The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Effects of Moderate and Subsequent Progressive Weight Loss on Metabolic Function and Adipose Tissue Biology in Humans with Obesity
Open accessAbstract
SUMMARY Although 5%–10% weight loss is routinely recommended for people with obesity, the precise effects of 5% and further weight loss on metabolic health are unclear. We conducted a randomized controlled trial that evaluated the effects of 5.1±0.9% (n=19), 10.8±1.3% (n=9) and 16.4±2.1% (n=9) weight loss, and weight maintenance (n=14) on metabolic outcomes. Five percent weight loss improved adipose tissue, liver and muscle insulin sensitivity, and β-cell function, without a concomitant change in systemic or subcutaneous adipose tissue markers of inflammation. Additional weight loss further improved β-cell function and insulin sensitivity in muscle, and caused stepwise changes in adipose tissue mass, intrahepatic triglyceride content, and adipose tissue expression of genes involved in cholesterol flux, lipid synthesis, extracellular matrix remodeling and oxidative stress. These results demonstrate that moderate 5% weight loss improves metabolic function in multiple organs simultaneously, and progressive weight loss causes dose-dependent alterations in key adipose tissue biological pathways.
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“Weight loss clearly improves insulin sensitivity but the effects in different organ systems have individual variability depending upon the duration and extent of the metabolic dysregulation.”
From Effect of exercise training on insulin-stimulated glucose disposal: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [63]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“In addition, reductions in excess abnormal body fat ameliorate the systemic proinflammatory and prothrombotic milieu associated with obesity. 31”
From Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (2023) · cites this paper as [31]
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“A 10–15% loss may induce remission of T2D or MASLD.”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [71]
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“In general, insulin-mediated suppression of lipolysis in adipose tissue and suppression of HGP occur maximally at 5% to 8% weight loss 63, 64.”
From Effect of exercise training on insulin-stimulated glucose disposal: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [63]
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“Insulin-mediated glucose disposal in skeletal muscle continues to increase with additional weight loss 63.”
From Effect of exercise training on insulin-stimulated glucose disposal: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [63]
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“A weight loss of ≥ 5% represents the first clinically meaningful milestone, associated with improved metabolism, enhanced glucose metabolism and blood pressure.”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [71]
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“Interestingly, changes in hepatic and adipose tissue insulin sensitivity plateaued after 5 % weight loss, while insulin-mediated skeletal muscle glucose uptake as well as reduction of intrahepatic lipid content continued with progressive weight loss [45].”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [45]
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“While > 20% is typically required to reverse advanced metabolic or hepatic disease [71].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [71]
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Citations
Cites
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041 · cited 2×
“People with obesity and metabolic abnormalities often have concomitant systemic and adipose tissue ‘‘inflammation,’’ manifested by increased circulating inflammatory proteins and white blood cells, and increased subcutaneous adipose tissue macrophages, pro-inflammatory CD4 T-lymphocytes, and increased gene expression…”
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199 · cited 4×
“…inflammation, manifested by alterations in adipose tissue immune cell populations and increased gene expression of pro-inflammatory cytokines and chemokines, which cause systemic inflammation and insulin resistance (Berg and Scherer, 2005; Ferrante, 2007; Hotamisligil, 2006; Sun et al., 2013).”
InfluentialThe metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
Chen, X., Xiu, M., Xing, J., Yu, S., Min, D., & Guo, F. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479439 · Cited by 5,760
Kopelman, P. G. (2000) · Nature · doi:10.1038/35007508 · Cited by 4,795 · cited 2×
“…including insulin resistance, b cell dysfunction, nonalcoholic fatty liver disease, dyslipidemia, and hypertension, which are important risk factors for the development of serious medical complications such as type 2 diabetes and coronary heart disease (Klein et al., 2002; Kopelman, 2000).”
