercise stimulates fat oxidation, and the discussion following Figure 3 says energy expenditure and fat oxidation increase almost immediately during exercise. Our copy does not say that substrate utilization varies with exercise intensity and duration; the study focuses on resting fuel availability. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSystemic FFA release rates relative to resting energy expenditure are about 40% greater in women than in men.
“Systemic FFA release rates relative to REE are ~40% greater in women than men (32, 71)”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [32]
Plasma FFA concentrations are only about 10% greater in women than in men.
“however plasma FFA concentrations are only ~10% greater in women”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [32]
Endogenous glucose production rates are linearly related to fat-free mass, and this relationship is not different between men and women.
“Endogenous glucose production rates are linearly related to FFM, and the relationship is not different between men and women (32, 71).”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [32]
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Koutsari, C., Basu, R., Rizza, R. A., Nair, K. S., Khosla, S., & Jensen, M. D. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1651 · Cited by 51 · see citing works
Self-citationMetabolic characteristics of human subcutaneous abdominal adipose tissueafter overnight fast
Frayn, K. N., & Humphreys, S. M. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00527.2011 · Cited by 51 · see citing works
Berk, E. S., Kovera, A. J., Boozer, C. N., Pi-Sunyer, X., & Albu, J. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2411 · Cited by 49 · see citing works
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Storage Rates of Circulating Free Fatty Acid Into Adipose Tissue During Eating or Walking in Humans
Koutsari, C., Mundi, M. S., Ali, A. H., & Jensen, M. D. (2012) · Diabetes · doi:10.2337/db11-0748 · Cited by 38 · see citing works
Self-citationSex Differences in Energy Metabolism: A Female-Oriented Discussion
Sanchez, B. N., Volek, J. S., Kraemer, W. J., Sáenz, C., & Maresh, C. M. (2024) · Sports Medicine · doi:10.1007/s40279-024-02063-8 · Cited by 38 · see citing works
Do estrogens enhance activation of brown and beiging of adipose tissues?
Frank, A. P., Palmer, B. F., & Clegg, D. J. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.09.026 · Cited by 38 · see citing works
Energy expenditure, insulin, and VLDL-triglyceride production in humans
Gormsen, L. C., Jensen, M. D., Schmitz, O., Møller, N., Christiansen, J. S., & Nielsen, S. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m600175-jlr200 · Cited by 38 · see citing works
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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-citationPioglitazone increases non-esterified fatty acid clearance in upper body obesity
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Self-citationCosta, D. N., Santosa, S., & Jensen, M. D. (2025) · Physiological Reviews · doi:10.1152/physrev.00008.2024 · Cited by 34 · see citing works
Self-citationMagkos, F., Mohammed, B. S., Patterson, B. W., & Mittendorfer, B. (2009) · Metabolism · doi:10.1016/j.metabol.2009.03.023 · Cited by 32 · see citing works
Koppo, K., Larrouy, D., Marqués, M.-A., Berlan, M., Bajzová, M., Polak, J., de Voorde, J. V., Bülow, J., Lafontan, M., Crampes, F., et al. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00767.2009 · Cited by 31 · see citing works
Sasaki, N., Maeda, R., Ozono, R., Yoshimura, K., Nakano, Y., & Higashi, Y. (2022) · Hypertension Research · doi:10.1038/s41440-022-00987-0 · Cited by 30 · see citing works
Fappi, A., & Mittendorfer, B. (2019) · Proceedings of The Nutrition Society · doi:10.1017/s0029665119001022 · Cited by 29 · see citing works
Gender-specific differences in energy metabolism during the initial phase of critical illness
Drolz, A., Wewalka, M., Horvatits, T., Fuhrmann, V., Schneeweiß, B., Trauner, M. A., & Zauner, C. (2014) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2013.287 · Cited by 28 · see citing works
Montastier, É., Ye, R. Z., Noll, C., Bouffard, L., Fortin, M., Frisch, F., Phoenix, S., Guérin, B., Turcotte, É. E., Lewis, G. F., et al. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00619.2020 · Cited by 27 · see citing works
Moran, A., Basu, R., Milla, C. E., & Jensen, M. D. (2004) · Metabolism · doi:10.1016/j.metabol.2004.06.015 · Cited by 27 · see citing works
