High-Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvement in Insulin Action in Obese Postmenopausal Women
Open accessAbstract
High-protein (HP) intake during weight loss (WL) therapy is often recommended because it reduces the loss of lean tissue mass. However, HP intake could have adverse effects on metabolic function, because protein ingestion reduces postprandial insulin sensitivity. In this study, we compared the effects of ∼10% WL with a hypocaloric diet containing 0.8 g protein/kg/day and a hypocaloric diet containing 1.2 g protein/kg/day on muscle insulin action in postmenopausal women with obesity. We found that HP intake reduced the WL-induced decline in lean tissue mass by ∼45%. However, HP intake also prevented the WL-induced improvements in muscle insulin signaling and insulin-stimulated glucose uptake, as well as the WL-induced adaptations in oxidative stress and cell structural biology pathways. Our data demonstrate that the protein content of a WL diet can have profound effects on metabolic function and underscore the importance of considering dietary macronutrient composition during WL therapy for people with obesity.
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Whether increasing protein intake during weight loss can limit the weight-loss-induced loss of fat-free mass is unclear because of conflicting results reported in the literature.
“Whether increasing protein intake during weight loss can limit the weight-loss-induced loss of fat-free mass is unclear because of conflicting results reported in the literature (54, 56, 96, 98, 101-108).”
From Preserving Healthy Muscle during Weight Loss (2017) · cites this paper as [106]
The Introduction says increased protein intake during weight loss helps preserve lean tissue mass, and the Results report about 45% less fat-free-mass loss in the high-protein group. The paper does not describe conflicting results in the literature as making that effect unclear; its Discussion instead questions the clinical importance of the small difference observed. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredHigh protein intake (1.2 g/kg/day) during weight loss might eliminate the beneficial effect of weight loss on insulin sensitivity in skeletal muscle.
“High protein intake (1.2 g of protein per kg per day) during weight loss might eliminate the beneficial effect of weight loss on insulin sensitivity in skeletal muscle258.”
From Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies (2018) · cites this paper as [258]
High protein intake could have adverse effects on metabolic function.
“and could have adverse effects on metabolic function”
From Preserving Healthy Muscle during Weight Loss (2017) · cites this paper as [106]
In a clinical trial, protein supplementation of a calorie-reduced weight loss diet prevents the improvement in insulin-mediated glucose disposal induced by 10% weight loss in women with obesity.
“Accordingly, in an elegantly designed clinical trial, protein supplementation of a calorie-reduced weight loss diet prevents the improvement in insulin-mediated glucose disposal induced by 10% weight loss in women with obesity (78).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [78]
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- Authors
- Smith, G. I., Yoshino, J., Kelly, S. C., Reeds, D. N., Okunade, A., Patterson, B. W., Klein, S., & Mittendorfer, B.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Mittendorfer, Bettina
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 17
- Issue
- 3
- Pages
- 849-861
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5113728
- OpenAlex
- W2530383994
- Cited by
- 111
- References
- 68
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 15 · 2023: 11 · 2022: 9 · 2021: 10 · 2020: 13 · 2019: 7 · 2018: 16 · 2017: 11
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (5p60dk020579-35, KL2TR000450, UL1TR000448)
- National Institute of General Medical Sciences (P41GM103422)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK094483, P60-DK-020579, P30DK092950, P30DK056341, P30DK020579)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- high-protein diet, weight loss, obesity, postmenopausal women, insulin signaling, insulin-stimulated glucose uptake, lean body mass, hypocaloric diet, macronutrient composition, oxidative stress, dietary protein
- MeSH terms
- Blood Glucose, Diet, Reducing, Dietary Proteins, Fatty Acids, Female, Gene Expression Regulation, Hormones, Humans, Inflammation, Insulin, Kinetics, Middle Aged, Mitochondria, Muscles, Obesity, Oxidation-Reduction, Biomarkers, Weight Loss, Postmenopause, Oxidative Stress, Palmitic Acid, Gene Expression Profiling, Lipogenesis, Metabolome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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