Mechanistically different effects of fat and sugar on insulin resistance, hypertension, and gut microbiota in rats
Open accessAbstract
Insulin resistance (IR) and impaired glucose tolerance (IGT) are the first manifestations of diet-induced metabolic alterations leading to Type 2 diabetes, while hypertension is the deadliest risk factor of cardiovascular disease. The roles of dietary fat and fructose in the development of IR, IGT, and hypertension are controversial. We tested the long-term effects of an excess of fat or sucrose (fructose/glucose) on healthy male Wistar-Kyoto (WKY) rats. Fat affects IR and IGT earlier than fructose through low-grade systemic inflammation evidenced by liver inflammatory infiltration, increased levels of plasma IL-6, PGE 2, and reduced levels of protective short-chain fatty acids without triggering hypertension. Increased populations of gut Enterobacteriales and Escherichia coli may contribute to systemic inflammation through the generation of lipopolysaccharides. Unlike fat, fructose induces increased levels of diacylglycerols (lipid mediators of IR) in the liver, urine F 2-isoprostanes (markers of systemic oxidative stress), and uric acid, and triggers hypertension. Elevated populations of Enterobacteriales and E. coli were only detected in rats given an excess of fructose at the end of the study. Dietary fat and fructose trigger IR and IGT in clearly differentiated ways in WKY rats: early low-grade inflammation and late direct lipid toxicity, respectively; gut microbiota plays a role mainly in fat-induced IR, and hypertension is independent of inflammation-mediated IR. The results provide evidence that suggests that the combination of fat and sugar is potentially more harmful than fat or sugar alone when taken in excess.
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Miloslavsky, D. К., Koval, S. M., Snegurska, I. A., Божко, В. В., Резник, Л. А., & Schenyavska, Е. N. (2021) · HYPERTENSION · doi:10.22141/2224-1485.14.4.2021.240255 · Cited by 1 · see citing works
Fighting Fire with Fire: Impact of Sugary Diets on Metabolically Deranged Mice
Glendinning, J. I., & Williams, N. (2024) · Nutrients · doi:10.3390/nu17010100 · Cited by 1 · see citing works
Bovolini, A., Garcia, J., Silva, A. F., Andrade, M. A., & Duarte, J. A. (2020) · Nutrition · doi:10.1016/j.nut.2020.110838 · Cited by 1 · see citing works
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Trikha, S. R. J., Wrigley, S. D., Gentile, C. L., & Weir, T. L. (2019) · Elsevier eBooks · doi:10.1016/b978-0-08-100596-5.22883-7
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Tănase, D. M., Leustean, A. M., & Gosav, E. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821039-0.00005-8
Introduction to gut microbiome and epigenetics
Oshinjo, A. M., Michael, O. S., Adedayo, L. D., Adetunji, C. O., Bamidele, O., Adetunji, J. B., Morakinyo, A., Akinwale, E. O., Ajayi, O. O., Awobajo, F. O., et al. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-91190-0.00009-6
Miralles‐Pérez, B., Ramos‐Romero, S., Charpentier, M. J., Sánchez‐Martos, V., Fortuño-Mar, À., Ponomarenko, J. V., Amézqueta, S., Piñol‐Piñol, D., Zhang, X., Torres, J. L., et al. (2025) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.70230
Self-citationMetabolic factors, gut microbiota, and cognitive performance: Mendelian randomization analysis
Yu, E., Zhang, Y., Chen, J., Peng, B., & Xin, J. (2025) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823251405877
- Authors
- Ramos-Romero, S., Hereu, M., Atienza, L., Casas, J., Jáuregui, O., Amézqueta, S., Dasilva, G., Medina, I., Nogués, M. R., Romeu, M., & Torres, J. L.
- Affiliations
- Institute of Advanced Chemistry of Catalonia, Consejo Superior de Investigaciones Científicas (IQAC-CSIC), Barcelona, Spain
- Consejo Superior de Investigaciones Científicas (ES)
- Department of Pathology, Puerta del Mar University Hospital, Cádiz, Spain
- Centres Científics i Tecnològics de la Universitat de Barcelona (ES)
- Universitat de Barcelona (ES)
- Instituto de Investigacións Mariñas (ES)
- Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain
- Universitat Rovira i Virgili (ES)
- ORCID
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2018-06-01
- Volume
- 314
- Issue
- 6
- Pages
- E552-E563
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2781872300
- Cited by
- 52
- References
- 51
- Citations by year
- 2025: 7 · 2024: 6 · 2023: 3 · 2022: 6 · 2021: 8 · 2020: 9 · 2019: 7 · 2018: 6
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Rovira & Virgili repository (submittedVersion, cc-by)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, other-oa)
- Funders
- Spanish Ministry of Economy and Competitiveness (AGL2013-49079-C2-1, 2-R, BES2014-068592)
- Consejo Superior de Investigaciones Científicas
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- insulin resistance, hypertension, gut microbiota, dietary fat, fructose, sucrose, impaired glucose tolerance, low-grade inflammation, diacylglycerol, oxidative stress, uric acid, Enterobacterales, Escherichia coli, lipopolysaccharide, short-chain fatty acids, type 2 diabetes, Wistar-Kyoto rats
- MeSH terms
- Gastrointestinal Microbiome, Dietary Sugars, Animals, Blood Pressure, Dietary Fats, Drinking Behavior, Energy Metabolism, Hypertension, Insulin Resistance, Male, Rats, Inbred WKY, Signal Transduction, Weight Gain, Rats
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