Self-citationPatel, J. V., Cummings, D. E., Girod, J. P., Mascarenhas, A. V., Hughes, E. A., Gupta, M. K., Lip, G. Y. H., Reddy, S. S. K., & Brotman, D. J. (2006) · Journal of Negative Results in BioMedicine · doi:10.1186/1477-5751-5-14 · Cited by 26 · see citing works
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Jensen, M. D., Bajnárek, J., Lee, S. Y., Nielsen, S., & Koutsari, C. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m900021-jlr200 · Cited by 25 · see citing works
Self-citationBush, N. C., Basu, R., Rizza, R. A., Nair, K. S., Khosla, S., & Jensen, M. D. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2285 · Cited by 22 · see citing works
Self-citationGoree, L. L. T., Darnell, B., Oster, R., Brown, M. A., & Gower, B. (2009) · Obesity · doi:10.1038/oby.2009.248 · Cited by 22 · see citing works
Increased VLDL-TG Fatty Acid Storage in Skeletal Muscle in Men With Type 2 Diabetes
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Self-citationSystemic Free Fatty Acid Disposal Into Very Low-Density Lipoprotein Triglycerides
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Self-citationInsulin clearance is different in men and women
Jensen, M. D., Nielsen, S., Gupta, N., Basu, R., & Rizza, R. A. (2011) · Metabolism · doi:10.1016/j.metabol.2011.08.009 · Cited by 21 · see citing works
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Self-citationŠarac, I., Backhouse, K., Shojaee‐Moradie, F., Stolinski, M., Robertson, M. D., Bell, J. D., Thomas, E. L., Hovorka, R., Wright, J., & Umpleby, A. M. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3248 · Cited by 20 · see citing works
Unique Metabolic Features of Adults Discordant for Indices of Insulin Resistance
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Self-citationSex-Associated Differences in Free Fatty Acid Flux of Obese Adolescents
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Cytokine Regulation of Lipolysis in Humans?
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Self-citationEffects of Estrogen and Testosterone on Resting Energy Expenditure in Older Men
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Self-citationEffects of Increased Free Fatty Acid Availability on Adipose Tissue Fatty Acid Storage in Men
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Sex- and Age-Related Metabolic Characteristics of Serum Free Fatty Acids in Healthy Chinese Adults
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What We Know and Do Not Know about Sex and Cardiac Disease
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Oxidative mechanisms at rest and during exercise
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Changes in substrate utilization rates during 40 min of walking within the Fatmax range
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Free fatty acid flux in African‐American and caucasian adults—effect of sex and race
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The role of the lipotoxicity in the pathogenesis of type 2 diabetes mellitus and obesity
Абдулкадирова, Ф. Р., As, A., Doskina, E. V., & Покровская, Р. А. (2014) · Obesity and metabolism · doi:10.14341/omet201428-12 · Cited by 7 · see citing works
- Authors
- Nielsen, S., Guo, Z., Albu, J. B., Klein, S., O’Brien, P. C., & Jensen, M. D.
- Affiliations
- Mayo Clinic (US)
- Columbia University (US)
- Washington University in St. Louis (US)
- Corresponding author
- Jensen, Michael D.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-04-01
- Volume
- 111
- Issue
- 7
- Pages
- 981-988
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC152581
- OpenAlex
- W2058262736
- Cited by
- 129
- References
- 43
- Citations by year
- 2025: 4 · 2024: 6 · 2023: 4 · 2022: 2 · 2021: 7 · 2020: 6 · 2019: 5 · 2018: 2 · 2017: 7 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 5 · 2012: 7
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- Sundhed og Sygdom, Det Frie Forskningsråd
- U.S. Public Health Service (DK-40484, DK-50456)
- Medical Research Council
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 40484, P30DK050456, DK50456, DK37948, R37DK040484, R01DK037948, 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 › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- resting energy expenditure, adipose tissue lipolysis, free fatty acid release, sex differences, obesity, palmitate, glucose release, respiratory quotient, fat-free mass
- MeSH terms
- Adipose Tissue, Adult, Basal Metabolism, Body Composition, Calorimetry, Fatty Acids, Nonesterified, Female, Glucose, Humans, Male, Middle Aged, Obesity, Sex Factors, Time Factors, Multivariate Analysis, Palmitic Acid
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