Low-Fat by Formulation, Not by Benefit: A Purified Low-Fat Diet Is Associated with Gut–Liver–Kidney Alterations in Rats
8 affiliations
- 1Institute of Pharmacology & Experimental Therapeutics Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- 2Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
- 3CIBB—Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004–504 Coimbra, Portugal
- 4CACC—Clinical Academic Center of Coimbra, 3004-531 Coimbra, Portugal
- 5CBQF—Centro de Biotecnologia e Química Fina—Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
- 6Nephrology Department, Unidade Local de Saúde de Coimbra, 3000-076 Coimbra, Portugal
- 7FFUC—Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
- 8CERES—Chemical Engineering and Renewable Resources for Sustainability, Department of Chemical Engineering, University of Coimbra, 3030-790 Coimbra, Portugal
Abstract
Background/Objectives: “Low-fat” claims are defined by a fat threshold, with no requirements regarding the nutrients replacing fat. Reformulation often relies on refined starches and free sugars at the expense of dietary fiber. Thus, a low-fat (LF) product is not necessarily of good carbohydrate quality, a dimension that macronutrient-based classification fails to capture. Whether LF-derived poor carbohydrate quality is associated with organ-specific alterations across the gut–liver–kidney axis remains unknown. Methods: Male Wistar rats were fed for 24 weeks a purified LF diet, its ingredient-matched purified high-fat, high-sucrose counterpart (HF), or a whole-grain Chow reference of similar energy density. Carbohydrate quality was assessed using the carbohydrate-to-dietary fiber-to-free sugars ratio. Body weight and adiposity, glucose homeostasis, gut fermentation, and hepatic and renal functional and structural parameters were evaluated. Results: Only Chow met the 10:1:1 carbohydrate quality criterion. At a caloric intake that did not exceed that of Chow, LF feeding was associated with increased body weight, adipocyte hypertrophy, impaired glucose tolerance and postprandial hyperinsulinemia. Fecal short-chain fatty acids (SCFAs) and branched SCFAs declined, consistent with a reduction in colonic fermentative output. Chronic LF exposure was additionally associated with hepatic and renal lipid accumulation, normoglycemic glycosuria, and podocyte structural alterations. Conclusions: A purified low-fat diet was associated with the same spectrum of gut, liver and kidney alterations as its high-fat counterpart, without excess caloric intake. These findings support an important role for nutrient sources and carbohydrate quality in shaping metabolic health beyond dietary fat content or caloric load alone.
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BibTeX
@article{vieira2026lowfat,
title = {{Low-Fat by Formulation, Not by Benefit: A Purified Low-Fat Diet Is Associated with Gut–Liver–Kidney Alterations in Rats}},
author = {Pedro Vieira and Gonçalo Ferreira and Filipa Carvalho and Carolina Ferreira and André Alves and Pedro Gomes and Tânia Martins-Marques and Tânia Ribeiro and Pedro Castro and Mónica Zuzarte and Henrique Girão and Manuela Pintado and Lígia Salgueiro and Flávio Reis and Sofia Viana},
journal = {Nutrients},
year = {2026},
month = nov,
doi = {10.3390/nu18213718},
url = {https://www.mdpi.com/2072-6643/18/21/3718},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Low-Fat by Formulation, Not by Benefit: A Purified Low-Fat Diet Is Associated with Gut–Liver–Kidney Alterations in Rats
AU - Pedro Vieira
AU - Gonçalo Ferreira
AU - Filipa Carvalho
AU - Carolina Ferreira
AU - André Alves
AU - Pedro Gomes
AU - Tânia Martins-Marques
AU - Tânia Ribeiro
AU - Pedro Castro
AU - Mónica Zuzarte
AU - Henrique Girão
AU - Manuela Pintado
AU - Lígia Salgueiro
AU - Flávio Reis
AU - Sofia Viana
PY - 2026
DA - 2026/11/09
JO - Nutrients
DO - 10.3390/nu18213718
UR - https://www.mdpi.com/2072-6643/18/21/3718
AB - Background/Objectives: “Low-fat” claims are defined by a fat threshold, with no requirements regarding the nutrients replacing fat. Reformulation often relies on refined starches and free sugars at the expense of dietary fiber. Thus, a low-fat (LF) product is not necessarily of good carbohydrate quality, a dimension that macronutrient-based classification fails to capture. Whether LF-derived poor carbohydrate quality is associated with organ-specific alterations across the gut–liver–kidney axis remains unknown. Methods: Male Wistar rats were fed for 24 weeks a purified LF diet, its ingredient-matched purified high-fat, high-sucrose counterpart (HF), or a whole-grain Chow reference of similar energy density. Carbohydrate quality was assessed using the carbohydrate-to-dietary fiber-to-free sugars ratio. Body weight and adiposity, glucose homeostasis, gut fermentation, and hepatic and renal functional and structural parameters were evaluated. Results: Only Chow met the 10:1:1 carbohydrate quality criterion. At a caloric intake that did not exceed that of Chow, LF feeding was associated with increased body weight, adipocyte hypertrophy, impaired glucose tolerance and postprandial hyperinsulinemia. Fecal short-chain fatty acids (SCFAs) and branched SCFAs declined, consistent with a reduction in colonic fermentative output. Chronic LF exposure was additionally associated with hepatic and renal lipid accumulation, normoglycemic glycosuria, and podocyte structural alterations. Conclusions: A purified low-fat diet was associated with the same spectrum of gut, liver and kidney alterations as its high-fat counterpart, without excess caloric intake. These findings support an important role for nutrient sources and carbohydrate quality in shaping metabolic health beyond dietary fat content or caloric load alone.
SN - 2072-6643
ER -