2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults
Jensen, M. D., Ryan, D. H., Apovian, C. M., Ard, J. D., Comuzzie, A. G., Donato, K. A., Hu, F. B., Hubbard, V. S., Jakicic, J. M., Kushner, R. F., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.11.004 · Cited by 4,058
Hotamisligil, G. S., Arner, P., Caro, J. F., Atkinson, R. L., & Spiegelman, B. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117936 · Cited by 3,543 · cited 2×
“Although a mechanistic relationship between inflammation andmetabolic dysfunction has been demonstrated in rodent models (Berg and Scherer, 2005; Brestoff and Artis, 2015; Ferrante, 2007; Hotamisligil, 2006; Hotamisligil et al., 1995; Sun et al., 2013), the importance of low-grade inflammation in the pathogenesis of o…”
Kim, H. J., Park, S. Y., Choi, Y. J., Han, S. J., Lee, K. W., & Kim, D. J. (2013) · Hormone Research in Paediatrics · doi:10.1159/000348848 · Cited by 3,061
Adipose Tissue, Inflammation, and Cardiovascular Disease
Berg, A. H., & Scherer, P. E. (2005) · Circulation Research · doi:10.1161/01.res.0000163635.62927.34 · Cited by 2,113 · cited 4×
“…inflammation, manifested by alterations in adipose tissue immune cell populations and increased gene expression of pro-inflammatory cytokines and chemokines, which cause systemic inflammation and insulin resistance (Berg and Scherer, 2005; Ferrante, 2007; Hotamisligil, 2006; Sun et al., 2013).”
InfluentialCorrect Homeostasis Model Assessment (HOMA) Evaluation Uses the Computer Program
Lévy, J., Matthews, D. R., & Hermans, M. P. (1998) · Diabetes Care · doi:10.2337/diacare.21.12.2191 · Cited by 2,023 · cited 2×
“Subjects with obesity had evidence of multi-organ insulin resistance (based on a homeostasis model assessment of insulin resistance score >2.0 [Levy et al., 1998] and results of a hyperinsulinemic-euglycemic clamp procedure conducted in conjunction with infusion of stable isotopically labeled…”
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Once-Weekly Semaglutide in Adults with Overweight or Obesity
Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2032183 · Cited by 5,205
“, prediabetes, hypertension, and obstructive sleep apnea).(1,20,21,27) In the semaglutide group, approximately 70% of participants achieved a weight loss of at least 10%, and approximately 50% achieved a weight loss of at least 15%.”
BackgroundMechanisms of NAFLD development and therapeutic strategies
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0104-9 · Cited by 4,354
Tirzepatide Once Weekly for the Treatment of Obesity
Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2206038 · Cited by 3,838
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
Lincoff, A. M., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., Hardt-Lindberg, S., Hovingh, G. K., Kahn, S. E., Kushner, R. F., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2307563 · Cited by 3,236
Adipose tissue inflammation and metabolic dysfunction in obesity
Kawai, T., Autieri, M. V., & Scalia, R. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00379.2020 · Cited by 1,947
Metadata
- Authors
- Magkos, F., Fraterrigo, G., Yoshino, J., Luecking, C., Kirbach, K., Kelly, S. C., de las Fuentes, L., He, S., Okunade, A. L., Patterson, B. W., & Klein, S.
- Affiliations
- Agency for Science, Technology and Research (SG)
- Washington University in St. Louis (US)
- Corresponding author
- Klein, Samuel
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 23
- Issue
- 4
- Pages
- 591-601
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4833627
- OpenAlex
- W2283809486
- Semantic Scholar
- 22c2c95f3eae678f67267c186f68d979ed5b03d6
- Cited by
- 886
- References
- 47
- Citations by year
- 2026: 83 · 2025: 92 · 2024: 95 · 2023: 90 · 2022: 108 · 2021: 97 · 2020: 93 · 2019: 79 · 2018: 64 · 2017: 57 · 2016: 26
- FWCI
- 70.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Longer Life Foundation
- Pershing Square Foundation
- National Institutes of Health (5p60dk020579-35, KL2TR000450, UL1TR000448)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK37948, DK20579, DK56341, R01DK104995, R01DK037948, DK104995, P60-DK-020579, P30DK092950, P30DK056341, P30DK020579)
- National Center for Research Resources (RR-024992, UL1RR024992)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- obesity, weight loss, weight maintenance, insulin sensitivity, beta-cell function, adipose tissue, liver, skeletal muscle, intrahepatic triglyceride, adipose tissue inflammation, cholesterol flux, lipogenesis, extracellular matrix remodeling, oxidative stress, dose-dependent effects
- MeSH terms
- Adipose Tissue, Adult, Female, Humans, Insulin, Insulin Resistance, Liver, Male, Middle Aged, Muscles, Obesity, Weight Loss, Insulin-Secreting Cells
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